JP2013181001A - Hyaluronic acid composition and skin care preparation including the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide: a hyaluronic acid composition that has high moisturizing effect for skin and can raise a water content of the skin; and a skin care preparation including the same.SOLUTION: A hyaluronic acid composition is an acid composition that includes: a low-molecular weight hyaluronic acid having at most 100,000 of an average molecular weight and/or a salt thereof; and a cationization hyaluronic acid and/or a salt thereof so that the content ratio becomes 5:95-80:20 by a mass ratio, wherein an aqueous solution of the hyaluronic acid composition that is prepared so that the low molecular weight hyaluronic acid and/or the salt and the cationization hyaluronic acid and/or the salt become 1 mass% in total by a hyaluronic acid conversion dissolves in water without causing a precipitate.

Description

  The present invention relates to a hyaluronic acid composition containing low-molecular hyaluronic acid and cationized hyaluronic acid, a skin external preparation using the composition, and a method for increasing the amount of skin moisture using the hyaluronic acid composition.

  Hyaluronic acid is a mucopolysaccharide widely distributed in living tissues such as chicken crown, umbilical cord, skin, cartilage, vitreous body and joint fluid, and is widely used as a component of cosmetics due to its high moisturizing function.

  However, hyaluronic acid, which is generally used as an external preparation for skin, is a high-molecular polysaccharide and is therefore difficult to be absorbed in the living body. For example, by applying hyaluronic acid to the skin, it is possible to prevent moisture from evaporating from the skin. However, since hyaluronic acid is a polymer (average molecular weight: 500,000 to 2,000,000), it hardly penetrates into skin tissue. Most of it only stays on the surface of the skin. Therefore, if hyaluronic acid on the skin surface is washed away by face washing or bathing, the skin moisturizing effect is difficult to sustain.

  Therefore, a composition containing hyaluronic acid and hyaluronic acid oligosaccharide having a weight average molecular weight of 700,000 to 1.5 million is described as hyaluronic acid that easily penetrates into the skin (Patent Document 1).

JP 2011-57607 A

  However, in the case of the composition described in Patent Document 1, it was developed to increase the permeability from the keratin gap in the epidermis, but it was difficult to say that the skin moisturizing effect was sufficient.

  An object of the present invention is to provide a hyaluronic acid composition having a high moisturizing effect on the skin, a skin external preparation containing the composition, and a method for increasing the amount of skin moisture using the composition.

The present invention
(1) Hyaluronic acid composition in which the content ratio of low molecular weight hyaluronic acid and / or salt thereof and cationized hyaluronic acid and / or salt thereof having an average molecular weight of 100,000 or less is 5:95 to 80:20 by mass ratio Because
An aqueous solution of the hyaluronic acid composition prepared by adding the low molecular weight hyaluronic acid and / or salt thereof and the cationized hyaluronic acid and / or salt thereof to a total amount of 1% by mass in terms of hyaluronic acid produces a precipitate. Hyaluronic acid composition, characterized in that it is dissolved in water,
(2) The hyaluronic acid composition according to (1), wherein the low molecular weight hyaluronic acid and / or salt thereof has an average molecular weight of 400 to 50,000,
(3) The composition according to (1) or (2), further comprising hyaluronic acid having an average molecular weight of more than 100,000 and / or a salt thereof,
(4) a skin external preparation containing the hyaluronic acid composition according to any one of (1) to (3),
(5) A method for increasing the amount of skin moisture using the hyaluronic acid composition according to any one of (1) to (3),
It is.

When the hyaluronic acid composition is applied to the skin, the moisture content of the skin can be increased, so that the skin can be kept fresh.
Moreover, the said hyaluronic acid composition can further enhance the moisturizing effect of a normal hyaluronic acid having an average molecular weight of over 100,000. Therefore, it is possible to enhance the moisturizing effect without increasing the blending amount of the moisturizing agent by adding the hyaluronic acid composition to the skin external preparation containing the hyaluronic acid having an average molecular weight exceeding 100,000 as the moisturizing agent. It is.

  Hereinafter, a hyaluronic acid composition containing a low molecular weight hyaluronic acid and / or salt thereof and a cationized hyaluronic acid and / or salt thereof according to an embodiment of the present invention, and a skin external preparation containing the same will be described in detail. In the present invention, “%” means “mass%” and “part” means mass part.

