Cosmetics
A cosmetic preparation with hyaluronic acid and a chelating agent addresses the issue of reduced moisturization by compacting hyaluronic acid, ensuring effective moisture retention through cation capture and swelling.
Patent Information
- Application Number
- JP2022580559
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-02-10
- Filing Date
- 2022-01-28
- Publication Date
- 2026-02-10
- Estimated Expiration
- 2042-01-28
AI Technical Summary
Hyaluronic acid's moisturizing properties are compromised when compacted by neutralizing its carboxyl groups with salts, leading to reduced water-holding capacity and insufficient moisturization.
A cosmetic preparation comprising a first agent with hyaluronic acid and a salt, and a second agent with a chelating agent that captures cations neutralizing the carboxyl groups, allowing hyaluronic acid to swell and retain moisture.
Ensures sufficient moisturizing properties by enabling hyaluronic acid to fully exhibit its water-holding ability, even when compacted, through the use of a chelating agent to neutralize the electrostatic shielding effect.
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Abstract
Description
[Technical Field]
[0001] The present disclosure relates to cosmetics. [Background technology]
[0002] For example, hyaluronic acid, which has a moisturizing function, is 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, which are nanoparticles formed from either polylactic acid, polyglycolic acid, or lactic acid / glycolic acid copolymer and have hyaluronic acid loaded on at least one of the interior and surface of the nanoparticles.
[0004] Patent Document 2 discloses an external skin preparation containing composite nanoparticles that contain (A) hyaluronic acid and (B) an amphoteric compound and have a particle size of 100 nm or less.
[0005] Unpublished Patent Document 3 discloses a cosmetic preparation containing an aqueous medium and hyaluronic acid particles dispersed in the aqueous medium, the average particle size of the hyaluronic acid particles being 200 nm or less. [Prior art documents] [Patent documents]
[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2010-150151 [Patent Document 2] International Publication No. 2018 / 182003 [Patent Document 3] PCT / JP2020 / 031318 Summary of the Invention [Problem to be solved by the invention]
[0007] Hyaluronic acid has a negative charge due to the presence of carboxyl groups. Due to electrostatic repulsion caused by this negative charge, hyaluronic acid generally spreads out in a thread-like shape.
[0008] Compacted hyaluronic acid as described in Patent Documents 1 and 2 is more likely to remain in, for example, skin grooves or pores than hyaluronic acid spread out like threads. However, the content of hyaluronic acid in the particles described in Patent Document 1 is as low as about 3% by mass, and the content of hyaluronic acid in the particles described in Patent Document 2 is also limited to 50% by mass or less, so there are cases where sufficient moisturizing properties cannot be ensured.
[0009] As described in Patent Document 3, the researchers of the present applicant have discovered that by utilizing the electrostatic shielding effect of electrolytes such as sodium chloride, the negative charge based on the carboxyl groups of hyaluronic acid is apparently neutralized, and hydrogen bonds based on hydroxyl groups in hyaluronic acid, which exert an attractive effect, are made dominant, thereby suppressing the spreading of hyaluronic acid and making it possible to compact the hyaluronic acid.
[0010] However, when hyaluronic acid is compacted using the technology described in Patent Document 3, the carboxyl groups of hyaluronic acid are neutralized by electrolytes such as sodium chloride, resulting in a decrease in the amount of water it can hold (hydration amount), and therefore, it may not be possible to ensure the sufficient moisturizing properties that hyaluronic acid itself possesses.
[0011] Therefore, the subject of the present disclosure is to provide a cosmetic preparation that can ensure sufficient moisturizing properties even when using hyaluronic acid that has been compacted by neutralizing the carboxyl groups of hyaluronic acid with a salt. [Means for solving the problem]
[0012] <Aspect 1> A first agent containing at least one salt selected from the group consisting of inorganic salts and organic acid salts, and hyaluronic acid; and a second agent for swelling the hyaluronic acid, the second agent including a chelating agent; Cosmetics. <Aspect 2> The cosmetic preparation according to aspect 1, wherein the volume of hyaluronic acid in the first agent increases when the second agent is applied to the first agent. <Aspect 3> 3. The cosmetic preparation according to claim 1, wherein the hyaluronic acid is contained in an amount of 0.005% by mass or more relative to the total amount of the first agent. <Aspect 4> A cosmetic preparation according to any one of Aspects 1 to 3, wherein the cation that constitutes the salt is a metal ion. <Aspect 5> The chelating agent is selected from the group consisting of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetic acid, trisodium ethylenediaminetetraacetic acid, nitrilotriacetic acid, sodium nitrilotriacetate, ammonium nitrilotriacetate, hydroxyethylethylenediaminetriacetic acid, sodium hydroxyethylethylenediaminetriacetate, pentetic acid, pentasodium pentetate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, imidisuccinic acid, tetrasodium imidisuccinate, ethylenediaminedisuccinic acid, trisodium ethylenediaminedisuccinate, hydroxyethyliminodiacetic acid, disodium hydroxyethyliminodiacetate, iminodisuccinic acid, tetrasodium iminodisuccinate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, methylglycinediacetic acid, trisodium methylglycinediacetate, hydroxyiminodisuccinic acid, tetrasodium hydroxyiminodisuccinate, and L-asparagine. 5. The cosmetic preparation according to any one of Aspects 1 to 4, wherein the acid is at least one selected from the group consisting of tetrasodium L-aspartate diacetate, glutamic acid diacetate, tetrasodium glutamic acid diacetate, propanediaminetetraacetic acid, diammonium ethylenediaminetetraacetate, 1,3-diamino-2-hydroxypropane-tetraacetic acid, 1,3-diamino-2-hydroxypropane-tetraacetic acid, N,N-bis(2-hydroxyethyl)glycine, glycoletherdiaminetetraacetic acid, dicarboxymethylglutamic acid, tetrasodium dicarboxymethylglutamate, diethylenetriaminepentaacetic acid, hexametaphosphoric acid, sodium hexametaphosphate, nitrilotris(methylenephosphonic acid), potassium nitrilotris(methylenephosphonate), 2-phosphonobutane-1,2,4-tricarboxylic acid, ethylenediaminetetramethylenephosphonic acid, pentasodium ethylenediaminetetramethylenephosphonate, phytic acid, and citric acid. <Aspect 6> A cosmetic preparation according to any one of Aspects 1 to 5, wherein the weight-average molecular weight of the hyaluronic acid is 10,000,000 or less. <Aspect 7> A beauty method using the cosmetic preparation according to any one of aspects 1 to 6, comprising: After applying the first agent to the body surface or body hair, the second agent is applied to the surface to which the first agent has been applied. Beauty method. [Effects of the Invention]
[0013] According to the present disclosure, it is possible to provide a cosmetic preparation that can ensure sufficient moisturizing properties even when using hyaluronic acid that has been compacted by neutralizing the carboxyl groups of hyaluronic acid with a salt. [Brief explanation of the drawings]
[0014] [Figure 1] This is a graph showing the relationship between the amount (mol) of chelating agent (HMP) per 100 mol of salt (MgCl2) and the swelling of compacted hyaluronic acid. [Figure 2] 1 is a graph showing the relationship between the amount (mol) of substance of a chelating agent (HMP) relative to 100 mol of salt (NaCl) and the swelling of compacted hyaluronic acid. [Figure 3] 1 is a graph showing the change in moisture content of the stratum corneum before and after application of various test samples to the skin. [Figure 4] 1 is a graph showing the change in skin texture count before and after application of various test samples to the skin. [Figure 5] 1 is a graph showing the Z-average particle size and ionic strength of hyaluronic acid particles prepared using sodium chloride. [Figure 6] 1 is a graph showing the Z-average particle size and ionic strength of hyaluronic acid particles in compositions with various hyaluronic acid concentrations prepared using sodium chloride. [Figure 7] 1 is a graph showing the Z-average particle size and ionic strength of hyaluronic acid particles in compositions prepared using sodium chloride with hyaluronic acid concentrations of 0.4% by mass and 0.5% by mass. [Figure 8] 1 is a graph showing the relationship between the Z-average particle size of hyaluronic acid particles and moisturizing performance. [Figure 9] 1 is a graph showing the Z-average particle size and ionic strength of hyaluronic acid particles prepared using a citrate buffer solution. [Figure 10] 1 is a graph showing the Z-average particle size of hyaluronic acid particles with the addition of urea. DETAILED DESCRIPTION OF THE INVENTION
[0015] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present disclosure is not limited to the following embodiments, and various modifications can be made within the scope of the present invention.
