JP2009051877A - New hyaluronic acid and/or salt thereof, food composition and oral medicinal composition using the same, and oral skin ameliorating agent or oral skin water content-increasing agent comprising the hyaluronic acid and/or the salt thereof as active ingredient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new hyaluronic acid and/or a salt thereof, to provide a food composition and an oral medicinal composition using the same and to provide an oral skin ameliorating agent and an oral skin water content-increasing agent comprising the hyaluronic acid and/or the salt thereof as an active ingredient. <P>SOLUTION: The hyaluronic acid and/or the salt thereof have ≥1,000 to <5,000 average molecular weight thereof. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to a novel hyaluronic acid and / or salt thereof having an action of increasing the moisture content of the skin and improving the skin by ingestion, a food composition and an oral pharmaceutical composition using the same, and the The present invention relates to an oral skin improving agent or an oral skin moisture content increasing agent containing hyaluronic acid and / or a salt thereof as an active ingredient.

Hyaluronic acid (average molecular weight: 500,000 to 2,000,000) is a mucopolysaccharide that is present in many tissues in the living body (for example, subcutaneous tissue, eyeballs, joints). It has been widely used. In addition, by ingesting hyaluronic acid, it is recognized that the effect of improving the moisture retention, elasticity, and flexibility of the skin is compensated for by reducing the natural hyaluronic acid content (for example, Japanese Patent Application Laid-Open No. 2002-2002). No. 356432), hyaluronic acid and its salts are added to various foods.

However, it has not been studied so far what effect is produced on the skin by ingesting low molecular weight hyaluronic acid having an average molecular weight of 10,000 or less.
JP 2002-356432 A

An object of the present invention is to provide a novel hyaluronic acid and / or salt thereof having an effect of increasing the moisture content of the skin by oral ingestion and improving the skin, and a food composition and an oral pharmaceutical composition using the same, and The present invention provides an oral skin improving agent or oral skin water content increasing agent containing the hyaluronic acid and / or salt thereof as an active ingredient.

As a result of intensive research on low molecular weight hyaluronic acid, the present inventor surprisingly, if hyaluronic acid and / or a salt thereof having a specific average molecular weight and molecular weight distribution is orally ingested, the water content of the skin is surprisingly low. It has been found that it increases and improves the skin, and the present invention has been completed.

That is, the present invention
(1) Hyaluronic acid and / or a salt thereof having an average molecular weight of 1,000 or more and less than 5,000,
(2) The hyaluronic acid according to (1), wherein the molecular weight distribution is such that the proportion of components having a molecular weight of 1,000 or more is 40% by mass or more and the proportion of components having a molecular weight of 5,000 or more is 40% by mass or less. / Or its salt,
(3) Hyaluronic acid and / or a salt thereof according to (1) or (2), wherein the proportion of components having a molecular weight distribution of less than 1,000 is 20% by mass or more,
(4) Absorbance (A) of a solution obtained by adding 0.5 g / mL aqueous cetylpyridinium chloride solution (0.05 g) to 0.1 g / mL aqueous solution (10 mL) of the hyaluronic acid and / or its salt ₆₆₀ ) is 0.1 Abs or less, the hyaluronic acid and / or salt thereof according to any one of (1) to (3),
(5) The hyaluronic acid and / or salt thereof according to any one of (1) to (4), obtained by hydrolyzing hyaluronic acid and / or a salt thereof in an acidic aqueous solution,
(6) A food composition containing the hyaluronic acid and / or salt thereof according to any one of (1) to (5),
(7) An oral pharmaceutical composition containing the hyaluronic acid and / or salt thereof according to any one of (1) to (5),
(8) An oral skin improving agent containing the hyaluronic acid and / or salt thereof according to any one of (1) to (5) as an active ingredient,
(9) An oral skin moisture content increasing agent comprising the hyaluronic acid and / or salt thereof according to any one of (1) to (5) as an active ingredient,
It is.

According to the hyaluronic acid and / or salt thereof of the present invention, by taking orally, the moisture content of the skin is increased, the moisture content of the skin is increased, and the skin can be refreshed.