1. Hyaluronic acid composition 1.1. Low molecular weight hyaluronic acid and / or salt thereof The hyaluronic acid composition according to the present embodiment includes low molecular weight hyaluronic acid and / or a salt thereof having an average molecular weight of 100,000 or less.
The average molecular weight of the low molecular weight hyaluronic acid and / or salt thereof is preferably 400 to 50,000, more preferably 1,000 to 30,000, from the viewpoint of excellent effect of increasing skin moisture. More preferred.

1.1.1. Average molecular weight In the present invention, the average molecular weight of hyaluronic acid and / or a salt thereof is a value measured by the following method.

That is, about 0.05 g of hyaluronic acid and / or a salt thereof (this product) was precisely weighed and dissolved in a 0.2 mol / L sodium chloride solution to make exactly 100 mL, and this solution 8 mL, 12 mL and 16 mL Is accurately measured, and a 0.2 mol / L sodium chloride solution is added to each to make exactly 20 mL. This sample solution and a 0.2 mol / L sodium chloride solution were measured at 30.0 ± 0.1 ° C. according to the Japanese Pharmacopoeia (Fifteenth revision) general test method viscosity measurement method (first method capillary viscometer method). The specific viscosity is measured by (Equation (A)), and the reduced viscosity at each concentration is calculated (Equation (B)). A graph is drawn with the reduced viscosity on the vertical axis and the concentration (g / 100 mL) of the product converted to dry matter on the horizontal axis, and the intrinsic viscosity is determined from the intersection of the straight line connecting the points and the vertical axis. Substituting the intrinsic viscosity obtained here into Laurent's formula (formula (C)) to calculate the average molecular weight (TC Laurent, M. Ryan, A. Pietruszkiewicz,: BBA, 42, 476-485 (1960)) .

(Formula A)
Specific viscosity = {required flow time of sample solution) / (required flow time of 0.2 mol / L sodium chloride solution)} − 1

(Formula B)
Reduced viscosity (dL / g) =
Specific viscosity / (Concentration g / 100mL with respect to the dried product converted to this product))

(Formula C)
Intrinsic viscosity (dL / g) = 3.6 × 10 ⁻⁴ M ^0.78
M: average molecular weight

1.1.2. Method for producing low molecular hyaluronic acid and / or salt thereof The raw material hyaluronic acid and / or salt thereof used in the production of the low molecular hyaluronic acid and / or salt thereof is a living tissue such as an animal (for example, chicken crown, umbilical cord, It may be extracted from skin, synovial fluid, etc., or obtained by culturing microorganisms, animal cells or plant cells (eg fermentation using bacteria of the genus Streptococcus), chemical or enzymatic Those synthesized in the above can be used.

  The method for producing the low-molecular hyaluronic acid and / or salt thereof is not particularly limited, and can be carried out using a known hydrolysis method from the raw material hyaluronic acid. For example, a method of reducing the molecular weight of hyaluronic acid using an enzyme or the like, a method of reducing the molecular weight under acid or alkaline conditions, and the like can be mentioned. Among them, hyaluronic acid and / or a salt thereof is contained in an acidic water-containing medium because it is easy to separate and purify the obtained low-molecular hyaluronic acid and / or a salt thereof, and can be produced at a low cost with a high yield. It is preferable to manufacture by dispersing.

  The low molecular weight hyaluronic acid and / or salt thereof is preferably a purified product, specifically, hyaluronic acid and / or salt thereof having a purity of 90% or more. When low molecular hyaluronic acid and / or a salt thereof having a purity of less than 90% is used, the moisturizing effect of the hyaluronic acid composition containing low molecular hyaluronic acid and / or a salt thereof and cationized hyaluronic acid and / or a salt thereof is improved. Since it may decrease, it is not preferable.

1.2. Cationized hyaluronic acid and / or salt thereof The hyaluronic acid composition according to this embodiment includes cationized hyaluronic acid and / or a salt thereof.

1.2.1. Method for producing cationized hyaluronic acid and / or salt thereof The raw material hyaluronic acid and / or salt thereof used for producing the cationized hyaluronic acid and / or salt thereof has an average molecular weight, a moisturizing feeling after use, and skin In terms of ease of blending into an external preparation, it is more preferably from 800 to 2,500,000, and even more preferably from 50,000 to 2,000,000.

