JP2008056569A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for skin having moisturizing action and cell-activating action and having high permeability. <P>SOLUTION: The external preparation for skin comprises at least arginine, aspartic acid, isoleucine, leucine, lysine, threonine, glycine, histidine, serine, valine, tyrosine, cysteine, phenylalanine, hydroxyproline and acylglutamine or salts thereof among aminoacids. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a skin external preparation that can be applied to various skin external preparations such as pharmaceuticals, quasi drugs, and cosmetics (preparations used for humans and other animals).

The skin is covered with a stratum corneum, which is a thin biological protective film, and it is possible to live in a dry atmosphere without losing moisture, because the stratum corneum exists on the skin in contact with the outside world, that is, the epidermis. It is. The stratum corneum keeps the water from the body from losing, and at the same time, makes various adjustments so that the skin remains normal.
However, the skin is damaged and hardened due to trauma (burn, inflammation caused by various stimulating factors such as ultraviolet rays, etc.), the stratum corneum is cracked and peeled off, and a large amount of water is lost compared to normal skin. Will happen.

  On the other hand, a decrease in skin water content is often caused or involved as one of the causes for losing the flexibility, extensibility and strength necessary for the stratum corneum. A functionally defective stratum corneum does not have enough water binding (retention) force to keep the stratum corneum flexible, and conversely allows a large amount of moisture to pass through and lose skin. In general, when the moisture content decreases to 10% or less of the dry weight of the stratum corneum, it loses the softness and softness of the skin that has been kept until then, becomes hard and brittle, so-called crisp, moist feeling It can be said that the moisture content of the skin stratum corneum is very important because it results in no dry skin (skin).

  Therefore, conventionally, in order to make up for this point, cosmetics have been ideally reproduced on the skin with substances similar to those on the skin surface. Many of them are used. In recent years, a stratum corneum component called NMF (Natural Moisturizing Factor) has attracted attention as a third cosmetic component, and research and development of amino acids and derivatives thereof, which are NMF components, have been actively conducted. (Moisturizing / cleaning / ultraviolet absorption / antibacterial action, etc.).

On the other hand, various cell activators have been proposed in order to keep the skin healthy. For example, it is known that the above-mentioned amino acids have a cell-activating effect, as well as collagen-related amino acid derivatives such as hydroxyproline (Patent Document 1) and various derivatives such as N-acylamino acids (Patent Document 3). Has been.
However, when the additive is, for example, an amino acid, there are many types of amino acids and derivatives thereof, the relationship between the combination of amino acids or amino acid derivatives and their effectiveness on skin cells, and the optimal combination in consideration of penetration into the skin, etc. Was left with challenges.

JP-A 61-289016 JP-A-6-279227 Special table 2002-508308 gazette

As described above, amino acids and their derivatives have been known for various uses in the cosmetics field, but there is still room for improvement with regard to the combination and formulation of amino acids in consideration of skin permeability. It was.
Therefore, we have intensively studied additive substances with regard to formulations useful for pharmaceuticals, quasi-drugs, and cosmetics that have a cell activation effect and excellent moisture retention.
The present invention provides a skin external preparation having a moisturizing action and a cell activation action and having a penetrating feeling.

The objectives of the previous term were achieved by the following 1 to 9.
1. A skin external preparation containing at least arginine, aspartic acid, isoleucine, leucine, lysine, threonine, glycine, histidine, serine, valine, tyrosine, cysteine, phenylalanine, hydroxyproline and acylglutamine, or salts thereof among amino acids. .
2. Regarding the addition amount of amino acids or salts thereof, the addition amount of arginine is 20 to 400 microweight percent, the addition amount of aspartic acid is 3 to 60 microweight percent, the addition amount of isoleucine is 30 to 600 microweight percent, leucine 30-600 micro weight percent, lysine added 30-600 micro weight percent, threonine added 25-500 micro weight percent, glycine added 6-120 micro weight percent, histidine added The amount is 8 to 160 micro weight percent, the amount of serine is 8 to 160 micro weight percent, the amount of valine is 30 to 500 micro weight percent, the amount of tyrosine is 0.08 to 20 micro weight percent, the amount of cysteine is 15-300 microweight percent, phenylalanine addition amount is 0.12-20 microweight percent -The skin external preparation of 1. whose addition amount of 5-cent, hydroxyproline is 5-150 microweight percent.