[0016] The cosmetic preparation of the present disclosure comprises a first agent containing at least one salt selected from the group consisting of inorganic salts and organic acid salts, and hyaluronic acid, and a second agent containing a chelating agent for swelling the hyaluronic acid.
[0017] Although not limited by the principle, the principle of action that the cosmetic preparation of the present disclosure can ensure sufficient moisturizing property even when using hyaluronic acid that is compacted by neutralizing the carboxyl group of hyaluronic acid with salt is as follows.Here, in the present disclosure, "compacted" means that compared with the structure of one molecule of hyaluronic acid or a plurality of hyaluronic acid molecules entangled in the state that salt is not added, it can be said that it is contracted.Typically, when salt is included together with hyaluronic acid, it can be said that the structure of one molecule of hyaluronic acid or a plurality of hyaluronic acid molecules entangled in the state is contracted.
[0018] Hyaluronic acid generally has a negative charge due to the existence of carboxyl group.Because of the electrostatic repulsion based on this negative charge, for example, hyaluronic acid molecules tend to spread like threads, and are difficult to compact.Therefore, in order to contract the structure of hyaluronic acid molecules and make them compact, as in Patent Documents 1 and 2, it is necessary to use a nanometer-order support material that can support hyaluronic acid molecules.As a result, the content ratio of hyaluronic acid in compacted structures is limited.
[0019] On the other hand, according to the technology of Patent Document 3, by utilizing the electrostatic shielding effect of electrolyte such as sodium chloride, the negative charge of hyaluronic acid is apparently neutralized, and hydrogen bond is made dominant, so that the spreading of hyaluronic acid molecules is suppressed, and even hyaluronic acid molecules can be made compact by themselves.The compacted hyaluronic acid structure prepared by the technology of Patent Document 3 can be prepared without using the above-mentioned supporting material, so the content ratio of hyaluronic acid in this structure can be theoretically 100% by mass.
[0020] However, when a cosmetic containing the compacted hyaluronic acid structure prepared in this manner is applied to the skin or body hair, the carboxyl groups of the hyaluronic acid continue to be neutralized by electrolytes such as sodium chloride (e.g., metal ions such as sodium ions), and it is thought that the water-holding ability (hydration ability) of the carboxyl groups cannot be fully exerted.
[0021] On the other hand, the cosmetic composition of the present disclosure includes a second agent containing a chelating agent. Such a second agent can capture components (e.g., metal ions such as sodium ions) that neutralize the negative charge of carboxyl groups. Therefore, it is believed that when hyaluronic acid compacted with a salt is applied to skin or body hair, and then a second agent containing a chelating agent is applied, it can capture cations such as sodium ions that neutralized the carboxyl groups. As a result, the carboxyl groups in hyaluronic acid are able to fully exhibit their water-holding ability (hydration ability), thereby providing good moisturizing properties to skin or body hair.
[0022] Here, it can be indirectly confirmed from, for example, Figures 1 and 2 that the second agent containing chelating agent captures the cations such as sodium ion that neutralize carboxyl group.When chelating agent is mixed into the solution that contains the hyaluronic acid that is compacted by using salt, the compacted hyaluronic acid swells.That is to say, it is considered that the cations such as sodium ion are captured by the addition of chelating agent, and the electrostatic shielding effect is reduced, resulting in this swelling phenomenon.
[0023] In addition, because the chelating agent itself has metal ions, when the amount of chelating agent increases, hyaluronic acid can be compacted again.The optimal amount of chelating agent varies depending on the type of chelating agent, but if the chelating agent is blended in the second agent so that the hyaluronic acid that is compacted with salt can swell, the cosmetic composition of the present disclosure can provide good moisturizing properties regardless of the chelating agent.
[0024] Hyaluronic acid compacted with salt can also be swollen with urea, as shown in Figure 10. However, swelling with urea is not achieved by reducing the electrostatic shielding effect, but by breaking the hydrogen bonds resulting from compaction.
[0025] Cosmetics The cosmetic composition of the present disclosure comprises a first agent and a second agent.
[0026] <First agent> The first agent of the present disclosure contains at least one salt selected from the group consisting of inorganic salts and organic acid salts, and hyaluronic acid.
[0027] (salt) The salt that can be incorporated into the first agent of the present disclosure is not particularly limited as long as it can apparently neutralize the negative charge of hyaluronic acid. Examples of such salts include at least one salt selected from inorganic salts and organic acid salts. Considering use as a cosmetic, among inorganic salts and organic acid salts, salts that are less likely to have adverse effects on skin or body hair are preferred. Here, "inorganic salt" refers to a salt composed solely of inorganic components, which 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 the first agent in the form of salt-derived ions. Therefore, in the present disclosure, for example, a "first agent containing a salt" is intended to include salts in such ionic form. Furthermore, ionic surfactants are not included in the "salt" of the present disclosure.
[0028] 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. These salts can be used alone or in combination.