Hereinafter, hyaluronic acid and / or a salt thereof according to an embodiment of the present invention will be described in detail. In the present invention, “%” means “mass%”.

The hyaluronic acid and / or salt thereof of the present invention has an average molecular weight of 1,000 or more and less than 5,000.

Here, “hyaluronic acid” refers to a polysaccharide having one or more repeating structural units composed of disaccharides of glucuronic acid and N-acetylglucosamine. The “hyaluronic acid salt” is not particularly limited, but is preferably a food or pharmaceutical acceptable salt, for example, sodium salt, potassium salt, calcium salt, zinc salt, magnesium salt, ammonium salt, etc. Is mentioned.

The average molecular weight of the hyaluronic acid or a salt thereof of the present invention is 1,000 or more and less than 5,000. Moreover, 1,000 or more and 3,000 or less are preferable and more preferably 1,000 or more and 2,000 or less from the viewpoint of the superiority of the effect of increasing the moisture content of the skin. This is because if the average molecular weight of hyaluronic acid or a salt thereof is larger than the above value, the effect of increasing the moisture content of the skin by oral intake of the hyaluronic acid and / or a salt thereof is small. When the average molecular weight of hyaluronic acid or a salt thereof is smaller than the above value, a decomposition process for preparing the hyaluronic acid and / or a salt thereof takes a long time and is not economical.

The hyaluronic acid and / or salt thereof used in the present invention has a molecular weight distribution in which the proportion of components having a molecular weight of 1,000 or more is 40% or more and the proportion of components having a molecular weight of 5,000 or more is 40% or less. Preferably, the proportion of components having a molecular weight of less than 1,000 is 20% or more. Further, in terms of the superiority of the effect of increasing the moisture content of the skin, the proportion of components having a molecular weight of less than 1,000 is 30% or more, and the proportion of components having a molecular weight of 5,000 or more is 20% or less. More preferably, the proportion of components having a molecular weight of less than 1,000 is 40% or more, and the proportion of components having a molecular weight of 5,000 or more is more preferably 10% or less. By using hyaluronic acid and / or a salt thereof having such a molecular weight distribution, the moisture content of the skin can be effectively increased, particularly when taken orally.

The measurement method of the average molecular weight and molecular weight distribution prescribed | regulated by this invention is demonstrated.

The average molecular weight and molecular weight distribution defined in the present invention can be obtained by liquid chromatography analysis of hyaluronic acid and / or a salt thereof using a gel filtration column. Hyaluronic acid and / or a salt thereof is a mixture of a plurality of components having different molecular weights depending on the number of repeating structural units (N-acetyl-D-glucosamine and D-glucuronic acid). Accordingly, by performing liquid chromatography analysis on an aqueous solution of hyaluronic acid and / or a salt thereof using a gel filtration column, the components constituting hyaluronic acid and / or the salt thereof can be separated by molecular size.

The average molecular weight and molecular weight distribution of hyaluronic acid and / or a salt thereof in the present invention were measured with an HPLC analyzer (trade name “Alliance PDA System”, manufactured by Nihon Waters Co., Ltd.) and a gel filtration column (trade name “Diol-120”, stocks). And a 0.1% (w / v) aqueous solution of hyaluronic acid and / or a salt thereof as an analysis sample, and this analysis sample can be measured by liquid chromatography analysis.

The conditions for liquid chromatography analysis are as follows.
Column temperature: 40 ° C
Flow rate: 1 mL / min Injection volume of 0.1% (w / v) aqueous solution of hyaluronic acid and / or its salt: 20 μL
Mobile phase: 0.003 mol / L phosphate buffer (containing 0.15 mol / L NaCl, pH 7.0)
Ultraviolet detector: measured at λ = 210 nm In the liquid chromatography using the gel filtration column according to the present invention, the longer the retention time, the lower the molecular weight. In order of decreasing retention time, N-acetylglucosamine, D-glucuronic acid, hyaluronic acid (disaccharide: one repeating structural unit), hyaluronic acid (tetrasaccharide: two repeating structural units), hyaluronic acid (hexasaccharide: repeating structure) Peaks of 3 units), hyaluronic acid (octasaccharide: 4 repeating structural units)... Are obtained.

