JP2016199518A - Skin improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin improving agent which is excellent in moisturizing function, improves the oily and sticky feeling of a skin, when applied to the skin, and adjusts skin condition.SOLUTION: The skin improving agent contains a carboxymethyl group-containing modified hyaluronic acid and/or salt thereof as an active ingredient, wherein the hydrogen atoms of at least some hydroxyl groups at C-4 position and C-6 position of an N-acetylglucosamine constituting a hyaluronic acid and at C-2 position and C-3 position of a glucuronic acid constituting the hyaluronic acid are substituted by a group represented by -CH2-CO2H and/or -CH2-CO2-. The carboxymethyl group-containing hyaluronic acid and/or a salt thereof has a molecular weight of 400,000 or more, and the carboxymethylation rate to a disaccharide unit constituting a hyaluronic acid is 5 to 200%.SELECTED DRAWING: None

Description

  The present invention relates to a skin improving agent containing carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof as an active ingredient.

Hyaluronic acid is a mucopolysaccharide that is abundant in many tissues in the body (for example, subcutaneous tissue, eyeballs, joints), and is widely used as a component of cosmetics and the like due to its high moisturizing function. 1. Skin that can reduce or eliminate skin damage such as dryness, wrinkles, and stains of skin by adding sodium hyaluronate to a diameter of 10 to 150 nm and adding it to cosmetics at a high concentration exceeding 1% by weight. Improved cosmetics are described.
However, the moisturizing function and skin improvement effect of hyaluronic acid are not sufficient, and there is room for further improvement.

JP 2009-91298 A

  Therefore, the present invention provides a skin improving agent that has an excellent moisturizing function, improves the oily feeling of the skin when applied to the skin, and adjusts the skin tone.

  As a result of intensive studies to solve the above problems, the present inventor has excellent moisturizing function by containing carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof, and when applied to the skin, It has been found that it becomes a skin improving agent that improves the oily feeling and the feeling of stickiness and adjusts the skin tone, and has completed the present invention.

That is, the present invention
(1) Carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof as an active ingredient,
Skin improver,
(2) The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
A hydrogen atom of at least a part of the hydroxyl groups constituting hyaluronic acid is substituted with a group represented by —CH ₂ —CO ₂ H and / or —CH ₂ —CO ₂ ^— ,
(1) the skin improving agent described in the above,
(3) The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
The carboxymethylation rate for the disaccharide units constituting hyaluronic acid is 5% or more and 200% or less,
(1) or the skin improving agent according to (2),
(4) The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
The molecular weight is 250,000 or more,
(1) The skin improvement agent in any one of (3),
(5) containing 0.005 mass% or more and 5 mass% or less of the skin improving agent according to any one of (1) to (4),
Manufacturing method of cosmetics,
It is.

  ADVANTAGE OF THE INVENTION According to this invention, the skin improvement agent which is excellent in a moisturizing function, improves the oily feeling of a skin when it apply | coats to skin, and has a skin tone can be provided.

  Hereinafter, the present invention will be described in detail. In the present invention, “%” means “mass%” unless otherwise specified.

<Features of the present invention>
The skin-improving agent of the present invention contains a carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof, so that it has an excellent moisturizing function and improves the oily feeling and stickiness when applied to the skin. It is characterized by adjusting the skin tone.

<Carboxymethyl group-containing modified hyaluronic acid and / or salt thereof>
In the present invention, “modified hyaluronic acid and / or salt thereof” refers to hyaluronic acid and / or a salt thereof into which an organic group is introduced at least partially. In the present invention, the “organic group” refers to a group having a carbon atom.
Hyaluronic acid is a mucopolysaccharide widely distributed in living tissues such as chicken crown, umbilical cord, skin, cartilage, vitreous body and joint fluid. Since the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof of the present invention is made from hyaluronic acid as a raw material, it is considered that the biocompatibility is high and the skin irritation is low.

In the present invention, the term "carboxymethyl group" refers to the group represented by _{^"- -} CH ₂ -CO 2 H" or _"-CH 2 -CO _2".