  The cationized hyaluronic acid and / or salt thereof used in the external preparation for skin of the present invention can be obtained by reacting the raw material hyaluronic acid and / or salt thereof with a cationizing agent in a basic water-containing medium. According to the said method, the efficiency of a manufacturing process can be improved compared with the case where the raw material hyaluronic acid and / or its salt are dissolved in water, and made to react with a cationizing agent, for example.

  In the method for producing cationized hyaluronic acid and / or salt thereof, in the step of reacting raw material hyaluronic acid and / or salt thereof with a cationizing agent in a basic water-containing medium, the raw material hyaluronic acid and / or salt thereof is a base. It is preferable to make it react with a cationizing agent in the state disperse | distributed in the property water-containing medium. Here, the degree of cationization can be adjusted by adjusting the reaction conditions (time, temperature, etc.).

  As a usable cationizing agent, a cationizing agent containing a quaternary ammonium-containing group is preferable. Examples thereof include cationizing agents containing a quaternary ammonium group such as 2,3-epoxypropyltrialkylammonium halide (glycidyltrialkylammonium salt) and 3-halogeno-2-hydroxypropyltrialkylammonium halide. Such cationizing agents may be used alone or in combination of two or more. Among these, the cationizing agent is preferably 3-chloro-2-hydroxypropyltrimethylammonium chloride and / or glycidyltrimethylammonium chloride.

1.3. Content ratio of low molecular hyaluronic acid and / or salt thereof and cationized hyaluronic acid and / or salt thereof The hyaluronic acid composition according to the present embodiment comprises low molecular hyaluronic acid and / or salt thereof and cationized hyaluronic acid and / or The content ratio of the salt is 5:95 to 80:20, preferably 10:90 to 75:25, and more preferably 20:80 to 40:60 by mass ratio.
The hyaluronic acid composition according to the present embodiment increases the moisture content in the skin when the content ratio of the low-molecular hyaluronic acid and / or salt thereof and the cationized hyaluronic acid and / or salt thereof is the above-described mass ratio. Can do.

The method for producing a hyaluronic acid composition according to the present embodiment is particularly limited as long as it is a method capable of obtaining a composition containing hyaluronic acid and / or a salt thereof and cationized hyaluronic acid and / or a salt thereof. is not. For example, a solution containing hyaluronic acid and / or a salt thereof and a solution containing cationized hyaluronic acid and / or a salt thereof are mixed, dried by spray drying, freeze drying, etc. Pulverization, powder containing hyaluronic acid and / or salt thereof and powder containing cationized hyaluronic acid and / or salt thereof are mixed to obtain a powdery composition. Can be mentioned.
The hyaluronic acid composition according to the present embodiment can be obtained by mixing a solution containing hyaluronic acid and / or a salt thereof and a solution containing cationized hyaluronic acid and / or a salt thereof, In the mixed solution, the hyaluronic acid composition is dissolved in water without causing precipitation, and can be suitably used for an external preparation for skin.

2. Skin external preparation The skin external preparation according to this embodiment contains the hyaluronic acid composition. For example, the external preparation for skin according to the present embodiment can contain the hyaluronic acid composition as a moisturizing agent. Moreover, the skin external preparation which concerns on this embodiment contains the said hyaluronic acid composition normally 0.001-5% in conversion of solid content. If the content is less than 0.001%, a satisfactory moisturizing effect cannot be obtained, so that there is a possibility that the drying of the skin during use cannot be improved. If the content exceeds 5%, the viscosity becomes too high and it may be difficult to extend the whole skin.

  Although the aspect of the skin external preparation which concerns on this embodiment is not specifically limited, For example, skin cosmetics are mentioned. By using the hyaluronic acid composition in a cosmetic for skin, the effect of increasing the amount of moisture in the skin is high, so that the skin can be moisturized for a long period of time, and the feeling of bulkiness of the skin can be improved. Examples of the cosmetic for skin according to the present embodiment include, for example, face wash, cleanser, lotion (for example, whitening lotion), cream (for example, vanishing cream, cold cream), milky lotion, cosmetic liquid, pack ( For example, jelly-type peel-off type, paste-type wipe-off type, powder-type wash-out type), cleansing, foundation, lipstick, lip balm, lip gloss, lip liner, blusher, shaving lotion, after sun lotion, deodorant lotion, body lotion (hand care lotion) Body oils, soaps, and bath additives.

  According to the external preparation for skin according to this embodiment, since the moisture content of the skin can be increased by containing the hyaluronic acid composition, the skin can be moisturized.

