JPS63156707A - Cosmetic containing hyaluronic acid - Google Patents

Abstract

PURPOSE:To obtain a cosmetic having high moisture-retaining property and excellent applicability such as spreadability on the skin, moistness, smoothness (softness) to the skin, etc., and useful as cream, milky lotion, face lotion, pack, etc., by using hyaluronic acids having a specific molecular weight as a component. CONSTITUTION:Hyaluronic acid or its salt having a molecular weight of >=2,000,000 is used as a component of the objective cosmetic. Hyaluronic acid can be separated from a cultured product produced by culturing a microbial strain belonging to Streptococcus zooepidemicus [e.g. Streptococcus zooepidemicus YIT203 (FERM P-8746)] under aerobic condition preferably at 25-38 deg.C. The amount of the hyaluronic acids in the cosmetic is preferably 0.05-2.0wt%. the cosmetic may be properly incorporated with various lubricant, surfactant, preservative, viscosity modifier, drug-active component, perfumery, alcohol, water, etc., and used in the form of face lotion, hair rinse, hair treatment, shampoo, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a cosmetic that has a high moisturizing effect and is comfortable to use.

[Conventional technology]

Among the properties that cosmetics should have, moisturizing properties are particularly important because they prevent irritation from the outside world and skin roughness when cosmetics are applied to the skin, and improve the feeling of use. Conventionally, various studies have been made to impart moisturizing properties to cosmetics. For example, in cosmetics? Contains moisturizing (water retaining) agents such as diols, skin ingredients, and biopolymers.

Skin components, especially hyaluronic acid □, are said to be involved in retaining moisture in human skin, and have recently been incorporated into cosmetics to exhibit excellent moisturizing effects [Fragrance Sharnal Tomb 79.64~ p. 71 (1986): l.

[Problem that the invention seeks to solve]

However, the hyaluronic acid conventionally blended into cosmetics has a molecular weight of about 300,000 to 1,500,000, and its moisturizing effect has not yet been satisfactory.

[Means for solving problems]

Therefore, the present inventors searched for a substance with an even better moisturizing effect, and found that hyaluronic acid with a molecular weight of over 2 million, for which the present applicant had previously applied for a patent (Japanese Patent Application No. 61-99446), The present invention was completed based on the discovery that it has a moisturizing effect superior to that of hyaluronic acid, and that by blending it, a cosmetic with excellent moisturizing effect and feel on use can be obtained.

That is, the present invention provides a cosmetic material containing hyaluronic acid or a salt thereof having a molecular weight of 2 million or more.

The hyaluronic acid used in the present invention has a molecular weight of 2
The production method is not particularly limited as long as the molecular weight is 2,000,000 or more, but for example, a microorganism that produces hyaluronic acid with a molecular weight of 2,000,000 or more is cultured in a nutrient medium by the method described in Japanese Patent Application No. 61-99446. Manufactured by extracting from something.

In the above method, microorganisms that produce hyaluronic acid with a molecular weight of 2 million or more include bacteria belonging to the genus Strezotococcus that have the ability to produce hyaluronic acid, are non-productive of hyaluronidase, and are non-hemolytic, such as the following: One mutant strain of Streptococcus zooepidemicus obtained in this way is mentioned. First, the nasal mucosa is Streptococcus zooepidemicus, which has a strong ability to produce hyaluronidase (hyaluronic acid degrading enzyme) and belongs to Lancefield serogroup C, which produces hyaluronic acid.・Of Determinative Bacteriorozoes, 8th edition, 197
4) is obtained. This strain is known as pine crenan (Mac).
Lennan.