As an example, Table 1 shows the relationship between the number of repeating units of each molecular weight component obtained from the chromatogram shown in FIG.

The average molecular weight defined in the present invention is calculated by determining the proportion of components having a predetermined molecular weight by dividing the peak by the retention time corresponding to the predetermined molecular weight. The molecular weight indicated by each peak is referred to the peak in the chromatogram obtained by liquid chromatography analysis of the smallest structural unit (disaccharide) of hyaluronic acid and / or its salt with a known molecular weight in the same manner. To be identified. The average molecular weight can be obtained by calculating the product of the predetermined molecular weight and the ratio (area%) of the component having the predetermined molecular weight for each peak and calculating the sum of the products for all the peaks.

In the molecular weight distribution defined in the present invention, a peak is divided by a retention time corresponding to a predetermined molecular weight (1,000 or 5,000), thereby obtaining a ratio of components in a predetermined molecular weight range.

For example, the ratio of components having a molecular weight of 1,000 or more can be obtained by dividing the absorption area of the component before the retention time corresponding to the molecular weight of 1,000 by the total absorption area. Similarly, the ratio of components having a molecular weight of 5,000 or more can be determined by dividing the absorption area of the component before the retention time corresponding to the molecular weight of 5,000 by the total absorption area.

The hyaluronic acid and / or salt thereof of the present invention is characterized in that precipitation or turbidity due to binding with cetylpyridinium chloride (CPC) does not occur. The CPC precipitation method is a test method used as a confirmation test for mucopolysaccharides. Mucopolysaccharides typified by hyaluronic acid are known to cause precipitation by binding to quaternary ammonium salts such as CPC. In the present invention, the liquid obtained by the CPC precipitation method can be used as one of indices for evaluating the characteristics of the low molecular hyaluronic acid and / or salt thereof of the present invention.

The hyaluronic acid and / or salt thereof according to the present embodiment is prepared by adding 0.5 g / mL CPC aqueous solution (0.05 g) to 0.1 mg / mL aqueous solution (10 mL) of the above low-molecular hyaluronic acid and / or salt thereof. The absorbance (A ₆₆₀ ) of the liquid obtained by addition is preferably 0.1 Abs or less. That is, the absorbance (A ₆₆₀ ) is the absorbance with respect to light having a wavelength of 660 nm, and is widely used as an index for identifying “turbidity” of the liquid.

Here, the hyaluronic acid and / or salt thereof according to this embodiment does not form a precipitate and does not cause white turbidity when the above mixed solution is prepared due to the characteristics of the molecular weight and molecular weight distribution. That is, the absorbance value is an index indicating the characteristics of hyaluronic acid and / or a salt thereof according to the present embodiment.

A typical method for producing the hyaluronic acid and / or salt thereof used in the present invention will be described below. In addition, the manufacturing method of hyaluronic acid and / or its salt used by this invention is not limited to this.

The hyaluronic acid and / or salt thereof (hereinafter also referred to as “raw hyaluronic acid and salt thereof”), which is a raw material of the hyaluronic acid and / or salt thereof, is generally a biological tissue such as a chicken crown, umbilical cord, eyeball, skin, cartilage, Alternatively, it can be obtained by using a culture solution obtained by culturing a hyaluronic acid-producing microorganism such as a microorganism belonging to the genus Streptococcus as a raw material, and extracting (and purifying as necessary) these raw materials. For example, the molecular weight of the raw material hyaluronic acid and / or its salt extracted from a chicken crown is usually 2 million to 8 million.