[0029] Examples of organic acid salts include citrates, acetates, lactates, tartrates, succinates, malates, glycolates, salicylates, and pyrrolidone carboxylic acid salts. 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 carboxylic acid bound to metal ions such as sodium ions, potassium ions, calcium ions, magnesium ions, and aluminum ions. These salts can be used alone or in combination.
[0030] From the viewpoint of the cation capture ability of the chelating agent contained in the second agent described below, the cations constituting the salt are preferably metal ions, and more preferably divalent or higher valent metal ions.
[0031] The amount of the salt in the first agent is not particularly limited and can be appropriately selected according to the degree of compaction of hyaluronic acid.For example, this amount can be 0.10% by mass or more, 0.20% by mass or more, 0.30% by mass or more, 0.40% by mass or more, or 0.50% by mass or more, and can be 5.0% by mass or less, 4.0% by mass or less, 3.0% by mass or less, 2.0% by mass or less, 1.9% by mass or less, 1.8% by mass or less, 1.7% by mass or less, 1.6% by mass or less, or 1.5% by mass or less, based on the total amount of the first agent.
[0032] The amount of salt in the first agent can also be defined as the ionic strength of the salt, which can be, for example, 0.01 or more, 0.03 or more, or 0.05 or more, and 5.0 or less, 4.0 or less, 3.0 or less, 2.0 or less, or 1.0 or less.
[0033] Here, for example, when preparing the first agent by adding a salt to a buffer solution, the amount of salt or ionic strength 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.
[0034] (Hyaluronic acid) There are no particular limitations on the hyaluronic acid that can be incorporated into the first agent of the present disclosure. Generally, hyaluronic acid refers to a linear polymer in which N-acetyl-D-glucosamine residues and D-glucuronic acid residues are alternately bonded, and such hyaluronic acid can be obtained, for example, by isolation and extraction from chicken combs or other animal tissues, or by fermentation using microorganisms such as Streptococcus.
[0035] Hyaluronic acid may be its derivative, and for example, as the derivative of hyaluronic acid, metal salt of hyaluronic acid such as sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, calcium hyaluronate, aluminum hyaluronate, etc., or the hyaluronic acid derivative obtained by etherifying, esterifying, amidating, acetylating, acetalizing, or ketalizing the hydroxyl group, carboxyl group, etc. of hyaluronic acid can be used.Here, "hyaluronic acid" in the present disclosure can include the concept of hyaluronic acid and its derivative.
[0036] The weight-average molecular weight of hyaluronic acid is not particularly limited, and can be, for example, 10,000,000 or less.From the viewpoint of the moisture retention performance of hyaluronic acid and compacting of hyaluronic acid, the weight-average molecular weight of hyaluronic acid 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, and can be 10,000,000 or less, 8,000,000 or less, 5,000,000 or less, 3,000,000 or less, 2,000,000 or less, or 1,500,000 or less. Here, the weight average molecular weight refers to the weight average molecular weight in terms of polystyrene measured by gel permeation chromatography.
[0037] In some embodiments, the hyaluronic acid of the present disclosure can be in the form of particles with an average particle diameter of 200 nm or less.Hyaluronic acid in this form is more likely to penetrate into the skin or body hair, for example, through the stratum corneum or pores of the skin, and can easily penetrate into the interior of the skin non-invasively.In general, hyaluronic acid with a relatively low molecular weight of less than 500 weight-average molecular weight is thought to be more likely to penetrate into the skin or body hair without being microparticulated.However, such low molecular weight hyaluronic acid is less likely to remain inside the skin or body hair, and its moisture retention ability is inferior to that of high molecular weight hyaluronic acid, so it may be difficult to maintain the moisturizing effect inside the skin or body hair for a long period of time.On the other hand, the hyaluronic acid particles of the present disclosure can be prepared using hyaluronic acid with a weight-average molecular weight of 500 or more, and can contain a high concentration of such hyaluronic acid in the particles.As a result, the obtained hyaluronic acid particles are more likely to remain inside the skin or body hair, and can maintain the moisturizing effect inside the skin or body hair for a long period of time.
[0038] Hyaluronic acid and its derivatives can be used alone or in combination of two or more. The molecular weights of the hyaluronic acid and its derivatives used may be the same or different.
[0039] Commercially available hyaluronic acid may be used. Examples of commercially available hyaluronic acid include 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.).
[0040] It is believed that the hyaluronic acid contained in the first agent of the present disclosure shrinks due to the electrostatic shielding effect of the salt and the action of hydrogen bonds, and assumes a form in which hyaluronic acid molecules are aggregated singly or in groups entangled together (this form may be referred to as a "hyaluronic acid aggregate / shrinkage product"). Hyaluronic acid in this form can be prepared without using a support material such as those described in Patent Documents 1 and 2, so the content of hyaluronic acid in the hyaluronic acid aggregate / shrinkage product can theoretically be 100% by mass. In other words, the hyaluronic acid aggregate / shrinkage product of the present disclosure can be composed solely of hyaluronic acid molecules as the polymer component.
[0041] However, the hyaluronic acid aggregate / contraction product of the present disclosure may contain other polymer components other than hyaluronic acid, as long as it does not cause problems with moisturizing performance, etc. The content ratio of other polymer components can be, for example, 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 amount of polymers contained in the hyaluronic acid aggregate / contraction product. That is, in the present disclosure, the term "hyaluronic acid aggregate / contraction product" refers to a substance that contains a high amount of hyaluronic acid components, and does not include particles with a hyaluronic acid component ratio of 50% by mass or less, as described in Patent Documents 1 and 2. Here, the content ratio of hyaluronic acid in the hyaluronic acid aggregate / contraction product can be measured, for example, using ELISA.
[0042] In some embodiments, the hyaluronic acid aggregates and contractions can be made into a thread-like particle form (sometimes referred to as "hyaluronic acid particles") that can be measured by dynamic light scattering, for example, by adjusting the amount of salt added. The penetration of hyaluronic acid particles into skin or body hair varies from person to person, and can vary depending on the state of the stratum corneum, the state of hair, the number or size of pores, etc., but as long as the particles have an average particle diameter of 200 nm or less, they can penetrate into most skin or body hair. From the viewpoint of the penetration into skin or body hair, ease of particle preparation, etc., the average particle diameter of hyaluronic acid particles can be, for example, 150 nm or less, 120 nm or less, or 100 nm or less, or 10 nm or more, 30 nm or more, or 50 nm or more. Here, the average particle diameter refers to the Z-average particle diameter of hyaluronic acid particles optically measured by dynamic light scattering, assuming that the particle shape of hyaluronic acid particles is spherical. The average particle size can be measured, for example, using a Zetasizer (Malvern Panalytical) or a dynamic light scattering photometer DLS-8000 (Otsuka Electronics). These measuring devices can be selected appropriately based on the overlap concentration of each hyaluronic acid. For example, if the overlap concentration is less than the overlap concentration, the dynamic light scattering photometer DLS-8000 can be used, and if the overlap concentration is equal to or greater than the overlap concentration, the Zetasizer can be used. The overlap concentration can be calculated, for example, by confocal fluorescence recovery after bleaching (confocal-FRAP).