  Therefore, in the present invention, “carboxymethyl group-containing modified hyaluronic acid and / or salt thereof” refers to hyaluronic acid and / or a salt thereof in which a carboxymethyl group is introduced into at least part of an organic group.

More specifically, in the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention, for example, a hydroxyl group (in the following formula (1)) constituting hyaluronic acid (see the following formula (1)), hyaluronic acid The hydrogen atoms of at least some of the hydroxyl groups at the C-4 position, the C-6 position of the N-acetylglucosamine that constitutes the C-2 position, and the C-3 position of the glucuronic acid that constitutes the hyaluronic acid are- A group represented by CH ₂ —CO ₂ H and / or —CH ₂ —CO ₂ ^— ). That is, in the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention, the hydrogen atom of the hydroxyl group at one or more of the hydroxyl groups at these positions is —CH ₂ —CO _2. The group represented by H and / or —CH ₂ —CO ₂ ^— may be substituted.

  In the present invention, the “disaccharide unit constituting hyaluronic acid” refers to one unit composed of disaccharides (glucuronic acid and N-acetylglucosamine) adjoining to constitute hyaluronic acid. “Carboxymethylation rate with respect to disaccharide units constituting the acid” is the number of carboxymethyl groups contained in the one unit. More specifically, when the unit is 100%, The ratio (%) of the number of carboxymethyl groups contained.

(In the formula, n represents an integer of 1 or more.)

  The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention can be, for example, a compound represented by the following formula (2).

(Wherein R ^{1 to} R ⁵ independently represent a hydrogen atom, a group represented by —CH ₂ —CO ₂ H, or a group represented by —CH ₂ —CO ₂ ^— , and n represents 1 or more. However, the case where R ^{1 to} R ^{5 of the} carboxymethyl group-containing modified hyaluronic acid and / or the entire salt thereof all represent a hydrogen atom is excluded.

<Molecular weight>
The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention has an excellent moisturizing function, improves skin oiliness and stickiness when applied to the skin, and improves skin tone. From the viewpoint of the agent, the molecular weight can be 250,000 or more.
Moreover, it can be 500,000 or more and 2 million or less, 800,000 or more and 2 million or less, 900,000 or more and 1.5 million or less, or 1 million or more and 1.5 million or less. In the present invention, the molecular weight of the carboxylmethyl group-containing modified hyaluronic acid and / or salt thereof can be measured by the following method.

Using a gel filtration column, a plurality of purified hyaluronic acids (reference substances) with known molecular weights are analyzed by liquid chromatography, and a calibration curve is created from their retention times.
Similarly, the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof to be measured is subjected to liquid chromatography analysis, and the molecular weight is determined using the calibration curve, whereby the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is obtained. The molecular weight of can be determined.

  Examples of the liquid chromatography analyzer that can be used for the liquid chromatography analysis include Waters Alliance 2690 HPLC Separations Module (manufactured by Waters), Waters Alliance 2695 HPLC Separations Module (manufactured by Waters), 1200 Series Manufactured). In addition, as a column that can be used for liquid chromatography analysis, for example, a column for ligand exchange chromatography (ligand exchange mode + size exclusion mode) manufactured by shodex, model name “SUGAR KS-801”, "SUGAR KS-802", "SUGAR KS-803", "SUGAR KS-804", "SUGAR KS-805", "SUGAR KS-806", "SUGAR KS-807", and a size exclusion chromatography column made by TOSOH Model name “TSKgel GMPW”.

<Carboxymethylation rate>
The carboxymethylation rate of the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention is determined by the methyl group of the N-acetyl group bonded to the C-2 position in the hyaluronic acid skeleton in the ¹ H-NMR spectrum ( A methylene group (—CH _{2 in} a group represented by —CH ₂ —CO ₂ H and / or —CH ₂ —CO ₂ ^— with respect to an integrated value of a peak (expressed in the vicinity of 2 ppm) indicating a proton of —CH ₃ ). It is represented by the ratio (%) of the integrated value of the peak (expressed in the range of 3.8 ppm or more and 4.2 ppm or less) indicating protons of-.