The molecular weight of the hyaluronic acid and / or salt thereof can be reduced by hydrolyzing the raw material hyaluronic acid and / or salt thereof with an acid, alkali, enzyme, or the like. Preferably it is done. By hydrolyzing hyaluronic acid and / or a salt thereof in an acidic aqueous solution, hyaluronic acid and / or a salt thereof free from browning can be obtained economically. Here, the degree of low molecular weight can be adjusted by adjusting the stirring speed and stirring time during hydrolysis. Further, by performing the hydrolysis step described above under heating conditions, the molecular weight can be stably reduced to the target molecular weight. For example, the raw material hyaluronic acid and / or a salt thereof can be added to an aqueous solution containing acid, alkali, enzyme, and the like while stirring, and the resulting aqueous solution can be heated. Or the aqueous solution containing an acid, an alkali, an enzyme, etc. may be heated beforehand, and raw material hyaluronic acid and / or its salt may be added to this, and temperature may be maintained.

In the said manufacturing method, hydrochloric acid, a sulfuric acid, an acidic cation exchange resin etc. are mentioned as an acid used in order to perform a hydrolysis. Examples of the alkali include sodium hydroxide and potassium hydroxide. Examples of the enzyme include hyaluronidase.

In the above production method, when hydrolyzing hyaluronic acid and / or a salt thereof in an acidic aqueous solution, the pH is preferably 0.6 or less, more preferably 0.4 or less, so that hydrolysis can be performed particularly efficiently. The hyaluronic acid and / or salt thereof of the present invention can be obtained in a short time compared to other methods.

In the above production method, the acidic aqueous solution refers to a solution in which hyaluronic acid and / or a salt thereof is dissolved in a liquid containing water and an acid. The other components contained in the acidic aqueous solution are not particularly limited. However, for example, those which are liquid and have a property of being dissolved in water and can be used in the manufacturing process of pharmaceuticals or foods are preferable. For example, alcohol media (for example, methanol, ethanol, n-propyl alcohol, isopropyl alcohol, etc.), ketone media (for example, acetone, methyl ethyl ketone, etc.), tetrahydrofuran, acetonitrile, etc. can be mentioned, and these can be used alone or in combination. Can be used.

The method for converting hyaluronic acid into a hyaluronic acid salt and the method for converting the hyaluronic acid salt into hyaluronic acid are not particularly limited. As a method for converting the above hyaluronic acid into a hyaluronic acid salt, for example, an alkaline aqueous solution (for example, an aqueous solution of sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide, etc.) is used. The method of doing is mentioned. Examples of the method for converting the salt of hyaluronic acid into hyaluronic acid include, for example, a method using an aqueous acid solution (for example, an aqueous solution of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc.), an acidic cation exchange resin, and the like. The method using is mentioned.

The food composition which concerns on one Embodiment of this invention contains the said hyaluronic acid and / or its salt. The form of the food composition is not particularly limited, but for example, gum, candy, gummy candy, troche-like food, jelly beverage, cooked rice food, bread making, canned retort, frozen food, side dish, dried food, mayonnaise, etc. General foods such as foods, beverages, confectionery, desserts, and supplements, and foods for specified health use that are permitted to express physiological functions. When the food composition contains the hyaluronic acid and / or a salt thereof, an effect of increasing the moisture content of the skin can be exhibited by ingesting the food composition.

About 0.001-50% is preferable and the said hyaluronic acid and / or its salt mix | blended in the foodstuff composition which concerns on one Embodiment of this invention has more preferable about 0.005-30%. If the blending amount of hyaluronic acid and / or a salt thereof is more than the above range, the flavor of hyaluronic acid and / or a salt thereof becomes strong, and the original taste of the food composition may be impaired. On the other hand, if the amount is less than the above range, the effect of increasing the moisture content of the skin of hyaluronic acid and / or its salt hardly appears and the commercial value is lowered, which is not preferable.

An oral pharmaceutical composition according to an embodiment of the present invention contains the hyaluronic acid and / or salt thereof as an active ingredient. Although the aspect of the said oral pharmaceutical composition is not specifically limited, An internal use etc. are mentioned, For example, a tablet, a capsule, a powder, a granule, a troche, an internal use liquid agent, a syrup agent, a chewable agent, an emulsion etc. are mentioned. When the oral pharmaceutical composition contains the hyaluronic acid and / or salt thereof as an active ingredient, by taking the oral pharmaceutical composition orally, the moisture content of the skin is increased and the skin is refreshed. The effect to improve can be exhibited.