[0043] Hyaluronic acid particles with an average particle size of 200 nm or less can penetrate into the skin or hair, but due to their small particle size, they are unlikely to remain inside the skin or hair.The cosmetic preparation of the present disclosure can apply a second agent containing a chelating agent to such hyaluronic acid particles to swell these particles.In other words, after the hyaluronic acid penetrates into the skin or hair, the second agent can be applied to swell the hyaluronic acid inside the skin or hair, so that the hyaluronic acid can remain inside the skin or hair.As a result, the moisturizing effect inside the skin or hair can be maintained for a longer period of time.
[0044] The content of hyaluronic acid in the first agent can be, for example, from the viewpoint 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 first agent, and as described above, the hyaluronic acid contained in the first agent of the present disclosure has a high content of hyaluronic acid in the hyaluronic acid aggregate / contraction product, and due to the action of the chelating agent of the second agent, has excellent hydration ability based on the carboxyl group in the hyaluronic acid, so that even if the content of hyaluronic acid in the first agent is relatively low, sufficient moisturizing effect can be exhibited.
[0045] (aqueous medium) The first agent 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.
[0046] 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.
[0047] 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 irritation to the skin or body hair.
[0048] <Second agent> The second agent of the present disclosure contains a chelating agent and can swell the above-mentioned hyaluronic acid. Being able to swell hyaluronic acid, in other words, means that the chelating agent is contained in the second agent in an amount that can swell hyaluronic acid, as shown in Figure 1 or Figure 2. If the chelating agent is contained in the second agent in a proportion that can swell hyaluronic acid, it can be said that the chelating agent can sufficiently capture the cations that neutralize the carboxyl groups in hyaluronic acid. The carboxyl groups in hyaluronic acid from which the cations have been dissociated can fully exhibit their water-holding ability (hydration ability), and since the swollen hyaluronic acid has increased water-holding capacity compared to compacted hyaluronic acid, such hyaluronic acid can provide good moisturizing properties to the skin.
[0049] Swelling of hyaluronic acid means that the volume of hyaluronic acid in the first agent increases when the second agent is applied to the first agent, and this increase in the volume of hyaluronic acid can be evaluated by the ratio based on particle size (sometimes referred to as the "particle size ratio") or the ratio based on partial specific volume (sometimes referred to as the "partial specific volume ratio").
[0050] The particle size ratio can be greater than 1.00, 1.10 or greater, 1.20 or greater, or 1.30 or greater. There is no particular upper limit to the particle size ratio, but it can be, for example, 3.00 or less, 2.50 or less, 2.00 or less, or 1.80 or less. Here, the "particle size ratio" refers to a value calculated by the following formula 1: Particle size ratio = average particle size of hyaluronic acid particles in the first agent containing a specified amount of chelating agent / average particle size of hyaluronic acid particles in the first agent containing no chelating agent ...Equation 1
[0051] The partial specific volume ratio can be more than 1.00, 1.01 or more, or 1.02 or more. There is no particular limitation on the upper limit of the partial specific volume ratio, but it can be, for example, 1.20 or less, 1.15 or less, or 1.10 or less. Here, "partial specific volume" refers to the change in total volume (cm) when 1 g of hyaluronic acid is dissolved in an infinite solvent at constant temperature, pressure, and the concentrations of all other components. 3 / g), and the "partial specific volume ratio" means a value calculated by the following formula 2, and the "partial specific volume ratio" means a value calculated by the following formula 3:
number
[0052] Partial specific volume ratio = Partial specific volume of hyaluronic acid in the first agent containing a specified amount of chelating agent / Partial specific volume of hyaluronic acid in the first agent containing no chelating agent …Equation 3
[0053] (chelating agent) There are no particular restrictions on the chelating agent that can be incorporated into the second agent of the present disclosure, as long as it is a chelating agent that can capture cations that electrostatically shield the negative charge of the carboxyl group of hyaluronic acid and swell the hyaluronic acid. Examples of such chelating agents include ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetate, trisodium ethylenediaminetetraacetate, nitrilotriacetic acid, sodium nitrilotriacetate, ammonium nitrilotriacetate, hydroxyethylethylenediaminetriacetic acid, sodium hydroxyethylethylenediaminetriacetate, pentetic acid, pentasodium pentetate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, imidisuccinic acid, tetrasodium imidisuccinate, ethylenediaminedisuccinic acid, trisodium ethylenediaminedisuccinate, hydroxyethyliminodiacetic acid, disodium hydroxyethyliminodiacetate, iminodisuccinic acid, tetrasodium iminodisuccinate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, methylglycinediacetic acid, trisodium methylglycinediacetate, hydroxyiminodisuccinic acid, hydroxyiminodisuccinic acid, Examples of suitable chelating agents include tetrasodium succinate, L-aspartic acid diacetate, tetrasodium L-aspartic acid diacetate, glutamic acid diacetate, tetrasodium glutamic acid diacetate, propanediaminetetraacetic acid, diammonium ethylenediaminetetraacetate, 1,3-diamino-2-hydroxypropanetetraacetic acid, 1,3-diamino-2-hydroxypropanetetraacetic acid, N,N-bis(2-hydroxyethyl)glycine, glycoletherdiaminetetraacetic acid, dicarboxymethylglutamic acid, tetrasodium dicarboxymethylglutamate, diethylenetriaminepentaacetic acid, hexametaphosphoric acid, sodium hexametaphosphate, nitrilotris(methylenephosphonic acid), potassium nitrilotris(methylenephosphonic acid), 2-phosphonobutane-1,2,4-tricarboxylic acid, ethylenediaminetetramethylenephosphonic acid, pentasodium ethylenediaminetetramethylenephosphonate, phytic acid, and citric acid. The chelating agents may be used alone or in combination.Among these, disodium ethylenediaminetetraacetate (EDTA), hydroxyethyliminodiacetic acid (HIDA), diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid, phytic acid, and sodium hexametaphosphate (HMP) are preferred from the viewpoint of cation capture and the moisturizing effect of hyaluronic acid resulting from this cation capture.
[0054] The amount of chelating agent in the second agent can be appropriately set within a range that increases the particle size ratio or partial specific volume ratio of hyaluronic acid, depending on the type and amount of hyaluronic acid or salt in the first agent and the type of chelating agent.