  The external preparation for skin according to this embodiment preferably contains hyaluronic acid having an average molecular weight of more than 100,000 and / or a salt thereof. Hyaluronic acid having an average molecular weight of more than 100,000 has a moisturizing function but does not have a sufficient moisturizing effect. By adding the hyaluronic acid composition according to the present invention to a composition containing hyaluronic acid having an average molecular weight of more than 100,000, the moisturizing function of the hyaluronic acid can be enhanced and the moisturizing effect can be maintained. Specifically, 0.1% of the mixture of the hyaluronic acid and the hyaluronic acid composition according to the present invention is compared with the amount of skin moisture when the 0.1% aqueous solution of hyaluronic acid is applied to the skin. When the aqueous solution is applied to the skin, the amount of moisture in the skin increases. The blending ratio of hyaluronic acid having an average molecular weight of over 100,000 and the total content of low molecular weight hyaluronic acid and / or salt thereof and cationized hyaluronic acid and / or salt thereof in the hyaluronic acid composition according to the present invention is particularly Although not limited, 5:95 to 80:20, preferably 10:90 to 70:30 are preferable in terms of mass ratio from the viewpoint of maintaining the moisturizing effect.

  The following components may be further blended in the external preparation for skin according to the present embodiment. Examples of the component include cationized polysaccharides (for example, cationized hydroxyethyl cellulose, cationized guar gum, cationized starch, cationized locust bean gum, cationized dextran, cationized chitosan, and cationized honey), anionic surfactants ( For example, alkylbenzene sulfonate, polyoxyalkylene alkyl ether sulfate, alkyl sulfate, olefin sulfonate, fatty acid salt, dialkyl sulfosuccinate, etc.), nonionic surfactant (eg, polyoxyethylene fatty acid ester, Polyoxyethylene hydrogenated castor oil derivatives, etc.), cationic surfactants (eg alkyl trimethyl ammonium salts, dialkyl dimethyl ammonium salts, alkyl pyridinium salts, stearyl trimethyl chloride) Ammonium), amphoteric surfactants (eg, alkylbetaines, alkylamidopropylbetaines, imidazolinium betaines, egg yolk lecithin, soybean lecithin, etc.), oils (eg, silicone, silicone derivatives, liquid paraffin, squalane, beeswax, carnauba wax, Olive oil, avocado oil, camellia oil, jojoba oil, horse oil, etc.), moisturizer (eg, dimethylsilanol hyaluronate, ceramide, lauroyl glutamate diphytosteryl octyldodecyl, phytoglycogen, hydrolyzed egg shell membrane, trehalose, glycerin, atelocollagen Sorbitol, maltitol, 1,3-butylene glycol, etc.), higher fatty acids (eg, lauric acid, behenic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, etc.), higher Lucol (eg, cetyl alcohol, stearyl alcohol, behenyl alcohol, isostearyl alcohol, batyl alcohol, etc.), polyhydric alcohol (eg, glycerin, diglycerin, 1,3-propanediol, propylene glycol, polyethylene glycol, pentylene glycol, alkane) Diol, etc.), thickener (eg, cellulose ether, carboxyvinyl polymer, xanthan gum, dextrin palmitate, etc.), amphoteric polymer resin compound (eg, betainated dialkylaminoalkyl acrylate copolymer), cationic polymer resin Compound (for example, cationized vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer, polydimethyldiallylammonium halide type cationic polymer), Preservatives (for example, methylparaben, ethylparaben, butylparaben, propylparaben, phenoxyethanol, etc.), antioxidants (for example, tocophenol, BHT, etc.), sequestering agents (for example, edetate, etidronate, etc.), ultraviolet rays Absorbents (eg, benzophenone derivatives, paraaminobenzoic acid derivatives, methoxycinnamic acid derivatives, etc.), ultraviolet reflectors (eg, titanium oxide, zinc oxide, etc.), protein hydrolysates (eg, keratin peptides, collagen peptides, soybean peptides, Wheat peptides, milk peptides, silk peptides, egg white peptides, etc.), amino acids (eg, arginine, glutamic acid, glycine, alanine, hydroxyproline, cysteine, serine, L-theanine, etc.), natural product extracts (kudin extract, kazil extract, te Chica extract, seaweed extract, eucalyptus extract, royal jelly extract, rosemary extract, beech tree extract, etc.) and other functional ingredients (coenzyme Q10, arbutin, polyquaternium 51, elastin, platinum nanocolloid, retinol palmitate, panthenol, allantoin) , Dilauroyl glutamic acid ricin sodium, ascorbyl magnesium phosphate, L-ascorbic acid 2-glucoside, ellagic acid, kojic acid, linoleic acid, tranexamic acid, etc.), phospholipid polymers, fragrances, and pigments.