The intake amount of the oral skin improving agent or oral skin water content increasing agent of the present invention is preferably 10 to 2,000 mg / day, more preferably 50 to 500 mg / day, as hyaluronic acid and / or a salt thereof. If the intake amount of the hyaluronic acid exceeds the above range, the intake amount that effectively increases the moisture content of the skin may be exceeded, which is not economical. On the other hand, if it is less than the above range, hyaluronic acid and / or a salt thereof has an effect of increasing the moisture content of the skin and an effect of improving the skin, which is not preferable because the commercial value is lowered.

As the oral skin improvement agent and oral skin water content increasing agent of the present invention, the hyaluronic acid and / or its salt is preferably used as an oral skin improving agent or oral skin water content increasing agent as it is. Solvents such as dextrin, excipients such as dextrin, and other food or pharmaceutically acceptable raw materials may be added. In that case, the content of the hyaluronic acid and / or a salt thereof is preferably 0.1% or more, more preferably 1% or more, in consideration of the blending amount in food or pharmaceuticals and ease of blending.

Hereinafter, hyaluronic acid and / or a salt thereof having an average molecular weight of 1,000 or more and less than 5,000 used in the present invention will be specifically described based on Examples and the like. The present invention is not limited to these.

[Preparation Example 1]
In this preparation example, a sodium hyaluronate (hereinafter also referred to as “HANa”) fine powder extracted and purified from a chicken crown was prepared as a raw material. The raw material HANa had an average molecular weight of about 2.1 million and a purity of 97%.

First, a 500 L tank equipped with a stirrer and a jacket was filled with 200 L of distilled water, and 18 kg of 35% hydrochloric acid was added to adjust the pH to 0.3. While stirring, the liquid temperature was heated to 70 ° C. After the temperature reached, 11.5 kg of the prepared raw material HANa fine powder was charged into the tank while stirring. The raw material HANa fine powder was dissolved while heating to maintain the liquid temperature at 70 ° C.

Next, after stirring for 7 hours, the hyaluronic acid solution was cooled to stop the decomposition reaction in the acidic aqueous solution. The resulting hyaluronic acid solution was neutralized to pH 7 with a 20% aqueous sodium hydroxide solution.

Next, the neutralized solution was desalted and then spray-dried to obtain 7.5 kg of white fine powder sodium hyaluronate (yield: about 65%). This sodium hyaluronate had an average molecular weight of 1,100, and in the molecular weight distribution, the proportion of components having a molecular weight of 1,000 or more was 47% and the proportion of components having a molecular weight of 5,000 or more was 0%. Moreover, the ratio of the component with a molecular weight of less than 1,000 was 53%. The absorbance (A ₆₆₀ ) of the liquid obtained by adding 0.5 mg / mL aqueous cetylpyridinium chloride solution (0.05 g) to 0.1 g / mL aqueous solution (10 mL) of the obtained sodium hyaluronate is 0.01 Abs.

[Test Example 1]
In this test example, the sodium hyaluronate of the present invention was orally administered to mice and the effect on the skin was examined.

The mouse used was a male C57BL / 6N mouse (SPF) 6 weeks old (purchased from Japan Charles River Co., Ltd.). The mice were trained for 6 days after loading and used for the test.

The following three types of samples were used.
Sample 1: Sodium hyaluronate obtained in Preparation Example 1 (average molecular weight 1,100)
Sample 2: hyaluronic acid (average molecular weight 30,000)
Sample 3: distilled water (control)
Sample 2 was a commercially available product, and the molecular weight was determined according to a conventional method by measuring kinematic viscosity.