[0055] For example, when disodium ethylenediaminetetraacetate is used as the chelating agent, the amount of chelating agent per 100 moles of salt (= (molar concentration of chelating agent / molar concentration of salt) × 100) can be 0.001 or more, 0.01 or more, 0.05 or more, 0.07 or more, 0.10 or more, 0.15 or more, 0.20 or more, 0.25 or more, or 0.30 or more, or can be 10 or less, 7.0 or less, 5.0 or less, 3.0 or less, 2.0 or less, 1.7 or less, or 1.5 or less.
[0056] For example, when sodium hexametaphosphate is used as the chelating agent, the amount of chelating agent per 100 moles of salt (= (molar concentration of chelating agent / molar concentration of salt) × 100) can be 0.1 or more, 0.5 or more, 1.0 or more, 1.2 or more, 1.5 or more, 1.7 or more, or 2.0 or more, and can be 20 or less, 15 or less, 10 or less, 7.0 or less, 5.0 or less, 4.5 or less, or 4.0 or less.
[0057] (aqueous medium) The second agent 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, or tap water can be used. The aqueous medium can be used alone or in combination of two or more types.
[0058] <Optional ingredients> The first and second agents of the cosmetic preparation of the present disclosure may contain various ingredients as appropriate, provided that the effects of the present invention are not affected. Examples of such ingredients include 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 ingredients may be used alone or in combination of two or more.
[0059] <<Method for preparing cosmetics>> The first and second agents of the cosmetic preparation of the present disclosure can be prepared, for example, using the following method. Note that the various materials that can be used in the preparation method of the first and second agents, such as hyaluronic acid, salts, chelating agents, water, buffer solutions, and optional ingredients, can be the same as those described above.
[0060] <Method for preparing the first agent> The first agent can be prepared by mixing a salt with water or a buffer solution to prepare a solution, adding hyaluronic acid to this solution, and dissolving the hyaluronic acid with stirring and mixing.
[0061] Alternatively, the first agent can be prepared by adding hyaluronic acid to water or a buffer solution, stirring and mixing to dissolve the hyaluronic acid, and then adding a salt.
[0062] In addition, when the buffer solution itself exhibits the above-mentioned salt concentration or ionic strength due to the action of a salt contained in the buffer solution, the addition of a salt can be omitted.
[0063] When the above-mentioned optional ingredients are to be added, they may be added before the hyaluronic acid is compacted with a salt, but it is preferable to add them after the compacted hyaluronic acid is prepared so as not to affect the compacted hyaluronic acid.
[0064] <Method for preparing the second agent> The second agent can be prepared by adding a chelating agent to water and mixing with stirring.
[0065] <Areas to apply cosmetics> The cosmetic composition of the present disclosure can be applied to any part of the body, for example, anywhere on the surface of the skin (body surface) or body hair (hair). Specifically, it can be applied appropriately to the skin surface of the face (lips, eyes, eyelids, cheeks, forehead, between the eyebrows, nose, etc.), head (scalp), ears, hands, arms, neck, legs, feet, chest, abdomen, back, etc., or to body hair such as hair, eyelashes, eyebrows, and beard. Here, skin also includes nails, which are formed by hardening due to changes in the keratin of the epidermis of the skin. Furthermore, body hair refers to hair that grows on the body. In the present disclosure, "body hair" can also be referred to as "hair."
[0066] As such, the cosmetic material of the present disclosure can be suitably used as a cosmetic material for skin or a cosmetic material for hair.
[0067] <Beauty method using cosmetics> A beauty method using the cosmetic composition of the present disclosure includes applying the first agent described above to a body surface or body hair, and then applying the second agent described above to the surface to which the first agent has been applied. Note that in this disclosure, the term "beauty method" refers to a method of applying the cosmetic composition of the present disclosure to a body surface or body hair to beautify and condition the body surface or hair, and is different from methods of surgery, treatment, or diagnosis for humans.
[0068] Generally, when skin or hair is exposed to dryness, moisture is lost without our realizing it, leading to a state in which the moisture content of the skin or hair surface cannot be maintained. For example, when the skin surface lacks moisture, the skin itself is unable to properly produce its own moisturizing components (natural moisturizing factors (NMFs)). As a result, the barrier function and moisturizing function of the skin surface are reduced, making the skin more susceptible to damage, which is thought to cause a loss of moisture and lead to wrinkles, rough skin, etc. Furthermore, for example, when hair loses moisture and becomes dry, split ends or breakage occurs, and static electricity can make hair more prone to frizz.
[0069] The cosmetic composition of the present disclosure allows the compacted hyaluronic acid to remain in the skin grooves or pores, or to be adsorbed on the surface of body hair, or, in some cases, to penetrate into the skin or body hair, and then captures and swells cations such as sodium ions that neutralize the negative charge of the carboxyl groups in the hyaluronic acid, thereby fully exhibiting the moisturizing properties of the hyaluronic acid itself and effectively moisturizing the skin or body hair. 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, or the moisture in hair is improved, thereby reducing the occurrence of problems such as rough skin, split ends, or broken hair, and thereby improving the cosmetic effect.
[0070] The means for applying the first and second agents to the body surface or hair is not particularly limited, and can be, for example, by spreading the first and second agents on the body surface or hair. The means for applying the first and second agents to the body surface or hair can be, for example, by spraying the first and second agents onto the skin or hair using a spray container containing the first and second agents, or by placing the first and second agents in a container without a spray function, collecting an appropriate amount of the first or second agent from the container on a finger or palm, and spreading it over the body surface or hair. [Example]
[0071] The present invention will be explained in more detail below with reference to test examples and examples, but the present invention is not limited to these.
[0072] Test Examples 1-4 <Evaluation of skin cosmetics> The test samples obtained by the manufacturing methods described below were used to carry out the various evaluations shown below, and the results are summarized in Tables 1 to 5 and FIGS.
[0073] (Evaluation of particle size ratio: swelling of hyaluronic acid) The average particle size of the hyaluronic acid particles in the test samples was evaluated based on the Z-average particle size measured by dynamic light scattering using a Zetasizer (Malvern Panalytical). The particle size ratio was calculated using the obtained average particle sizes and the following formula 4: Particle size ratio = average particle size of hyaluronic acid particles in a test sample containing a specified amount of chelating agent / average particle size of hyaluronic acid particles in a test sample containing no chelating agent ... Equation 4
[0074] (Evaluation of stratum corneum moisture content) After washing the inner part of the upper arm of the subject with soap (Savondor (trademark)), the subject was asked to spend 15 minutes in a temperature- and humidity-controlled room at a temperature of 25±1°C and a relative humidity of 50±5% to adjust the environment. Next, the moisture content of the skin surface of the washed inner part of the upper arm before application of the test sample and the amount of the test sample applied to the skin surface at a concentration of 2 μl / cm were measured. 2 The moisture content was measured 30 and 90 minutes after application of 18 μl at a rate of 10 μL using a Corneometer (trademark) CM825 (manufactured by Courage and Khazaka). When a second agent containing a chelating agent was used, the first agent was applied to the skin in the amount specified above, and then the second agent was applied to the same area in the same amount. The moisture content values in Table 4 represent the average of six measurements, and the "difference" is the value obtained by subtracting the actual value measured before application from each actual measurement.