3. Skin Moisture Content In the present invention, the skin moisture content can be measured by a high-frequency conductance conversion type moisture meter. It is known that the moisture content and conductance of the skin epidermis are highly correlated, and generally the conductance of the epidermis becomes large when the moisture content is high.

4). Examples Hereinafter, the present invention will be described in more detail by way of examples. However, the present invention is not limited to the examples.

4.1. Example 1
4.1.1. Production of hyaluronic acid composition (Preparation of low molecular weight hyaluronic acid)
In this example, a sodium hyaluronate fine powder extracted and purified from a chicken crown was prepared as a raw material. This raw material sodium hyaluronate had an average molecular weight of about 2.1 million and a purity of 97%.

  First, a 300 mL beaker was filled with 110 L of 80% water-containing acetone (acidic water-containing medium) containing 0.5% sulfuric acid and heated so that the liquid temperature became 60 ° C. while stirring. Here, 80% water-containing acetone contains 80 (W / W)% acetone and 20 (W / W)% water, and 80% water-containing acetone containing 0.5% sulfuric acid contains sulfuric acid. It contains 0.5 (W / W)% and contains 99.5 (W / W)% 80% water-containing acetone. After the temperature reached 60 ° C., 6 g of the prepared raw material sodium hyaluronate fine powder was charged into the tank while stirring. While heating so as to maintain the temperature of the sulfuric acid-containing aqueous acetone at 60 ° C., the raw material sodium hyaluronate fine powder was stirred so as to be in a dispersed state.

  Next, after stirring for 15 minutes and allowing to stand, the supernatant sulfuric acid-containing water-containing acetone was removed by decantation to obtain a precipitate. To the resulting precipitate, 110 mL of 0.5% sulfuric acid-containing 80% water-containing acetone previously heated to 60 ° C. was added, and similarly stirred for 15 minutes while heating to 60 ° C. This operation was repeated a total of 3 times.

  Next, 110 mL of 80% aqueous acetone was added to the precipitate obtained after removing the sulfuric acid-containing aqueous acetone, and the mixture was stirred for 15 minutes for the purpose of removing sulfuric acid. This operation was repeated until no sulfuric acid remained.

  Furthermore, water-containing acetone was removed by decantation to obtain a residue. The residue was further centrifuged to remove water-containing acetone, and then the solvent was removed using a vacuum dryer at room temperature for 6 hours.

Through the above steps, 5.3 g (yield: about 88%) of low molecular weight hyaluronic acid as white fine powder was obtained. This low-molecular hyaluronic acid had a kinematic viscosity of 1 mm aqueous solution measured using an Ubbelohde viscometer of 1.5 mm ² / s, and a molecular weight calculated from the intrinsic viscosity was 9,000.

(Preparation of cationized hyaluronic acid)
In a 1 L beaker, 20 g of sodium hyaluronate (manufactured by Kewpie Corporation, average molecular weight 2 million), 20 mL of 5% sodium hydroxide, 180 mL of 80% water-containing ethanol, and glycidyltrimethylammonium chloride (GTA (active ingredient about 80%, moisture about 20%)) 30 mL was added and reacted for 1 hour at 40 ° C. with stirring using a stir bar.
Next, the liquid was removed by decantation to obtain a solid (including cationized hyaluronic acid).

  Next, 400 mL of brine was added to dissolve the solid. After confirming that the solid was completely dissolved, 600 mL of ethanol was added to precipitate cationized hyaluronic acid. After removing the liquid by decantation, 500 mL of 80% aqueous ethanol was added and stirred for 15 minutes, and the aqueous ethanol was then removed by decantation to obtain a precipitate. This operation was repeated three times to remove the cationizing agent (GTA) and sodium chloride remaining in the precipitate.

Next, the water-containing ethanol was further removed by performing a centrifugal separation treatment, followed by heat drying at 60 ° C. under reduced pressure for 5 hours using a vacuum dryer.
As a result, 20.5 g of cationized hyaluronic acid as a white powder was obtained. The nitrogen content of this cationized hyaluronic acid was measured, and the degree of cationization determined by the above formula was 0.27.