J,Gen,Microbiol,, 14, 134
142, 1956), when hyaluronic acid is produced well under aerobic conditions and glucose is used as a carbon source, 2 tons can be produced by adding 4 hours of glucose.
/! of hyaluronic acid was produced (the yield of hyaluronic acid based on sugar was 5%). The molecular weight of the hyaluronic acid obtained at this time was 300,000 to 600,000. This strain is extracted using the conventional method (bacteria,
Phage Genetic Testing Method, Protein Nucleic Acid Enzyme Separate Volume, Kyoritsu Publishing 1
972) by ultraviolet rays and chemical agents (N-methyl-N'-
Nitro N-nitrosoguanidine (NTG), ethylmethanesulfonic acid, etc.), the treated bacterial cells were mixed and spread on a blood agar medium, a colony that did not show hemolytic properties was collected, and then this strain After mutating it again, it is spread on a nutrient agar medium containing hyaluronic acid, and a colony that does not degrade hyaluronic acid is collected to obtain a mutant strain of Streptococcus zooepidemicus (see Reference Example 1 below). .

One mutant strain of Streptococcus zooepidemicus thus obtained (hereinafter referred to as the present strain) is Todd Hewitt broth.
This bacterium forms transparent colonies with extremely strong viscosity on an agar medium, is non-hemolytic (β-hemolytic: negative), non-hyaluronidase-producing, belongs to Lancefield serogroup C, and is a streptococcus that belongs to Lancefield serogroup C. The mycological properties of this species are as follows.

(a) Durham staining: positive (b) IO°C growth: negative (e) 45°C growth: negative (d) 0.1% methylene blue resistance: negative (e)
6.5% salt resistance: Negative (f) 40% bile resistance: Negative (X) Bacitracin resistance: Positive (h) pH 9,6 resistance: Negative (i) 60°C, 30 minutes resistance: Negative ( j) Gelatin decomposition property: Negative (6) Starch decomposition property: Positive (1) Sodium hippuric acid decomposition property: Negative (e) Aesculin decomposition property: Weak positive (n) Arginine decomposition property: Positive (0) Sugar fermentation nigercose , galactose, sucrose, lactose, maltose, sorbitol, and salicin, and negative for glycerin, mannitol, trehalose, and arabinose.

Based on the mycological properties of this bacterium, the present inventors named this bacterium Strezotococca zuevidemicus YIT 2030, and submitted it to the National Institute of Microbiological Technology, Agency of Industrial Science and Technology as part of the 87th Microbiological Research Institute.
It was deposited as No. 46.

Next, a method for culturing this bacterium and collecting hyaluronic acid having a molecular weight of 2 million or more from the culture will be described.

The medium for culturing this bacterium to obtain hyaluronic acid preferably contains a carbon source, an organic/inorganic nitrogen source, and other inorganic salts and organic micronutrients as necessary. As the carbon source, those containing sugar such as glucose, galactose, sucrose, lactose, fructose, maltose, sorbitol, and starch hydrolyzate are preferable.
Other examples include organic acids and aliphatic alcohols. As the nitrogen source, common materials, organic or inorganic, may be used, but various meat extracts, amino acid mixtures, peptone, yeast extract, etc. are preferable. Furthermore, sodium, potassium, calcium,
Chlorides, sulfates, phosphates, nitrates, carbonates, vitamins, etc. of magnesium, iron, etc. may be added as necessary.

Aerobic conditions are essential for culturing, and it is preferable to increase the stirring speed as the viscosity of the culture solution increases, but excessive stirring is not preferred. The culture temperature is preferably 25-38°C at which bacterial growth occurs.

Furthermore, during culturing, this bacterium produces lactic acid, which inhibits the growth of the bacterium and the production of hyaluronic acid. Therefore, an alkaline aqueous solution is added to neutralize the lactic acid, and the pH of the culture solution is adjusted to 6-6. It is preferable to adjust it within the range of 8. Examples of the alkaline aqueous solution used at this time include aqueous solutions of sodium hydroxide and potassium hydroxide, and aqueous ammonia.

This bacterium has high molecular weight hyaluronic acid (molecular weight over 2 million)
This strain produces extremely high yields and production rates, and particularly good results are obtained when glucose is used as the carbon source. In other words, adding glucose significantly improves the production rate of the desired hyaluronic acid, and the amount added is 0.5
-6% is preferred.