  In addition, the carboxymethyl group-containing modified hyaluron used in the present invention from the viewpoint of having a moisturizing function and improving the oily feeling of the skin when applied to the skin, as a skin improving agent for adjusting the condition of the skin. The acid and / or salt thereof may have a carboxymethylation rate (hereinafter also simply referred to as “carboxymethylation rate”) with respect to a disaccharide unit constituting hyaluronic acid of 5% or more and 200% or less, It can be 10% or more and 200% or less, or 50% or more and 200% or less. Further, it can be 60% or more, 70% or more, 80% or more, 150% or less, or 100% or less.

According to the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention, a repulsive force between molecules is generated due to the negative charge of the carboxymethyl group —CH ₂ —CO ₂ ^— , and the structure has a gap between the molecules. By taking in water,
It is considered to have a moisturizing function.
Moreover, when water is taken into the gaps between the structures of the molecules as described above, the carboxymethyl group-containing modified hyaluronic acid keeps moisture of the skin when the skin improving agent of the present invention is applied to the skin. It is presumed that the oiliness of the skin is improved by contacting the skin moisture with an appropriate ratio.
Furthermore, the negative charge of the carboxymethyl group —CH ₂ —CO ₂ ^— creates a repulsive force between molecules, giving the skin a softness when applied to the skin by giving flexibility to the three-dimensional structure of the molecules in the skin improving agent. It is presumed to improve the feeling.
It is considered that the skin tone is adjusted by applying the moisturizing function as described above and improving the feeling of oiliness and feeling when applied to the skin.

<Kinematic viscosity>
The kinematic viscosity of the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention may be 1 mm ² / s to 200 mm ² / s. The kinematic viscosity of the modified hyaluronic acid according to the present embodiment can be measured using an Ubbelohde viscometer (manufactured by Shibata Scientific Instruments Co., Ltd.). At this time, a Ubbelohde viscometer having a coefficient such that the number of seconds of flow is 200 seconds or more and 1,000 seconds is selected. The measurement is performed in a constant temperature water bath at 30 ° C. so that there is no temperature change. The kinematic viscosity (unit: mm ² / s) can be obtained from the product of the number of seconds of flow of the aqueous solution measured by the Ubbelohde viscometer and the coefficient of the Ubbelohde viscometer.

<Hue>
When the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention is used for the skin improving agent, the modified hyaluronic acid used in the present invention is colored because it does not affect the color of the white skin improving agent. It is preferable that the brightness of the glass is high and the yellowness is weak.

  The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention can have a b value (hereinafter also simply referred to as “b value”) representing a hue of a color of 5 or less, and 4 or less. Is preferably 3, or less, more preferably 0 or more.

  The b value is a value that defines the hue (hue) of the color of the substance. The larger the b value, the stronger the yellowness, while the smaller the b value, the stronger the blueness.

  In addition, the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention has an L value (hereinafter also simply referred to as “L value”) representing a color brightness of 90 or more (90 or more and 100 or less). The L value is preferably 92 or more, and the L value is more preferably 93 or more.

  The L value is a value that defines the lightness of the color of the substance, and is represented by a numerical value between 0 and 100. An L value of 100 indicates the brightest state (perfect white), while an L value of 0 indicates the darkest state (perfect black).

The b value and the L value can be displayed in Lab chromaticity coordinates by a color difference display method defined by JIS Z 8730.
Moreover, b value and L value can be measured with a commercially available color difference meter.
In the present invention, the b value and the L value are measured for solid carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof.

  The b-value and L-value of the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention can be determined by, for example, a color difference meter (trade name “COLOR AND COLOR DIFFERENCE METERMODEL 1001 DP”, manufactured by Nippon Denshoku Industries Co., Ltd.). A 10Φ lens is attached, and measurement can be performed by laying 1 g or more of a measurement sample on a glass cell.

  According to the modified carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention, the b value measured by a color difference meter is 5 or less (moreover, the L value is 90 or more). It can be used as a raw material for a skin improving agent without necessity.