(Production of hyaluronic acid composition)
The low molecular hyaluronic acid obtained by the above method and cationized hyaluronic acid were mixed by powder so that the content ratio was 50:50 by mass ratio to obtain the hyaluronic acid composition of the present invention.

4.1.2. Test example 1
The hyaluronic acid composition of the present invention was transdermally administered to humans, and the durability of the moisturizing effect was evaluated. More specifically, the hyaluronic acid composition of the present invention was applied to the upper arm of the subject, the moisture content of the skin after 24 hours was measured, and compared with the control (hyaluronic acid alone).

4.1.3. Used sample test solution 1: 1% aqueous solution test solution of hyaluronic acid composition obtained in Example 1 2: 1% aqueous solution test solution of hyaluronic acid with molecular weight of 1,200,000 (manufactured by QP Corporation) 3: Acetylated hyaluronic acid In addition, the said test liquid 1 was melt | dissolving in water, without producing a precipitate.

4.1.4. Measuring equipment Moisture content measuring device: trade name “SKICON-200”, I.D. B. S. Co. The amount of change in the amount of skin moisture at each time when the measured value of the amount of skin moisture before application of the sample was 0 was calculated.

After washing the forearm of the right arm of subjects (10 adults: 5 men, 5 women) with soap, set a sample application area of 2 cm x 2 cm, in an environment of room temperature 20-25 ° C and humidity 45-55% After resting for 20 minutes, the skin moisture content before the sample application was measured. Then, each 20 microliters of test solutions 1-3 were apply | coated uniformly, and the moisture content of the skin of an application | coating site | part was measured with the moisture content measuring device. The moisture content was measured immediately before coating, 20 minutes, 40 minutes, 120 minutes, 240 minutes, 360 minutes, and 24 hours after coating. The measurement was performed four times for each area.
The results are shown in Table 1. The numerical values shown in Table 1 are the amount of change in skin moisture, and the amount of change in skin moisture when the amount of skin moisture immediately before application is zero. Moreover, the numerical value shown in Table 1 is an average numerical value of 10 subjects. In addition, a multiple comparison test by Fisher's PLSD method was performed at each time, and it was determined that there was a significant difference at a risk rate p <0.05.

  According to Table 1, it was confirmed that when the test solution 1 was applied, the amount of moisture in the skin could be retained more than when the test solutions 2 and 3 were applied.

4.2. Example 2
Example 2 was obtained by mixing hyaluronic acid having a molecular weight of 1.8 million with the hyaluronic acid composition obtained in Example 1 so as to have the following ratio.

Hyaluronic acid composition of Example 2 50 parts of hyaluronic acid composition of Example 1 50 parts of hyaluronic acid with a molecular weight of 1.8 million

4.3. Example 3
Example 3 was obtained by mixing hyaluronic acid having a molecular weight of 1.8 million with the hyaluronic acid composition obtained in Example 1 so as to have the following ratio.

Hyaluronic acid composition of Example 3 Hyaluronic acid composition of Example 1 60 parts Hyaluronic acid with a molecular weight of 1.8 million 40 parts

4.4. Test example 2
In the same manner as in Test Example 1, the hyaluronic acid composition of the present invention was transdermally administered to humans, and the durability of the moisturizing effect was evaluated.

4.4.1. Sample test solution 4: 0.1% aqueous solution test solution of hyaluronic acid composition obtained in Example 2 5: 0.1% aqueous solution test solution of hyaluronic acid composition obtained in Example 3 6: Molecular weight 1,200,000 0.1% aqueous solution of hyaluronic acid (manufactured by QP Corporation) The test solutions 4 and 5 were dissolved in water without causing precipitation.

4.4.2. Measuring equipment Moisture content measuring device: trade name “SKICON-200”, I.D. B. S. Co. Made by LTD

After washing the left arm forearm of subjects (14 adults: 9 males and 5 females) with soap, a 2 cm x 2 cm sample application area is set, and the room temperature is 20-25 ° C and the humidity is 45-55%. After resting for 20 minutes, the skin moisture content before the sample application was measured. Then, each 20 microliters of test solutions 4-6 were apply | coated uniformly, and the moisture content of the skin of the application | coating site | part was measured with the moisture content measuring device. The moisture content was measured immediately before application, and at the time when 10 minutes, 20 minutes, 40 minutes, 60 minutes, and 120 minutes had elapsed after application. The measurement was performed 8 times for each area, and an average of 6 times excluding the maximum value and the minimum value was adopted.
The results are shown in Table 2. The numerical values shown in Table 2 are the amount of change in skin moisture, and the amount of change in skin moisture when the amount of skin moisture immediately before application is zero. Moreover, the numerical value shown in Table 2 is an average numerical value of 14 subjects. At each time, Dunnett's multiple comparison test was performed for comparison with the time before application, and Tukey's multiple comparison test was performed for comparison between groups, and it was determined that there was a significant difference at a risk rate p <0.05.