Since this bacterium is a polymeric substance and does not accumulate substances other than hyaluronic acid in the culture solution, it is easy to separate and purify the hyaluronic acid accumulated in the culture solution after culturing, and it is already known to separate and purify polysaccharides. Just use the law.

An example of a method for separating and purifying hyaluronic acid is shown.

Dilute the culture solution with water to an appropriate viscosity (preferably 100cm thick), and adjust the pH with trichloroacetic acid.
to 4 or less. Next, the bacterial cells are separated and removed by centrifugation or membrane filtration (diameter: 0.2 μm or less).

Next, the low molecular weight substances dissolved in the solution are removed by ultrafiltration.
After removal by dialysis, organic solvent precipitation, adsorption using an ion exchange resin, etc., hyaluronic acid with a molecular weight of 2 million or more can be obtained using methods such as organic solvent precipitation, freeze drying, or spray drying.

Regarding the hyaluronic acid obtained by extraction and purification from the above culture solution in this way, a hyaluronic acid standard (molecular weight approximately 630,000,
As a result of various studies while comparing the product with Sigma (manufactured by Sigma), it was confirmed that this product is hyaluronic acid. Its properties are shown below.

(1) Shows the same mobility as the standard sample in electrophoresis using a cellulose acetate membrane.

(2) Decomposed by actinomycete hyaluronidase (manufactured by Ohno Pharmaceutical Co., Ltd.), and the decomposed products are collected using silica gel thin layer Chromadog 2.
When applied to a feed, two spots appear with the same mobility as the processed standard decomposition product.

(3) Analysis of the chemical composition reveals that N-acetyl-D-glucosamine and D-glucuronic acid are present in a molar ratio of 1:1.

(4) The specific light intensity is [α)B = -69°.

(5) The infrared absorption spectrum measured by the thin film method is the same as that of the standard product as shown in Figure 1.

(6) The 13C-NMR spectrum measured after dissolving in heavy water is the same as the standard as shown in Figure 2.

(7) Molecular weight is determined by viscosity measurement method (T, C, Laurent
et al.

Biochim, Biophys, Acta, 42
, 476-485.

1960), it was 2-3 million.

In the cosmetics of the present invention, the above-mentioned hyaluronic acid or its salt having a molecular weight of 2 million or more is blended in an amount of o, oos to 5.0% by weight (hereinafter simply referred to as "chi"), particularly 0.05 to 2.0%. preferable. Examples of the salts of hyaluronic acid include sodium salts, potassium salts, lithium salts, magnesium salts, calcium salts, lysine salts, ammonium salts, triethanolamine salts, and ZoronoQ nolamine salts.

In addition to the above-mentioned hyaluronic acid, the cosmetics of the present invention may contain various oils, surfactants, preservatives, viscosity modifiers, medicinal agents, other humectants, fragrances, alcohols, water, etc. that are usually incorporated into cosmetics. By blending, for example, various creams, emulsions,
Lotion, NoQ Tsuku, hair rinse, hair treatment,
It can be in the form of shampoo, lipstick, foundation, hair growth agent, etc.

The above-mentioned oils include Liquid IQ Rough-in, Vaseline, IQ
Rough-in wax, squalane, beeswax, higher alcohols, fatty acids, etc.; What about them as surfactants? Lioxyethylene fatty acid ester, oxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, -rioxyethylene hydrogenated castor oil, ? Lyoxyethylene sorbitol fatty acid ester, etc.; As alcohol, ethanol etc.:
As viscosity modifiers, calxoxymethyl cellulose, hydroxyethyl cellulose, ? Rivinyl alcohol, carboxyvinyl polymer, xanthan gum, etc.; wetting agents include sorbitol, glycerin, 1,3-butylene glycol, sodium pyrrolidone carboxylate, sodium lactate, etc. Preservatives include alkyl esters of 9-hydroxybenzoic acid, sodium benzoate, potassium sorbate, and the like; medicinal agents include vitamins, anti-inflammatory agents, bactericidal agents, and the like.