<Method for producing carboxymethyl group-containing modified hyaluronic acid and / or salt thereof>
The method for producing a carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention comprises a raw material hyaluronic acid dissolved in a hydrous solvent having a temperature of 30 ° C. or lower, more preferably 10 ° C. or lower, and 0 ° C. or higher and 10 ° C. or lower. And / or reacting the salt with haloacetic acid and / or a salt thereof.
Here, the water-containing solvent is water or a mixed solution of a water-soluble organic solvent and water, and in the case of the mixed solution, the water-containing solvent can contain 60 v / v% or less of the water-soluble organic solvent. Examples of the water-soluble organic solvent include alcohol solvents such as methanol, ethanol, 1-propanol, and 2-propanol, ketone solvents such as acetone and methyl ethyl ketone, tetrahydrofuran, acetonitrile, and the like. Can be used in combination. The haloacetic acid can also be chloroacetic acid and / or its salt, or bromoacetic acid or its salt. The reaction can be carried out under basic conditions, for example, the pH of the reaction solution (hydrous solvent) is 9 or more and 9 or more and 14 or less.

The method for producing a carboxymethyl group-containing modified hyaluronic acid and / or salt thereof used in the present invention is carried out at a low reaction temperature of 30 ° C. or less in the step of reacting with the haloacetic acid and / or salt thereof. More than 400,000 carboxymethyl group-containing modified hyaluronic acid and / or salt thereof can be easily obtained.
In addition, a carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof having a lightness of b value of 5 or less and L value of 90 or more and low yellowness can be easily obtained.

<Skin improver>
Since the skin improving agent according to this embodiment contains the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof as an active ingredient, the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is used as it is. However, it is preferable to add a solvent such as fresh water, an excipient such as dextrin, or other raw materials for skin cosmetics.
Further, the carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof may be used as a skin oiliness improving agent or a skin feeling improvement agent.

<Uses of skin improvers>
The skin improving agent according to this embodiment can be used for various skin cosmetics.
Examples of skin cosmetics include facial cleansers, cleansers, lotions (eg, whitening lotions), creams (eg, vanishing cream, cold cream), emulsions, gels, cosmetics, packs (eg, jelly). Peel-off type, paste-type wipe-off type, powder-type wash-out type), face mask, cleansing, foundation, lipstick, lip balm, lip gloss, lip liner, blusher, makeup base, shaving lotion, sunscreen, after sun lotion, deodorant lotion , Body lotions (including hand care lotions and foot care lotions), body oils, soaps and bath additives.

<Content of skin improver in skin cosmetics>
The content of the skin improving agent in the skin cosmetic is excellent in moisture retention function, and when applied to the skin, improves the oily feeling of the skin and the feeling of stickiness, and from the viewpoint of making the skin improving agent to condition the skin, Carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof may be contained in an amount of 0.005% to 5% as a skin improving agent. Furthermore, it can be 0.01% or more, 2% or less, and 1% or less. By setting the content within the above range, it is possible to exhibit the effect of improving the feeling of oiliness and the feeling of the skin, and the moisturizing function is not changed. If the content is larger than the above range, the viscosity of the skin cosmetic itself becomes too high, and it may be difficult to extend the entire skin.

<Other hyaluronic acids>
The skin improving agent of the present invention can contain other hyaluronic acids in addition to carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof. Here, other hyaluronic acids are hyaluronic acid and / or a salt thereof (sodium hyaluronate, zinc hyaluronate, hydrolyzed hyaluronic acid, etc.), cationized hyaluronic acid, acetylated hyaluronic acid, dimethylsilanol hyaluronic acid, hydrolysis Examples include alkyl hyaluronate (C12-13) glyceryl.