  According to Table 2, it was confirmed that when the test solutions 4 and 5 were applied, the amount of moisture in the skin could be retained more than when the test solution 6 was applied.

4.5. Example 4
In this example, lotion was prepared as a skin external preparation formulated with the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.2%
Acetylated hyaluronic acid 0.1%
Chondroitin sulfate 0.1%
Collagen peptide 0.1%
1,3-butylene glycol 5.0%
Glycerol 3.0%
Isostearyl alcohol 0.1%
Tocopherol acetate 0.1%
POE (20) sorbitan monolaurate 0.5%
POE (15) lauryl alcohol ether 0.5%
Zinc pyrrolidonecarboxylate 0.1%
Ethylparaben 0.1%
Methylparaben 0.15%
Ethanol 5.0%
Perfume Appropriate amount Purified water Remaining

4.6. Example 5
In this example, an emulsion was prepared as an external preparation for skin containing the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.3%
Pentylene glycol 5.0%
Glycerol 3.0%
Squalane 5.0%
Stearic acid 0.5%
Stearyl alcohol 2.0%
Vaseline 4.0%
Sorbitan stearate 1.0%
POE (10) monostearate 1.0%
Carboxy vinyl polymer 0.5%
Polyquaternium-51 0.1%
Methylparaben 0.15%
Propylparaben 0.1%
Potassium hydroxide 0.1%
BHT 0.02%
EDTA-2 sodium 0.02%
Perfume Appropriate amount Purified water Remaining

4.7. Example 6
In this example, a cream (emollient cream) was prepared as a skin external preparation containing the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.5%
Polyethylene glycol 4.0%
1,3-propanediol 6.0%
Squalane 11.0%
Dimethicone 1.0%
Cetanol 6.0%
Stearic acid 2.0%
Hydrogenated cocoglyceryl 4.0%
Tricaprylin 8.0%
Glycerol monostearate 3.0%
POE (20) cetyl alcohol ether 2.0%
Coenzyme Q10 0.03%
Ceramide 0.1%
Dilauroyl glutamate ricin sodium 0.1%
EDTA-2 sodium 0.02%
Propylparaben 0.1%
Methylparaben 0.15%
Perfume Appropriate amount Purified water Remaining

4.8. Example 7
In this example, a cosmetic liquid (whitening moisturizing essence) was prepared as an external preparation for skin containing the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.8%
1,3-butylene glycol 5.0%
Glycerin 1.5%
POE sorbitan monostearate 1.0%
Sorbitan monostearate 0.5%
Xanthan gum 0.2%
Sodium alginate 0.2%
Carboxyvinyl polymer 0.2%
Potassium hydroxide 0.1%
Olive oil 0.2%
Tocopherol 0.1%
EDTA-2 sodium 0.02%
Arginine 0.15%
Dipotassium glycyrrhizinate 0.05%
Arbutin 0.2%
Retinol palmitate 0.2%
Cousin extract 0.2%
Seaweed extract 0.2%
Tranexamic acid 0.1%
Elastin 0.1%
Collagen 0.1%
Magnesium phosphate ascorbate 0.1%
Sodium citrate 1.0%
Citric acid 0.1%
Propylparaben 0.1%
Methylparaben 0.15%
Perfume Appropriate amount Purified water Remaining

4.9. Example 8
In this example, a cosmetic liquid pack (paste peel-off type) was prepared as a skin external preparation formulated with the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.5%
Polyvinyl acetate emulsion 17.0%
Polyvinyl alcohol 11.0%
Sorbitol 5.0%
Polyethylene glycol 400 5.0%
Squalane 2.5%
POE sorbitan monostearate 1.0%
Titanium oxide 4.0%
Talc 8.0%
Ethanol 8.0%
Methylparaben 0.15%
Perfume Appropriate amount Purified water Remaining