[Action and effect of the invention]

The hyaluronic acid with a molecular weight of 2,000,000 or more that is blended into the cosmetics of the present invention has an extremely superior moisturizing effect compared to the hyaluronic acid with a molecular weight of 1,500,000 or less that is blended in conventional cosmetics. Therefore, the cosmetic composition of the present invention containing this composition has a high moisturizing effect and has an extremely good feel when used, such as spreadability on the skin, firmness and stiffness, and smoothness and flexibility on the skin.

〔Example〕

Next, the present invention will be described in detail with reference to Reference Examples and Examples.

Reference Example 1 Strezotoccoccus Φzoepidemicus, which exhibits β-hemolytic properties, produces hyaluronidase, and produces hyaluronic acid, collected from fishy-smelling mucous membrane, was incubated at 37°C for 10 minutes in Todd-Huyts 0 broth medium (manufactured by Difco). After culturing for an hour, the cells in the logarithmic growth phase were collected by centrifugation, and washed aseptically twice with 0.05M Tris-maleic acid buffer (pH 6.0) while repeating centrifugation at low temperatures. The cells were suspended in the same buffer to a bacterial concentration of 1X108/-, and NTG was added thereto at a concentration of 200 μt/11 tl, followed by shaking at 37° C. for 30 minutes. Subsequently, the microbial cells were incubated at low temperature with 0.05 M) lithium-maleic acid buffer (pH
After washing twice with 6,0), the cells were inoculated into Todd Huyt broth medium and cultured at 37°C for 18 hours. This culture solution was diluted with sterile physiological saline at IX 103/m7! Dilute 0.1 ml of blood (rabbit defibrated blood) to
After plating and culturing in agar (20 m/m), colonies that did not show hemolysis were collected. The acquisition frequency of this mutant strain is approximately 4XI
Next, this non-hemolytic strain was cultured in Todd Huyt broth medium at 37°C in the same manner as above, and the cells in the logarithmic growth phase were collected, and 0.05M) After washing with maleic acid buffer (pH 6,0), NTG 20
The mixture was shaken at 37°C for 20 minutes in the same buffer containing 0 ttt/ml. Subsequently, after washing the bacterial cells at low temperature with the same buffer solution, they were inoculated into an ultrafiltration medium (Todd Huitt broth medium with the polymer fraction removed using Amicon's ultrafiltration membrane YM-10). The cells were then cultured at 37°C for 18 hours. This culture solution was diluted with sterile physiological saline at 1-5X102/-
The O, I- was diluted so that it was applied to the above ultrafiltrated medium agar (high purity agar) containing 0.1% of sodium hyaluronate (molecular weight approximately 630,000, manufactured by Sigma). Cultured in a moisture chamber for 20 to 40 hours at 37°C, the grown bacteria in the colony were collected using the replica method, and a 10% aqueous solution of cetylpyridinium chloride was sprayed onto agar. Hyaluronidase non-producing mutant strain Strezotocochus zooepidemicus YIT 2030 that forms colonies with cloudy surroundings.
obtained.

The method for identifying the above-mentioned hyaluronidase-producing φ non-producing bacteria is the method of Erika Balke et al.
al, , Zbl, Bakt, Hyg, A, 259
, 194-200.1985).

Reference example 2 (patch culture) Glucose 6%? Ripezoton (manufactured by Otama Nutritional Chemicals) 1.
5%, No9 yeast extract (manufactured by Oriental Yeast Industries) 0
．． 5%, potassium phosphate 0.2%, magnesium sulfate heptahydrate 0.1%, calcium chloride o, oos%, ADEKA NOL LG-109 (antifoaming agent manufactured by Kadenka Kogyo) 0.0O1
% of the culture medium (pH 7.0) was placed in a 104 t Schafer Mentor, and after sterilization, 1% of the pre-cultured Strezotococcus epidemicus YIT2030 was inoculated, and the mixture was mixed with a 6N-sodium hydroxide aqueous solution. The culture was cultured with aeration at 37° C. for 39 hours while the culture pH was continuously adjusted to 7.