[Example 1] <Preparation of skin improver>
After weighing 1.04 g of sodium hydroxide into a 30 mL sample bottle, 8 mL of water was added and dissolved. Next, 2.0 g of hyaluronic acid was added and dissolved, then 1.52 g of sodium monobromoacetate was added and dissolved, and the mixture was allowed to stand at 10 ° C. for 16 hours. Here, the pH of the reaction solution was 13. Thereafter, 80 mL of ethanol was placed in a 200 mL beaker, and the reaction solution was added with stirring to precipitate carboxymethyl group-containing modified hyaluronic acid. Thereafter, the precipitate was collected in a 200 mL beaker with a 400-mesh filter cloth, and then 40 mL of a 10% sodium chloride aqueous solution was added to dissolve the precipitate. Further, after adjusting the pH with an 8% aqueous hydrochloric acid solution, 80 mL of ethanol was added to the solution while stirring to precipitate the carboxymethyl group-containing modified hyaluronic acid again. After washing with 100 mL of 80% water-containing ethanol three times, filtration under reduced pressure, and drying under reduced pressure at 55 ° C. for 3 hours, a carboxymethyl group-containing modified hyaluronic acid having a molecular weight of 1 million carboxymethylation rate of 80% was obtained. The skin improver (carboxymethyl group-containing modified hyaluronic acid) of Example 1 was used.
The carboxymethyl group-containing modified hyaluronic acid color difference meter of Example 1 (trade name “COLOR AND COLOR DIFFERENCE METERMODEL 1001 DP”, manufactured by Nippon Denshoku Industries Co., Ltd.) has a b value of 5 or less and an L value of 90 or more. there were. The kinematic viscosity was in the range below ^{1 mm} 2 / s or more 200 mm ² / s.

[Example 2] <Preparation of skin improver>
The carboxymethyl group-containing modified hyaluronic acid of Example 2 was prepared in the same manner as in Example 1 except that the reaction temperature and time with sodium monobromoacetate in Example 1 were changed to 60 ° C. for 3 hours.
As a result, a carboxymethyl group-containing modified hyaluronic acid having a molecular weight of 100,000, a carboxymethylation rate of 60%, a b value of 8.9, an L value of 91, and a kinematic viscosity in the range of 1 mm ² / s to 200 mm ² / s is obtained. This was used as the skin improving agent of Example 2.
The skin improving agent (carboxymethyl group-containing modified hyaluronic acid) of Example 2 was slightly browned visually as compared with Example 1.

The carboxylation rate of the carboxymethyl group-containing modified hyaluronic acid was determined from the integrated value of ¹ H-NMR spectrum by the following method.

(Sample preparation)
7 mg of sample and 1 mg of sodium 4,4-dimethyl-4-silapentanesulfonate (DSS) as an internal standard substance were dissolved in 0.7 mL of heavy water, transferred to an NMR sample tube, and capped.

(Measurement condition)
Apparatus: Varian NMR system 400NB type (Varian Technologies Japan Limited)
Observation frequency: 400 MHz
Temperature: 30 ° C
Standard: DSS (0 ppm)
Integration count: 64 times

(analysis method)
The peak of the N-acetyl group (CH ₃ ) of hyaluronic acid appearing in the vicinity of 2.0 ppm of the ¹ H-NMR spectrum and the methylene group (—CH ₂ —) of the carboxymethyl group appearing in the range of 3.8 ppm to 4.2 ppm. ) Peak was integrated. From the integrated value, the number of carboxymethyl groups bonded to each disaccharide repeating unit of hyaluronic acid constituting the modified hyaluronic acid was determined from the following formula to determine the carboxymethylation rate (CM conversion rate).
CM conversion rate = (peak integrated value / 2 appearing in the range of 3.8 ppm to 4.2 ppm) / (2.0 ppm peak integrated value / 3)

  The molecular weight of carboxymethyl group-containing modified hyaluronic acid is determined by liquid chromatography analysis of multiple purified hyaluronic acids (reference substances) with known molecular weights using a gel filtration column, and a calibration curve is created from their retention times. To do. Similarly, the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof to be measured is subjected to liquid chromatography analysis, and the molecular weight is determined using the calibration curve, whereby the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof The molecular weight of was determined.

[Formulation Example 1] <Preparation of cosmetics>
A lotion of Formulation 1 was prepared. Specifically, the raw materials shown in the following formulation 1 containing the carboxymethyl group-containing modified hyaluronic acid obtained in Example 1 were mixed little by little, and the carboxymethyl group-containing modified hyaluronic acid and / or salt thereof was 1%. The containing cosmetic was obtained.