The weights of the mice after habituation were measured and divided into the following three groups using the weight as an index.
Sample group 1: Group 1 that ingests 200 mg / kg / day of sample 1 Sample group 2: Group that ingests 200 mg / kg / day of sample 2 Sample group 3: Group that ingests distilled water (control) 5 animals

First, samples 1 and 2 were dissolved in distilled water to 1.1 g / L, and 3 mL (200 mg / kg / day as hyaluronic acid) of this sample aqueous solution was orally administered to each sample group per day. did. Sample group 3 was orally administered with 3 mL of distilled water per day. After a 14-day administration test, the mice were laparotomized and blood was collected from the posterior aorta and euthanized after blood collection. Next, the entire skin layer of the back of the mouse was collected, and using biopsy trepan (tip diameter φ8 mm), two locations were collected per mouse so that the entire skin layer had the same size (unit area: 100). .5 mm ² ).

About the obtained skin full-thickness sample, skin thickness, wet skin weight, dry skin weight, skin moisture weight, and hyaluronic acid concentration in the skin were measured. Skin thickness was measured using a micrometer. The dry skin weight was determined by measuring the wet skin weight, freeze-drying the skin, and measuring the dry skin weight and dry skin weight. Hyaluronic acid concentration in the skin was measured by a microtiter assay method using hyaluronic acid binding protein (HABP) after proteolytic enzyme treatment after the skin was homogenized, hyaluronic acid was extracted and filtered. .

The obtained blood was allowed to stand for 1 hour and then centrifuged at 3,000 rpm for 15 minutes to collect serum. This was ultrafiltered, treated with a proteolytic enzyme, filtered, and then the hyaluronic acid concentration in serum was measured by a microtiter assay using hyaluronic acid binding protein (HABP).

The average value of the measurement results was calculated for each sample group. Table 2 shows the measured values of sample groups 1 to 3 and the average values of sample groups 1 and 2 when the average value of sample group 3 is 100.

From Table 2, the mice in sample group 1 have almost the same serum hyaluronic acid concentration as compared to mice in sample groups 2 and 3, while the hyaluronic acid concentration in skin, skin thickness, skin wet weight, skin The dry weight and skin moisture weight increased. Therefore, it was found that by taking orally ingesting sodium hyaluronate of Sample 1, the skin weight, the moisture weight in the skin, and the thickness of the skin are effectively increased.

[Preparation Example 2]
In the same manner as in Preparation Example 1, HANa was hydrolyzed in an acidic aqueous solution and cooled after stirring for 2 hours from the start of the reaction to stop the decomposition reaction. Next, the hyaluronic acid solution was freeze-dried, and the obtained hyaluronic acid-containing dried product was returned to the 500 L tank. 200 L of 80% water-containing ethanol was added thereto, and stirring was performed for 15 minutes for the purpose of removing hydrochloric acid. Here, 80% water-containing ethanol contains 80% ethanol and 20% water. After stirring for 15 minutes, the mixture was allowed to stand, and the supernatant water-containing ethanol was removed by decantation to obtain a residue. This operation was repeated until no hydrochloric acid remained.

The residue after removal of hydrochloric acid was further centrifuged to remove water-containing ethanol, and then dried for 12 hours at room temperature in the presence of silica gel under reduced pressure using a vacuum dryer. Through the above steps, 7.9 kg of white fine powder hyaluronic acid (yield: about 69%) was obtained. This hyaluronic acid has an average molecular weight of 4,600, and in the molecular weight distribution, the proportion of components having a molecular weight of 1,000 or more is 94%, the proportion of components having a molecular weight of 5,000 or more is 37%, The component having a molecular weight of less than 1,000 was 6%. In addition, the absorbance (A ₆₆₀ ) of the liquid obtained by adding 0.5 g / mL aqueous cetylpyridinium chloride solution (0.05 g) to 0.1 g / mL aqueous solution (10 mL) of the obtained hyaluronic acid was 0. 0.06 Abs.