Glucose was sterilized separately and added all at once at the start of culture. As the culture progresses, hyaluronic acid accumulates, and after 29 hours of culture, the viscosity of the culture solution is 8000 cm? After 39 hours of culture, the culture was terminated when the glucose in the culture solution reached zero.

The harvested culture solution has no fluidity, so it is diluted with water to a viscosity of 100 cm. It was diluted to less than az. Next, the pH of this solution was adjusted to 4 or less with trichloroacetic acid,
Pass through a hollow fiber microfilter module (FW-103 manufactured by Asahi Kasei) to remove bacterial cells and insoluble components, and then pass through a hollow fiber ultrafiltration membrane (I (IF50-43 manufactured by Amicon).
Water was added to the filtered solution to remove low-molecular substances in the solution. This solution was dried by freeze-drying to obtain 6.79 hyaluronic acids per 11 culture solutions. The molecular weight of the obtained hyaluronic acid was approximately 2,160,000 (viscosity measurement method).

Reference Example 3 (Continuous Culture) A medium with the same composition as Reference Example 2 except that the glucose concentration was 25% was placed in an IOA' Schafer Mentor, and after sterilization (glucose was sterilized separately), the pre-cultured streptococcus was cultured. Kotsuka zooepidemicus YIT2030 at 1%
Inoculated and cultured in IJum aqueous solution (6N-hydroxide)
While adjusting H to 7, the culture was carried out with aeration at 37° C. for 15 hours. After that, a medium with the same composition as in Reference Example 2 except that the glucose concentration was changed to 2.0% was used at a dilution rate of 0.3 (hr-1).
Continuous culture with aeration and agitation was carried out at 37° C. and pH 7 for one week while continuously adding water. The culture solution flowing out of the culture tank was collected at regular intervals, and hyaluronic acid (molecular weight approximately 2,160,000 [viscosity measurement method]) was extracted and purified in the same manner as in Reference Example 2. As a result, the yield of hyaluronic acid based on sugar was 15%, and its productivity was 0.9 y/l/hr.
It was possible to obtain 21.6 t/l of hyaluronic acid.

Example 1 A lotion having the composition shown in Table 1 was manufactured, and the moisturizing effect when applied to human skin was measured using the impedance method of Tagami et al.
Gami et al., J. Invest.

Dermatol, 75, 500-507, 19
Measuring method of skin surface permittivity improved from 80) (Karl M
o5ler.

5onderdruck aus Parfiimer
ie and Kosmetik64.375~379
．． 1983) was applied to the test. In Table y, the low-molecular-weight hyaluronic acid used was chicken comb-derived hyaluronic acid (Teikoku Zoki Seiyaku ■), and the high-molecular-weight hyaluronic acid obtained in Reference Example 2 was used. Moreover, the numerical values in Table 1 indicate weight %.

Margin Test Method After washing the inner side of the upper arm of a healthy male adult (27 years old) with soap, marks 4X4I7y+ were placed on a total of 6 sites, 3 sites on the left and right pots. Approximately 30 minutes later, the skin surface moisture measuring device (5KICO8
3. Amic Group.

The skin surface permittivity of each area before application of lotion was measured three times using a norope (diameter: 16 fl), and the average value was determined. Immediately after that, apply 3 drops of test lotion to each area (16d).
0μ! Apply it and spread it thoroughly with your fingers. After application, the skin surface permittivity of each site was measured three times over time, and each average value was determined. Based on the skin surface permittivity, the above-mentioned literature (Karl Mo
a1er, 5onderdruck aus Parf
ierieund Kosmetik 64 , 375
The skin surface water content was determined by calculation according to the method of 379, 1983), and the value before application of the sample was set to 0, and it was expressed as a change in the skin surface water content. In order to minimize site differences and errors, the lotion application site was changed and the above measurement was repeated 6 times, and the average value was used. The room temperature during the measurement period was 27-29°C, and the relative humidity was 45-70%.