3. The topical skin preparation according to 1., wherein the acylglutamine is acetylglutamine.
4. The external preparation for skin according to 3, wherein the addition amount of acetylglutamine is 10 to 800 micro weight percent.
5. A skin external preparation according to 1. to 3. containing vitamin B.
6. The topical skin preparation of 5. wherein vitamin B is vitamin B1 or vitamin B6.
7. An external preparation for skin according to 1. to 6, containing hyaluronic acid or a salt thereof.
8. The external preparation for skin according to 1. to 7, wherein the external preparation for skin is cosmetic or quasi-drug.
9. The external skin preparation according to 8., wherein the external skin preparation is a lotion, an emulsion, a cream, a hair nourishing agent, or a pack.

  According to the present invention, it is possible to provide an external preparation having a moisturizing action and a cell activating action and having a penetrating feeling.

The amino acids used as essential in the present invention are arginine, aspartic acid, isoleucine, leucine, lysine, threonine, glycine, histidine, serine, valine, tyrosine, cysteine, phenylalanine, or salts thereof. They may be optically active or racemic, but all of them are particularly preferred.
The amount of amino acids added as essential in the present invention will be described in detail.
The amount of arginine added is preferably 20 to 400 microweight percent, more preferably 40 to 200 microweight percent, and most preferably 60 to 120 microweight percent.
The amount of aspartic acid added is preferably 3 to 60 micro weight percent, more preferably 8 to 30 micro weight percent, and most preferably 12 to 20 micro weight percent.
The amount of isoleucine added is preferably 30 to 600 microweight percent, more preferably 50 to 300 microweight percent, and most preferably 80 to 200 microweight percent.
The amount of leucine added is preferably 30 to 600 microweight percent, more preferably 50 to 300 microweight percent, and most preferably 80 to 200 microweight percent.

The amount of lysine added is preferably 30 to 600 microweight percent, more preferably 50 to 300 microweight percent, and most preferably 80 to 200 microweight percent.
The amount of threonine added is preferably 25 to 250 micro weight percent, more preferably 40 to 150 micro weight percent, and most preferably 60 to 120 micro weight percent.
The amount of glycine added is preferably 6 to 120 microweight percent, more preferably 16 to 60 microweight percent, and most preferably 20 to 40 microweight percent.
The amount of histidine added is preferably 8 to 160 micro weight percent, more preferably 20 to 90 micro weight percent, and most preferably 30 to 60 micro weight percent.
The amount of serine added is preferably 8 to 160 micro weight percent, more preferably 20 to 90 micro weight percent, and most preferably 30 to 60 micro weight percent.

The amount of valine added is preferably 30 to 500 micro weight percent, more preferably 50 to 200 micro weight percent, and most preferably 70 to 150 micro weight percent.
The amount of tyrosine added is preferably 0.08 to 20 micro weight percent, more preferably 0.15 to 15 micro weight percent, and most preferably 0.3 to 12 micro weight percent.
The amount of cysteine added is preferably 15 to 300 micro weight percent, more preferably 30 to 150 micro weight percent, and most preferably 40 to 80 micro weight percent.
The amount of phenylalanine added is preferably 0.12 to 20 microweight percent, more preferably 0.15 to 10 microweight percent, and most preferably 0.3 to 1 microweight percent.

Next, hydroxyproline used in the present invention will be described.
Hydroxyproline may be optically active or racemic, but L form is particularly preferred. The hydroxy group may be cis or trans. The amount of hydroxyproline added is preferably 5 to 150 microweight percent, more preferably 10 to 90 microweight percent, and most preferably 15 to 60 microweight percent.
The acyl glutamine used in the present invention may be an optically active substance or a racemate, but the L form is particularly preferred. The acyl group is preferably an acyl group having 2 to 8 carbon atoms, more preferably an acyl group having 2 to 6 carbon atoms, and most preferably an acetyl group having 2 carbon atoms. The acyl glutamine is not particularly limited, but acetyl glutamine is preferable. The amount of acylglutamine added is preferably 10 to 800 microweight percent, more preferably 20 to 400 microweight percent, and most preferably 40 to 200 microweight percent.

Vitamins have been used for various skin external preparations due to their coenzyme activity, but vitamins belonging to the vitamin B group are particularly preferred when combined with the composition of the present invention. Vitamin Bs used in the present invention are specifically vitamin B1, vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin B6, vitamin B12, vitamin B13, vitamin B15, vitamin B17, vitamin BT, vitamin Bx, vitamin Bc, vitamin B1 involved in sugar metabolism, vitamin B2 involved in lipid metabolism, and vitamin B6 involved in protein metabolism are preferred, and vitamin B1 and vitamin B6 are more preferred.
The amount of vitamin B used in the present invention is preferably 0.8 to 16 micro weight percent, more preferably 2 to 9 micro weight percent, and most preferably 3 to 6 micro weight percent.