[Test Example 2]
Using the sodium hyaluronate obtained in Preparation Example 1, a jelly beverage having the following composition was produced. The flavor and texture of the obtained jelly beverage were good.
<Combination ratio>
Sodium hyaluronate from Preparation Example 0.05%
Pear fruit juice (concentrated and reduced) 10.0%
Glucose fructose liquid sugar 8.0%
Sweetener 0.1%
Acidulant 0.3%
Gelling agent 0.7%
Pear fragrance 0.1%
Remaining amount of purified water ――――――――――――――――――――――――
100%

[Test Example 3]
Using the hyaluronic acid obtained in Preparation Example 2, a soft drink having the following composition was produced. The flavor of the obtained soft drink was good.
<Combination ratio>
Hyaluronic acid 0.1% of Preparation Example 2
Glucose fructose liquid sugar 12.0%
Acidulant 0.2%
Sweetener 0.1%
Ascorbic acid 0.1%
Grapefruit flavor 0.1%
Remaining amount of purified water ――――――――――――――――――――――――
100%

[Test Example 4]
Using the sodium hyaluronate obtained in Preparation Example 1, a separate liquid seasoning having the following composition was produced. The flavor of the obtained separated liquid seasoning was good.
<Combination ratio>
Sodium hyaluronate of Preparation Example 0.5%
Salad oil 35%
Vinegar (acidity 4%) 22%
Lemon juice 10%
Glucose fructose liquid sugar 5%
3% salt
2% sugar
Sodium glutamate 0.2%
Spice 0.1%
Xanthan gum 0.05%
Shimizu remaining amount ――――――――――――――――――――――――
100%

[Test Example 6]
Using the hyaluronic acid obtained in Preparation Example 2, soft capsules having the following composition were produced.
<Combination ratio>
Hyaluronic acid 20% of Preparation Example 2
50% olive oil
Beeswax 10%
Medium chain fatty acid triglyceride 10%
Emulsifier 10%
――――――――――――――――――――――――
100%

[Test Example 6]
Using the sodium hyaluronate obtained in Preparation Example 1, a powder (granule) having the following composition was produced.
<Combination ratio>
Sodium hyaluronate of Preparation Example 10 10%
Lactose 60%
Corn starch 25%
Hypromellose 5%
――――――――――――――――――――――――
100%

[Test Example 7]
Using the hyaluronic acid obtained in Preparation Example 2, tablets having the following composition were produced.
<Combination ratio>
Hyaluronic acid 15% of Preparation Example 2
Hyaluronic acid (Molecular weight 1 million) 10%
Lactose 24%
20% crystalline cellulose
Corn starch 15%
Dextrin 10%
Emulsifier 5%
Silicon dioxide 1%
――――――――――――――――――――――――
100%

FIG. 1 shows a chromatogram of sodium hyaluronate obtained in Preparation Example 1.

Claims (9)

Hyaluronic acid and / or a salt thereof having an average molecular weight of 1,000 or more and less than 5,000. The hyaluronic acid and / or the molecular weight distribution according to claim 1, wherein the proportion of components having a molecular weight of 1,000 or more is 40% by mass or more and the proportion of components having a molecular weight of 5,000 or more is 40% by mass or less. Its salt. The hyaluronic acid and / or salt thereof according to claim 1 or 2, wherein the proportion of components having a molecular weight distribution of less than 1,000 is 20% by mass or more. The absorbance (A ₆₆₀ ) of the liquid obtained by adding 0.5 g / mL aqueous solution of cetylpyridinium chloride (0.05 g) to 0.1 g / mL aqueous solution (10 mL) of the hyaluronic acid and / or salt thereof. The hyaluronic acid and / or salt thereof according to any one of claims 1 to 3, which is 0.1 Abs or less. The hyaluronic acid and / or salt thereof according to any one of claims 1 to 4, which is obtained by hydrolyzing hyaluronic acid and / or a salt thereof in an acidic aqueous solution. A food composition containing the hyaluronic acid and / or salt thereof according to any one of claims 1 to 5. An oral pharmaceutical composition containing the hyaluronic acid and / or salt thereof according to any one of claims 1 to 5. An oral skin improvement agent comprising the hyaluronic acid and / or salt thereof according to any one of claims 1 to 5 as an active ingredient. An oral skin water content increasing agent comprising the hyaluronic acid and / or salt thereof according to any one of claims 1 to 5 as an active ingredient.