[0075] (Evaluation of the number of pieces) After washing the inner part of the upper arm of the subject with soap (Savondor (trademark)), the subject was asked to spend 15 minutes in a temperature- and humidity-controlled room at a temperature of 25±1°C and a relative humidity of 50±5% to adjust the environment. Next, the number of grains on the skin surface of the washed inner part of the upper arm before the test sample was applied and the test sample was applied to the skin surface at a dose of 2 μl / cm 2 The number of creases was measured 30 and 90 minutes after application of 18 μl of the solution at a rate of 10 μl using a Handy Skin Sensor II (Shiseido Co., Ltd.). When a second agent containing a chelating agent was used, the first agent was applied to the skin in the amount specified above, and then the second agent was applied to the same area in the same amount. The crease count values in Table 5 are the average values of 6 measurements.
[0076] Test Example 1: Effect of chelating agents In Test Example 1, the effect of a chelating agent on compacted hyaluronic acid blended with a salt was examined. The results are shown in Tables 1 and 2 and Figures 1 and 2. Here, the amount of substance of the chelating agent (HMP) is the amount of substance converted to metaphosphoric acid (PO).
[0077] (Test sample preparation method) Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight-average molecular weight 1.2 million) was added to ion-exchange water to a concentration of 0.5% by mass and stirred and mixed with a vortex mixer to prepare Composition A. After dissolving the hyaluronic acid, magnesium chloride hexahydrate (MgCl2·6H2O) was added to each aliquot of Composition A at concentrations of 0.46%, 0.91%, and 1.42% by mass, or sodium chloride was added to each aliquot at concentrations of 0.82% and 1.23% by mass, and the mixture was stirred and mixed with a vortex mixer to prepare test samples that did not contain a chelating agent.
[0078] Next, sodium hexametaphosphate (HMP) was added as a chelating agent to each of the collected test samples that did not contain a chelating agent at the concentrations shown in Tables 1 and 2, and the mixture was stirred and mixed in a vortex mixer to prepare test samples that contained a chelating agent.
[0079] [Table 1]
[0080] [Table 2]
[0081] (result) As can be seen from the results of table 1-2 and figure 1-2, when chelating agent is mixed with the hyaluronic acid that is made compact by adding salt in a certain proportion, the particle size ratio of hyaluronic acid becomes large, that is, it can be confirmed that hyaluronic acid swells.This swelling of hyaluronic acid is considered to be due to chelating agent capturing the cation that electrostatically shields the negative charge of the carboxyl group of hyaluronic acid.
[0082] In this test, a sample bottle containing salt and hyaluronic acid to which a chelating agent was added was evaluated. However, it can be inferred that if an agent containing salt and hyaluronic acid is applied to the skin and then an agent containing a chelating agent is applied to the same area, the hyaluronic acid will swell in the same way.
[0083] Test Example 2: Types of chelating agents In Test Example 2, the swelling property of hyaluronic acid compacted by blending salt with a chelating agent other than sodium hexametaphosphate (HMP) was investigated. The results are shown in Table 3. Here, "control" in Table 3 refers to a test sample containing salt and hyaluronic acid without a chelating agent, and is the test sample used as a reference for comparing particle size ratios. In addition, "EDTA" in Table 3 refers to disodium ethylenediaminetetraacetic acid, "HIDA" refers to hydroxyethyliminodiacetic acid, and "DTPA" refers to diethylenetriaminepentaacetic acid.
[0084] (Test sample preparation method) Test samples were prepared using each chelating agent listed in Table 3 in the same manner as in Test Example 1. Magnesium chloride hexahydrate (MgCl2·6H2O) was used as the salt, with a salt concentration of 1.42 mass%. The concentration of the chelating agent was 0.03 mass% in each case.
[0085] [Table 3]
[0086] (result) As is clear from the results in Table 3, it was confirmed that hyaluronic acid swells even when a chelating agent other than sodium hexametaphosphate (HMP) is used.
[0087] Test Example 3: Evaluation of Moisture Retention (Stratum Cortex Moisture Content) In Test Example 3, the moisturizing properties of each test sample were evaluated based on the change in the moisture content of the stratum corneum over time. The results are shown in Table 4 and Figure 3.
[0088] Example 1 Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight-average molecular weight 1.2 million) was added to ion-exchanged water at a concentration of 0.5% by mass and stirred and mixed with a vortex mixer to prepare a composition. Magnesium chloride hexahydrate (MgCl2·6H2O) was added to this composition at a concentration of 1.42% by mass and stirred and mixed with a vortex mixer to prepare a test sample of the first agent.
[0089] Next, sodium hexametaphosphate (HMP) as a chelating agent was added to the ion-exchanged water at a concentration of 0.03% by mass, and the mixture was stirred and mixed with a vortex mixer to prepare a test sample of the second agent.
[0090] (Comparative Example 1) The first agent of Example 1 was used as the test sample of Comparative Example 1.
[0091] (Comparative Example 2) The second agent of Example 1 was used as the test sample of Comparative Example 2.
[0092] [Table 4]
[0093] (result) As can be seen from the results of Table 4 and Figure 3, when hyaluronic acid compacted by adding salt is applied to the skin, and then a chelating agent is applied, it is confirmed that the moisture content of the stratum corneum increases significantly.This is thought to be because the magnesium ions that neutralize the negative charge of the carboxyl group in hyaluronic acid are captured by the chelating agent, resulting in the moisturizing ability of hyaluronic acid itself being fully expressed, and the hyaluronic acid swells, increasing its water-retaining capacity.The results regarding the capture of cations by the chelating agent are consistent with the results of Tables 1-2 and Figures 1-2 mentioned above.
[0094] Test Example 4: Evaluation of moisturizing properties (skin texture count) In Test Example 4, moisturizing properties were evaluated based on the change over time in the number of skin textures caused by each test sample. The results are shown in Table 5 and Figure 4.
[0095] Example 2 The first and second agents of Example 1 were used as test samples of Example 2.
[0096] (Comparative Example 3) The first agent of Example 1 was used as the test sample of Comparative Example 3.
[0097] Comparative Example 4 The second agent of Example 1 was used as the test sample of Comparative Example 4.