<Formulation 1> Cosmetics Skin improvement agent of Example 1 (carboxymethyl group-containing modified hyaluronic acid) 1%
Ethanol 4.5%
Glycerin 3%
Polyethylene glycol 1500 2%
1,3-butylene glycol 2%
Phenoxyethanol 0.2%
Methylparaben 0.1%
EDTA-2Na 0.1%
Sodium citrate 0.09%
Citric acid 0.01%
Ion exchange water

[Comparative Example 1] <Preparation of cosmetics>
A cosmetic material of Comparative Example 1 was obtained in the same manner as in the cosmetic material of Formulation Example 1 except that the equivalent amount of the carboxymethyl group-containing modified hyaluronic acid of Example 1 was replaced with sodium hyaluronate having a molecular weight of 1,000,000.

[Test Example 1]
About the cosmetics of the formulation example 1 and the comparative example 1, the skin tone at the time of apply | coating to skin according to the following evaluation methods and evaluation criteria was evaluated. The results are shown in Table 1.

<Evaluation method>
The cosmetics of Formulation Example 1 and Comparative Example 1 were applied to the faces of 10 panelists every day for 5 days, and the skin condition was evaluated for the skin condition on the 5th day from the start of application. Based on the following evaluation criteria, the evaluation results were scored and the average score was calculated.

<Evaluation criteria for usability>
1 point: Skin tone is very bad 2 points: Skin tone is slightly bad 3 points: Equivalent to Comparative Example 1 4 points: Skin tone is good 5 points: Skin tone is very good

From the results of Table 1, the cosmetic of Formulation Example 1 containing the skin improver of Example 1 (carboxymethyl group-containing modified hyaluronic acid) has an average score of 3.4 on the fifth day after application, Compared to Example 1, the skin tone improved.
On the other hand, it was shown that the cosmetic of Comparative Example 1 containing sodium hyaluronate was less likely to improve skin tone as compared to Formulation Example 1.

[Test Example 2]
About the cosmetics of the formulation example 1 and the comparative example 1, the oiliness of the skin at the time of apply | coating to skin according to the following evaluation methods and evaluation criteria was evaluated. The results are shown in Table 2.

<Evaluation method>
The cosmetics of Formulation Example 1 and Comparative Example 1 were applied to the faces of 10 panelists every day for 5 days, and the skin was evaluated for the oiliness of the skin on the 5th day from the start of application. Based on the following evaluation criteria, the evaluation results were scored and the average score was calculated.

<Evaluation criteria for usability>
1 point: The skin is oily 2 points: The skin is slightly oily 3 points: Equivalent to Comparative Example 1 4 points: The oily skin is slightly improved 5 points: Skin The oiliness has improved

From the results of Table 2, the cosmetic of Formulation Example 1 containing the skin improver (carboxymethyl group-containing modified hyaluronic acid) of Example 1 has an average score of 3.5 on the fifth day after application, Compared with Example 1, the oiliness of the skin was improved.
On the other hand, it was shown that the cosmetic of Comparative Example 1 containing sodium hyaluronate was less likely to improve skin oiliness compared to Formulation Example 1.

[Test Example 3]
About the cosmetics of the formulation example 1 and the comparative example 1, evaluation of the feeling of the skin when applying to skin according to the following evaluation methods and evaluation criteria was performed. The results are shown in Table 3.

<Evaluation method>
The cosmetics of Formulation Example 1 and Comparative Example 1 were applied to the faces of 10 panelists every day for 5 days, and the skin was evaluated for the feeling of stickiness on the 5th day after application. Based on the following evaluation criteria, the evaluation results were scored and the average score was calculated.

<Evaluation criteria for usability>
1 point: The feeling of stickiness of the skin has decreased 2 points: The feeling of stickiness of the skin has decreased slightly 3 points: Same as Comparative Example 4 4: The feeling of feeling of skin has improved slightly 5 points: Skin The feeling of feeling has improved

From the results of Table 3, the cosmetic of Formulation Example 1 containing the skin improver of Example 1 (carboxymethyl group-containing modified hyaluronic acid) has an average score of 3.4 on the fifth day after application, Compared to Example 1, the feeling of skin was improved.
On the other hand, it was shown that the cosmetic of Comparative Example 1 in which sodium hyaluronate was blended was less likely to improve the skin-feeling feeling compared to Formulation Example 1.