  In the present invention, it is particularly preferable to add hyaluronic acid in order to maintain skin elasticity. The hyaluronic acid may be a sodium salt or a potassium salt, or may be a free acid. When the skin external preparation of the present invention is a cosmetic, addition of hyaluronic acid is particularly preferable. The amount of hyaluronic acid used in the external preparation for skin is preferably 150 to 3000 micro weight percent, more preferably 300 to 1500 micro weight percent, and most preferably 400 to 800 micro weight percent.

The skin external preparation of the present invention can be used in combination with various medicinal agents. Such medicinal agents are, for example, active oxygen scavengers, antioxidants, cell activators, anti-inflammatory agents, tyrosinase activity inhibitors, UV absorbers and humectants. Specific examples of the medicinal agent include those shown below, but of course not limited thereto.
The active oxygen scavenger or antioxidant that can be used in the present invention is not particularly limited, but is preferably extracted or purified from natural products rather than those obtained by chemical synthesis.

  Examples of the active oxygen scavenger include β-carotene, α-carotene, lycopene, lutein, astaxanthin, capsanthin, fucoxanthin, heteroxanthine, loroxanthin, luteoxanthine, lycophy, lycoxanthin, neochrome, neoxanthine, rhodopine, rhodopinal. , Rhodopinol, rhodovibrin, trolixanthine, xanthophyll, zeaxanthin and other carotenoids, superoxide dismutase, mannitol, rutin and derivatives thereof, bilirubin, cholesterol, tryptophan, histidine, quercetin, quercitrin, catechin, catechin derivatives, gallic acid and derivatives thereof , Glutathione and its derivatives, and salts thereof, hornon extract, ginkgo biloba extract, keiketto extract, hawthorn extract , Plant extracts containing flavonoids, such as Mikaika extract, Yukinosita extract, Melissa extract, Gennoshoco extract, button pi extract, parsley extract, tormentilla extract, Rakan fruit extract, Yashajitsu extract and Zicopi extract Can be mentioned.

  Antioxidants include, for example, retinol and its derivatives such as retinol palmitate and retinol acetate, retinal and its derivatives, vitamin A such as dehydroretinal; thiamines such as thiamine hydrochloride and thiamine sulfate, riboflavin, pyridoxine hydrochloride , Pyridoxines such as pyridoxine dioctanoate, flavin adenine nucleotide, cyanocobalamin, folic acid, nicotinic acid amide, nicotinic acid such as benzyl nicotinate, calcium pantothenate, D-pantothenyl alcohol, pantothenyl ethyl ether, acetyl pantothenyl Pantothenic acids such as ethyl ether, vitamin B such as choline and inositol; L-ascorbic acid, L-ascorbyl palmitate, L-ascorbyl dipalmitate, isopalmitic acid L Ascorbyl, L-ascorbyl diisopalmitate, L-ascorbyl tetraisopalmitate, L-ascorbyl stearate, L-ascorbyl distearate, L-ascorbyl isostearate, L-ascorbyl diisostearate, L-ascorbyl myristate, dimyristin L-ascorbyl acid, L-ascorbyl isomyristate, L-ascorbyl diisomyristate, L-ascorbyl oleate, L-ascorbyl dioleate, L-ascorbyl 2-ethylhexanoate, sodium L-ascorbate phosphate, L-ascorbic acid phosphate potassium, L-ascorbic acid phosphate magnesium, L-ascorbic acid phosphate calcium, L-ascorbic acid phosphate aluminum , Sodium L-ascorbate sulfate, potassium L-ascorbate sulfate, magnesium L-ascorbate sulfate, calcium L-ascorbate sulfate, aluminum L-ascorbate sulfate, sodium L-ascorbate, L- Vitamin C such as ascorbic acid and its derivatives such as potassium ascorbate, magnesium L-ascorbate, calcium L-ascorbate, aluminum L-ascorbate, and their salts; ergocalciferol, cholecalciferol, dihydroxystanal, etc. Dl-α (β, γ) -tocopherol, dl-α-tocopherol acetate, nicotinic acid-dl-α-tocopherol, linoleic acid-dl-α-tocopherol, succinic acid d Examples include tocopherols such as l-α-tocopherol and derivatives thereof, salts thereof, vitamin E such as ubiquinones, dibutylhydroxytoluene and butylhydroxyanisole.