[0098] [Table 5]
[0099] (result) As is clear from the results in Table 5 and Figure 4, it was confirmed that the number of skin textures increased when a chelating agent was applied after hyaluronic acid compacted with the addition of salt was applied to the skin. This is thought to be because, as shown in the results in Table 4 and Figure 3 above, the application of the first and second agents of Example 1 to the skin increased the moisture content of the stratum corneum, resulting in a plump and smooth skin texture.
[0100] <Reference Test Examples 1-6> For reference, the fact that hyaluronic acid can be compacted into particles by a salt and the effects of such hyaluronic acid particles will be explained below.
[0101] <Evaluation of Composition> The compositions obtained by the manufacturing methods described below were subjected to the various evaluations shown below, and the results are summarized in Tables 6 to 11 and Figures 5 to 10. In the tables and figures, "HA" stands for hyaluronic acid.
[0102] (Evaluation of average particle size) The average particle size of the hyaluronic acid particles in the composition was evaluated based on the Z-average particle size measured by dynamic light scattering using a Zetasizer (Malvern Panalytical) or a dynamic light scattering photometer DLS-8000 (Otsuka Electronics).
[0103] (Evaluation of moisture ratio) After washing the inner part of the upper arm of the subject with soap, the subject was asked to spend 20 minutes in a temperature- and humidity-controlled room at a temperature of 21±1°C and a relative humidity of 45±5% to adjust the environment. Next, the moisture content of the skin surface of the washed inner part of the upper arm before application of the composition was measured, and the composition was applied to the skin surface by applying one drop (2×2 cm) of the composition. 2 The moisture content was measured 20 minutes, 30 minutes, 60 minutes, and 120 minutes after application using a Corneometer (trademark) CM825 (manufactured by Courage and Khazaka). The moisture content ratio was calculated from the obtained moisture content using the following formula 5: Moisture content ratio = Moisture content after application of composition / Moisture content before application of composition ... Equation 5
[0104] Reference Test Example 1: Effect of ionic strength In Reference Test Example 1, the effect of ionic strength on the particle size of hyaluronic acid particles was investigated. The results are shown in Table 6 and FIG.
[0105] (Method of preparing the composition) Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) is added to ion-exchange water so that the content is 0.1% by mass, and is stirred and mixed with a vortex mixer to prepare composition B. After dissolving hyaluronic acid, sodium chloride is added to each of the collected composition B at concentrations of 0.01M (mol / L), 0.003M, 0.01M, 0.02M, 0.03M and 0.10M, so that the ionic strength of salt is 0.001, 0.003, 0.01, 0.02, 0.03 and 0.10, and is stirred and mixed with a vortex mixer to prepare hyaluronic acid particle-containing composition.Here, in the case of sodium chloride that is composed of monovalent cation and monovalent negative charge, the concentration of sodium chloride and the value of ionic strength are the same.
[0106] [Table 6]
[0107] (result) As can be seen from the results of Table 6 and Figure 5, it can be confirmed that by adding salt, hyaluronic acid particles of nanometer order can be obtained.In addition, with the increase in the amount of salt added, that is, with the increase in ionic strength, the particle size of hyaluronic acid particles tends to decrease, and it can be confirmed that, in particular, when ionic strength is 0.03 or more, hyaluronic acid particles of 100nm or less can be obtained.
[0108] Reference Test Example 2: Effects of hyaluronic acid concentration and ionic strength In Reference Test Example 2, the influence of the hyaluronic acid concentration and ionic strength during the preparation of the composition on the particle size of the hyaluronic acid particles was investigated. The results are shown in Table 7 and FIG.
[0109] (Method of preparing the composition) Each hyaluronic acid particle-containing composition was prepared in the same manner as in Reference Test Example 1, except that the hyaluronic acid concentration during composition preparation was 0.01 mass%, 0.1 mass%, 0.2 mass%, 0.3 mass%, 0.4 mass%, or 0.5 mass%, and sodium chloride was added so that the ionic strength was the ratio shown in Table 7.
[0110] [Table 7]
[0111] (result) As is clear from the results in Table 7 and Figure 6, it was confirmed that even if the concentration of hyaluronic acid increases, hyaluronic acid particles on the order of nanometers can be obtained by adding salt.
[0112] Reference Test Example 3: Effect of ionic strength when hyaluronic acid concentration is 0.4 to 0.5% by mass In Reference Test Example 3, the effect of ionic strength on hyaluronic acid particles was investigated when the concentration of hyaluronic acid during composition preparation was 0.4 to 0.5% by mass. The results are shown in Table 8 and FIG.
[0113] (Method of preparing the composition) Each hyaluronic acid particle-containing composition was prepared in the same manner as in Reference Test Example 1, except that the hyaluronic acid concentration was set to 0.4% by mass and 0.5% by mass, and sodium chloride was added so that the ionic strength was the ratio shown in Table 8.
[0114] [Table 8]
[0115] (result) As is clear from the results in Table 8 and Figure 7, it was confirmed that hyaluronic acid particles of 200 nm or less can be obtained when the ionic strength is 0.05 or more, regardless of whether the hyaluronic acid concentration is 0.4 mass% or 0.5 mass%. In particular, it was confirmed that when the hyaluronic acid concentration is 0.4 mass%, hyaluronic acid particles of 100 nm or less can be obtained when the ionic strength is in the range of 0.20 to 1.0.
[0116] Reference Test Example 4: Effect of particle size of hyaluronic acid particles on moisturizing properties In Reference Test Example 4, the effect of particle size of hyaluronic acid particles on moisturizing properties was investigated. The results are shown in Table 9 and Figure 8. Here, the moisture content ratio is greater than 1, the more improved the moisturizing performance is compared to the state before application of the composition. The moisture content ratio is preferably 1.25 or more, more preferably 1.30 or more, and particularly preferably 1.35 or more.
[0117] (Method of preparing the composition) Each hyaluronic acid particle-containing composition was prepared in the same manner as in Reference Test Example 1, except that the concentration of hyaluronic acid was set to 0.4% by mass, and sodium chloride was added so that the ionic strength was the ratio shown in Table 9. Here, the hyaluronic acid molecules in the composition with no sodium chloride added and ionic strength of 0 are thought to be spread out like threads and not take the form of particles, and therefore are indicated as "non-particle" in the tables and figures.
[0118] [Table 9]
[0119] (result) As can be seen from the results of table 9 and figure 8, in the case of the composition that contains non-particulate hyaluronic acid and the composition that contains the hyaluronic acid particles of average particle diameter more than 294nm, immediately after applying composition to skin, moisturizing performance temporarily increases, but this moisturizing performance decreases in only about 30 minutes, and only shows the moisturizing performance that is almost the same as the state that does not apply composition.This is thought to be because the hyaluronic acid in these compositions does not penetrate into the inside of skin.