4.10. Example 9
In this example, a face wash (cleansing foam) was prepared as a skin external preparation formulated with the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.2%
Glycerin 10.0%
Polyethylene glycol 400 15.0%
Dipropylene glycol 10.0%
Sodium lauroyl glutamate 20.0%
POE (2) monostearate 5.0%
Palm fatty acid sodium glutamate 8.0%
Alkyl betaine 2.0%
EDTA-2 sodium 0.02%
Propylparaben 0.1%
Methylparaben 0.15%
Perfume Appropriate amount Purified water Remaining

4.11. Example 10
In this example, a sunscreen (milky lotion) was prepared as an external preparation for skin containing the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.2%
1,3-butylene glycol 3.0%
Dipropylene glycol 3.0%
Cyclomethicone 5.0%
Dimethicone 5.0%
Cetanol 1.0%
Vaseline 1.0%
Octyl methoxycinnamate 5.0%
Titanium oxide 2.0%
Zinc oxide 2.0%
Sorbitan stearate 1.0%
POE (20) sorbitan monostearate 1.0%
Phenoxyethanol 0.8%
Methylparaben 0.1%
Perfume appropriate amount Purified water remaining

4.12. Example 11
In this example, a lip balm was prepared as a skin external preparation containing the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.1%
Microcrystalline wax 1.5%
Ceresin 12.0%
Squalane 10.0%
Decamethyltetrasiloxane 10.0%
Diisostearyl malate 5.0%
Candelilla wax 2.0%
Vaseline 8.0%
Glyceryl hydroxystearate 2.0%
Menthol 0.05%
Liquid paraffin 1.0%
Tocopherol acetate 0.1%
Tocopherol 0.05%
Propylparaben 0.1%
Perfume Appropriate amount Purified water Remaining

4.13. Example 12
In this example, a shampoo was prepared as a skin external preparation formulated with the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.2%
POE (20) sodium lauryl ether sulfate 11.0%
Lauroyl sodium aspartate 10.0%
Coconut oil fatty acid amidopropyl betaine 4.0%
Coconut oil fatty acid monoethanolamide 2.0%
EDTA-2 sodium 0.1%
Sodium benzoate 0.2%
Phenoxyethanol 0.8%
Methylparaben 0.1%
Perfume appropriate amount Purified water remaining

4.14. Example 13
In this example, a hair conditioner was prepared as a skin external preparation formulated with the hyaluronic acid composition obtained in Example 1 according to the formulation described below.
Hyaluronic acid composition (Example 1) 0.3%
Stearyl alcohol 4.0%
Cetanol 1.5%
Hydroxyethyl urea 1.0%
Aminopropyl dimethicone 1.5%
Dimethicone 0.5%
Hydrolyzed silk 1.0%
1,3-butylene glycol 1.0%
Glycerol 3.0%
Cetyl 2-ethylhexanoate 2.0%
Isocetyl myristate 0.4%
L-Arginine 0.1%
Trehalose 0.1%
Sorbitol 0.1%
Keratin peptide 0.1%
POE (4) stearyl ether 1.0%
Stearic acid dimethylaminopropylamide 3.0%
Distearyldimethylammonium chloride 0.2%
Sodium benzoate 0.3%
Phenoxyethanol 0.8%
Methylparaben 0.1%
Perfume Appropriate amount Purified water Remaining

Claims (5)

A hyaluronic acid composition having a mass ratio of a low molecular weight hyaluronic acid and / or salt thereof having a mean molecular weight of 100,000 or less and a cationized hyaluronic acid and / or salt thereof in a mass ratio of 5:95 to 80:20, ,
An aqueous solution of the hyaluronic acid composition prepared by adding the low molecular weight hyaluronic acid and / or salt thereof and the cationized hyaluronic acid and / or salt thereof to a total amount of 1% by mass in terms of hyaluronic acid produces a precipitate. A hyaluronic acid composition characterized by being dissolved in water.   The hyaluronic acid composition according to claim 1, wherein the low-molecular-weight hyaluronic acid and / or a salt thereof has an average molecular weight of 400 to 50,000.   The composition according to claim 1 or 2, further comprising hyaluronic acid having an average molecular weight exceeding 100,000 and / or a salt thereof.   The skin external preparation containing the hyaluronic acid composition of any one of Claims 1 thru | or 3. A method for increasing the amount of skin moisture using the hyaluronic acid composition according to any one of claims 1 to 3.