Test results The results obtained are shown in FIGS. 3 to 5. In the figure, the higher the skin surface moisture content, the higher the moisturizing effect. As a result, the lotion of the present invention containing high molecular weight hyaluronic acid had a superior moisturizing effect compared to the comparative product containing low molecular weight hyaluronic acid.

Example 2 A lotion having the composition shown in Table 2 was produced, and its moisturizing effect when applied to human skin was tested by measuring the skin surface water content. The skin surface moisture content was calculated from the skin surface dielectric constant measured in the same manner as in Example 1, and was expressed as the increase in skin surface moisture, with the value before sample application being set to 0.

The results are shown in Figure 6. The relative humidity at the time of measurement was 44±
2%, and the room temperature was 26±1°C.

In Table 1, the low molecular weight hyaluronic acid with a molecular weight of about 780,000 (manufactured by Teikoku Zoki Seiyaku ■) was used, and the high molecular weight hyaluronic acid produced according to Reference Example 2 was used. The numbers in the table indicate weight factors.

Bottom margin As a result, all of the lotions of the present invention exhibited superior moisturizing effects compared to lotions containing low-molecular-weight hyaluronic acid.

Example 3 A lotion having the composition shown in Table 3 was produced, and its feeling of use was evaluated. Note that the numerical values in Table 3 indicate weight %.

Evaluation method and results: 10 people (5 men and 5 men and women) each applied a certain amount of the lotion shown in Table 3 to the backs of their 79nella hands, and they were asked to apply a certain amount of the lotion shown in Table 3 to the backs of their hands, and they were asked to apply a certain amount of the lotion shown in Table 3 to the backs of their hands, and they were asked to apply a certain amount of the lotion in Table 3 to the backs of their hands. , We asked them to evaluate their sense of comfort using a questionnaire.

As a result, product 8 of the present invention exhibited a significantly superior feeling of use compared to comparative amounts 5 and 6.

In addition, product 7 of the present invention exhibited a significantly superior feeling in use compared to comparison amount 5, and exhibited a feeling in use equivalent to comparison amount 6. Therefore, the high-molecular-weight hyaluronic acid, which is a component of the present invention, exhibits the same effect as that of conventional low-molecular-weight hyaluronic acid at one-fourth the amount.

Example 4 A lotion having the following composition was produced, and its feeling of use was evaluated.

Composition: Ethanol 8.0 Q-poor bene 0.2 1.3-butylene glycol 10.0 Purified water
81.6 Evaluation method and results: Low molecular weight hyaluronic acid (molecular weight approximately 780,000, manufactured by Teikoku Zoki Pharmaceutical Co., Ltd.) was used instead of the above-mentioned lotion of the present invention and high molecular weight hyaluronic acid.
A lotion containing the same amount of
I had them use it for 3 days each. The product was then evaluated using a questionnaire on four items: spreadability on the skin, stickiness, smoothness on the skin, and stiffness.

As a result, the lotion of the present invention was superior to lotions containing low-molecular-weight hyaluronic acid, especially in terms of spreading on the skin, firmness, and stinging sensation.

Example 5 A milky lotion having the following composition was produced and its feeling in use was evaluated.

Composition Nistearic acid 2.5 (wt%) beef
Fat 1.5 fluid Q rough-in 6.0 fluid Q laben
0.3 Monostearate Lupitan 1
．． 51.3-Butylene glycol 6.0 Purified water 79.5 Evaluation method and results: As a result of evaluation using the same method as in Example 4, it was found that the emulsion of the present invention was particularly superior to the emulsion containing low-molecular-weight hyaluronic acid. It had excellent spreadability on the skin, firmness and firmness.