[0120] On the other hand, when the composition contains hyaluronic acid particles with an average particle diameter of 84nm, it can be confirmed that when the composition is applied to the skin, it immediately exhibits excellent moisturizing performance, and this moisturizing performance can be maintained for a long time.The effect of this immediate effect and long-lasting moisturizing performance is thought to be due to the fact that the hyaluronic acid particles are ultrafine particles of 200nm or less, which can easily penetrate into the skin, and the content ratio of hyaluronic acid in the particles is high.
[0121] Reference Test Example 5: Effect of sodium citrate on the particle size of hyaluronic acid particles In Reference Test Example 5, the effect of sodium citrate on the particle size of hyaluronic acid particles was investigated. The results are shown in Table 10 and Figure 9.
[0122] (Method of preparing the composition) Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) is added to citrate buffer solution (Fujifilm Wako Pure Chemical Industries, Ltd.: pH 6.5, ionic strength 0.006) so that the content is 0.1% by mass, and then stirred and mixed with a vortex mixer to prepare composition C. After dissolving hyaluronic acid, sodium citrate is added to each of the collected compositions C so that the ionic strength of salt is 0.03, 0.06 and 0.30, and then stirred and mixed with a vortex mixer to prepare each hyaluronic acid particle-containing composition. Here, when the ionic strength is 0.03, the concentration of sodium citrate is 0.005M, when the ionic strength is 0.06, the concentration of sodium citrate is 0.010M, and when the ionic strength is 0.30, the concentration of sodium citrate is 0.050M.
[0123] [Table 10]
[0124] (result) As is clear from the results in Table 10 and FIG. 9, it was confirmed that hyaluronic acid particles of 200 nm or less can be obtained even when salts other than sodium chloride are used.
[0125] Reference Test Example 6: Effect of hyaluronic acid particle size on the use of additives that inhibit hydrogen bonding In Reference Test Example 6, we investigated the effect of the use of urea, an additive that inhibits hydrogen bonding, on the particle size of hyaluronic acid particles. The results are shown in Table 11 and Figure 10.
[0126] Reference Example 1 Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) is added to ion-exchange water so that the content is 0.1% by mass, and then stirred and mixed with a vortex mixer to prepare composition D. After dissolving hyaluronic acid, sodium chloride is added to composition D at a concentration of 0.10M so that the ionic strength of salt becomes 0.10, and then stirred and mixed with a vortex mixer to prepare a hyaluronic acid particle-containing composition.
[0127] Reference Example 2 Hyaluronic acid (Shiseido Co., Ltd., Biohyalo 12: weight average molecular weight 1.2 million) was added to an isotonic phosphate buffer solution (Takara Bio Inc.: pH 7.4, ionic strength 0.154) to a concentration of 0.1% by mass, and the mixture was stirred and mixed using a vortex mixer to prepare a composition containing hyaluronic acid particles.
[0128] (Reference Comparative Example 1) A composition of Reference Comparative Example 1 was prepared by blending 10 mass % of urea with respect to the total amount of the hyaluronic acid particle-containing composition of Reference Example 1.
[0129] (Reference Comparative Example 2) A composition of Reference Comparative Example 2 was prepared by blending 10% by mass of urea with respect to the total amount of the hyaluronic acid particle-containing composition of Reference Example 2.
[0130] [Table 11]
[0131] (result) From the results of table 11 and figure 10, it can be confirmed that when the urea that plays the role of breaking hydrogen bond is added into composition, the particle size of hyaluronic acid particle increases significantly.As is clear from this result, the particle size of the hyaluronic acid particle that uses salt to prepare varies depending on the blending of the urea that breaks hydrogen bond, so it can be considered that it is not the particle that can be obtained by cross-linking that is not affected by urea, but the particle that is granulated by hydrogen bond.
Claims
1. A first agent containing at least one salt selected from the group consisting of inorganic salts and organic acid salts, and hyaluronic acid; and a second agent for swelling the hyaluronic acid, the second agent comprising a chelating agent; The first agent and the second agent are individually configured. Cosmetics.
2. The cosmetic preparation according to claim 1, wherein the volume of hyaluronic acid in the first agent increases when the second agent is applied to the first agent.
3. The cosmetic preparation according to claim 1 or 2, wherein the hyaluronic acid is contained in an amount of 0.005% by mass or more relative to the total amount of the first agent.
4. The cosmetic preparation according to any one of claims 1 to 3, wherein the cation constituting the salt is a metal ion.
5. The chelating agent may be selected from the group consisting of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetic acid, trisodium ethylenediaminetetraacetic acid, nitrilotriacetic acid, sodium nitrilotriacetate, ammonium nitrilotriacetate, hydroxyethylethylenediaminetriacetic acid, sodium hydroxyethylethylenediaminetriacetate, pentetic acid, pentasodium pentetate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, imidisuccinic acid, tetrasodium imidisuccinate, ethylenediaminedisuccinic acid, trisodium ethylenediaminedisuccinate, hydroxyethyliminodiacetic acid, disodium hydroxyethyliminodiacetate, iminodisuccinic acid, tetrasodium iminodisuccinate, triethylenetetraminehexaacetic acid, sodium triethylenetetraminehexaacetate, methylglycinediacetic acid, trisodium methylglycinediacetate, hydroxyiminodisuccinic acid, tetrasodium hydroxyiminodisuccinate, L-aspartic acid The cosmetic preparation according to any one of claims 1 to 4, wherein the additive is at least one selected from the group consisting of tetrasodium L-aspartate diacetate, glutamic acid diacetate, tetrasodium glutamic acid diacetate, propanediaminetetraacetic acid, diammonium ethylenediaminetetraacetate, 1,3-diamino-2-hydroxypropane-tetraacetic acid, 1,3-diamino-2-hydroxypropane-tetraacetic acid, N,N-bis(2-hydroxyethyl)glycine, glycol ether diaminetetraacetic acid, dicarboxymethylglutamic acid, tetrasodium dicarboxymethylglutamate, hexametaphosphoric acid, diethylenetriaminepentaacetic acid, sodium hexametaphosphate, nitrilotris(methylenephosphonic acid), potassium nitrilotris(methylenephosphonate), 2-phosphonobutane-1,2,4-tricarboxylic acid, ethylenediaminetetramethylenephosphonic acid, pentasodium ethylenediaminetetramethylenephosphonate, phytic acid, and citric acid.
6. The cosmetic preparation according to any one of claims 1 to 5, wherein the weight-average molecular weight of the hyaluronic acid is 10,000,000 or less.
7. A beauty method using the cosmetic preparation according to any one of claims 1 to 6, After applying the first agent to a body surface or body hair, the second agent is applied to the surface to which the first agent has been applied. Beauty method.
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