[Examples 3 to 7] <Preparation of skin improver>
Various carboxymethyl group-containing modified hyaluronic acids and / or salts thereof were prepared according to Example 1 except that carboxymethyl group-containing modified hyaluronic acid having a different molecular weight and carboxymethylation rate was used, and the skins of Examples 3 to 7 An improver was used.
The carboxymethyl group-containing modified hyaluronic acid having different molecular weight and carboxymethylation rate used in Examples 3 to 7 was obtained by changing the sodium monobromoacetate of Example 1, the standing temperature and time of the reaction.
The carboxymethyl group-containing modified hyaluronic acid used in Example 3 was reacted with sodium monobromoacetate at 4 ° C. for 48 hours.
The carboxymethyl group-containing modified hyaluronic acid used in Example 4 was reacted at 25 ° C. for 3 hours using sodium monobromoacetate.
The carboxymethyl group-containing modified hyaluronic acid used in Example 5 was reacted with monobromoacetic acid at 4 ° C. for 24 hours.
The carboxymethyl group-containing modified hyaluronic acid used in Example 6 was reacted at 4 ° C. for 3 hours using sodium monobromoacetate.
The carboxymethyl group-containing modified hyaluronic acid used in Example 7 was reacted at 25 ° C. for 48 hours using monochloroacetic acid.
The b value and L value of the carboxymethyl group-containing modified hyaluronic acid used in Examples 3 to 7 were all b values of 5 or less and L values of 90 or more. The kinematic viscosity was in the range of 1 mm ² / s to 200 mm ² / s.

[Test Example 2: Water retention test]
The weighing bottle was placed in a vacuum dryer together with 10 g of phosphorus (V) oxide and dried at 60 ° C. for 30 minutes under reduced pressure. After the dried weighing bottle was cooled in a desiccator, the weight of the empty weighing bottle was measured, and a 1.0% solution of the skin improving agent (carboxymethyl group-containing modified hyaluronic acid) of Examples 3 to 7 was used. 0 g was weighed. In addition, hyaluronic acid (manufactured by QP Corporation) having the same molecular weight (1.2 million) as the carboxymethyl group-containing modified hyaluronic acid obtained in Example 3 was weighed in a weighing bottle in the same manner, and Comparative Example 2 and did. Next, these weighing bottles were put in a desiccator in which silica gel was enclosed, put in a thermostat at 35 ° C. and held for 19.5 hours, and then mass was measured. The water retention rate (%) was calculated based on the following formula.
Water retention rate (%) = {(mass of sample before putting in thermostat) − (mass of sample after 19.5 hours)} / (mass of sample before putting in thermostat) × 100 (%)

  Table 4 shows the measurement results of the water retention of the carboxymethyl group-containing modified hyaluronic acid and the hyaluronic acid.

From the results of Table 4, it can be understood that the skin improvement agent (carboxymethyl group-containing modified hyaluronic acid) of the present invention has a higher water retention rate than hyaluronic acid having the same molecular weight.
From the results shown in Table 4, the skin improvers of Examples 3 to 7 containing carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof having a molecular weight of 250,000 or more or a carboxymethylation rate of 5% to 200%. It can be understood that the water retention rate is higher than that of the hyaluronic acid of Comparative Example 2.

Claims (5)

Carboxymethyl group-containing modified hyaluronic acid and / or a salt thereof as an active ingredient,
Skin improver. The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
A hydrogen atom of at least a part of the hydroxyl groups constituting hyaluronic acid is substituted with a group represented by —CH ₂ —CO ₂ H and / or —CH ₂ —CO ₂ ^— ,
The skin improving agent according to claim 1. The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
The carboxymethylation rate for the disaccharide units constituting hyaluronic acid is 5% or more and 200% or less,
The skin improving agent according to claim 1 or 2. The carboxymethyl group-containing modified hyaluronic acid and / or salt thereof is
The molecular weight is 250,000 or more,
The skin improving agent according to any one of claims 1 to 3. Containing 0.005% by mass or more and 5% by mass or less of the skin improving agent according to claim 1;
A method for producing cosmetics.