Example 6 A cream having the following composition was manufactured and its feeling on use was evaluated.

Composition: Fluid Q Laugh-in 23.0 (wt%) Octyldodecyl myristate 5.0 Vaseline 6.0 mi
Tsurou
5.0 Stearic acid 2hO Behenyl alcohol 1.0 Sorbitan monostearate 3.01.3-
Butylene glycol 3.0 no Q La Pen 0.3 essence
48.5 Evaluation method and results: As a result of evaluation using the same method as in Example 4, the cream of the present invention had a higher
In particular, it did not have a sticky feeling and was excellent in smoothness and firmness on the skin.

Example 7 A lotion with the following composition was produced.

Composition: ■Ethanol 10.0 (wt%)■
1,3-butylene glycol 2.0■Methylno Q2 pen 0.1■Fragrance
0.1 ■Purified water A total amount of 100 Production method: ■Dispersed in ■, Added ■, ■, ■, ■, and ■ to this and sufficiently stirred to obtain a lotion.

Example 8 A milky lotion having the following composition was produced.

Composition: ■ Stearic acid 2.0 (wt%) ■ Fluid Q Rough In 6.0 ■ Squalane
2.0 ■ Nlupitan Monostearate 1.5 ■ Zotylno Q Laben 0.05 ■ 1,3-Butylene Glycol 3.0 ■ Methylno 92 Pen
0.1 [phase] fragrance
0.15■ Purified water Amount that makes the total 100 Production method: Add ■ and ■ to ■ and disperse ■ to obtain a dispersion. Next, this was added to ① to ② at 80°C to emulsify, and then [phase] was added and cooled to room temperature to obtain a milky lotion.

Example 9 A cream having the following composition was produced.

Composition: ■Fluid Q rough-in 23.0 (weight) ■Vaseline
7.0 ■ Cetol 1.0 ■ Stearic acid zO ■ Beeswax
2.0 ■ Sorbitan monostearate
3.5 ■ Butyl, Q Laben 0.05 [Phase] 1,3-butylene glycol 3.0 ■ Methyl Q Laben 0.1 @Fragrance
0.15◎Purified water
Production method for a total amount of 100: Add [phase] and ■ to [phase], and disperse ■ into this to obtain a dispersion. Next, this was added to ① to ① at 80°C to emulsify it, and then @ was added and cooled to room temperature to obtain cream.

Example 10 A hair growth agent having the following composition was produced.

Margin below Example 11 A hair rinse having the following composition was manufactured.

41-1 Example 12 A shampoo having the following composition was manufactured.

421 Example 13 A foundation having the following composition was manufactured.

[Brief explanation of the drawing]

FIG. 1 and FIG. 2 are drawings showing the infrared absorption spectrum and NMR spectrum of the polymeric hyaluronic acid obtained in Reference Example 2, respectively. 3 to 5 are drawings showing the relationship between changes in skin surface moisture content and time after application when the lotion of Example 1 is applied. FIG. 6 is a drawing showing the relationship between the change in skin surface moisture content and the time after application when the lotion of Example 2 is applied. Figure 3: Time after application (minutes) Figure 4: Time after application (minutes)

Claims (1)

[Scope of Claims] 1. A cosmetic containing hyaluronic acid or a salt thereof having a molecular weight of 2 million or more. 2. The cosmetic according to claim 1, wherein the hyaluronic acid having a molecular weight of 2 million or more is produced by microorganisms. 3. The cosmetic according to claim 2, wherein the microorganism that produces hyaluronic acid with a molecular weight of 2 million or more is a bacterium belonging to Streptococcus zooepidemicus. 4. The microorganism that produces hyaluronic acid with a molecular weight of over 2 million is Streptococcus zooepidemicus YIT20
30 (Keikoken Bokuyori No. 8746), according to claim 2 or 3.