  Among the above active oxygen scavengers and antioxidants, preferred are mannitol, beta carotene, astaxanthin, rutin and derivatives thereof, ginkgo biloba extract, oxon extract, keiketou extract, saxifrage extract, melissa extract, gennoshoco Extracts, Ages extract, vitamins C and their derivatives and salts thereof, vitamin E and its derivatives and salts thereof, and more preferable are beta carotene, astaxanthin, ginkgo extract, vitamins C and Their derivatives and their salts, vitamin E and its derivatives and their salts.

  The concentration of the active oxygen removing agent or antioxidant in the external preparation for skin of the present invention is preferably 0.00001 to 50% by weight, more preferably 0.0001 to 30% by weight. However, when using a plant extract, there is no problem as long as the dry solid content is within the above range. Further, the active oxygen scavenger or the antioxidant can be used alone or in combination of two or more.

(Cell activator)
Examples of the cell activator include adenylate derivatives such as deoxyribonucleic acid and salts thereof, adenosine triphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, guanine, xanthine and derivatives thereof and salts thereof. Nucleic acid-related substances such as serum deproteinized extract, spleen extract, placenta extract, chicken crown extract, royal jelly extract, etc .; yeast extract, lactic acid fermentation extract, bifidobacteria extract, ganoderma extract Extracts derived from microorganisms such as foods; extracts derived from plants such as carrot extract, assembly extract, rosemary extract, agaric extract, garlic extract, hinokitiol, cephalanthin; α- or γ-linolenic acid, Eicosapentaenoic acid and their derivatives, succinic acid and its derivatives and their salts, estradiol and its derivatives And α-hydroxy acids such as lactic acid, glycolic acid, citric acid, malic acid, salicylic acid, and derivatives thereof, and salts thereof.

Among these cell activators, particularly preferred are deoxyribonucleic acid and its salt, adenosine triphosphate and its salt, serum deproteinized extract, placental extract, yeast extract, lactic acid fermentation extract, carrot extract, Hinokitiol, succinic acid and its derivatives and their salts.
The concentration of the cell activator in the external preparation for skin of the present invention is preferably 0.0001 to 5% by weight, more preferably 0.001 to 3% by weight. However, when using a plant extract, there is no problem as long as the dry solid content is within the above range. Moreover, a cell activator can be used 1 type or in combination of 2 or more types.

(Anti-inflammatory agent)
Anti-inflammatory agents include glycyrrhizic acid, glycyrrhetinic acid, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene and their derivatives and their salts, ε-aminocaproic acid, zinc oxide, diclofenac sodium, aloe extraction Products, salvia extract, arnica extract, chamomile extract, birch extract, hypericum extract, eucalyptus extract, mukuroji extract and the like.
Among these anti-inflammatory agents, particularly preferred are glycyrrhizic acid, glycyrrhetinic acid, guaiazulene and derivatives thereof, and salts thereof, ε-aminocaproic acid, aloe extract, chamomile extract.
The concentration of the anti-inflammatory agent is generally 0.0001 to 1%, preferably 0.01 to 0.5% in the composition. However, when using a plant extract, there is no problem as long as the dry solid content is within the above range. The anti-inflammatory agents can be used alone or in combination of two or more.

(Tyrosinase activity inhibitor)
Examples of tyrosinase activity inhibitors include cysteine and derivatives thereof (for example, N, N′-diacetylcystine dimethyl, etc.) and salts thereof, Sempukuka extract, quette extract, sunpens extract, Sohakuhi extract, Toki extract, Ibukitorano extract Products, Clara extract, hawthorn extract, white lily extract, hop extract, Neubara extract, Yokuinin extract and the like.
The concentration of the tyrosinase activity inhibitor is preferably 0.0001 to 2%, particularly preferably 0.001 to 0.5%. However, when using a plant extract, there is no problem as long as the dry solid content is within the above range. In addition, these can be used 1 type or in combination of 2 or more types.

(Humectant)
As the humectant, not only synthetic compounds such as urea, but also low molecular weight compounds such as amino acids known as natural moisturizing factors, pyrrolidone carboxylic acid and lactate can be used. In addition, mucopolysaccharides and / or proteins that are constituents of the skin and are conventionally blended in cosmetics can be used.

Among these, amino acids include those described in “Development of Newly Useful Cosmetics”, Masato Suzuki / Supervision, CMC Publishing, September 2004, pages 16-19.
Examples of the mucopolysaccharide include hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin and keratan sulfate, and salts thereof. Hyaluronic acid, chondroitin sulfate, and salts thereof can be preferably used. .
Examples of the protein include collagen, elastin, keratin and derivatives thereof, and salts thereof, and collagen is particularly preferable. There is no restriction | limiting in particular about the origin of each of these components, Any of animal origin, microorganism origin, and a synthetic product may be sufficient. There are no particular restrictions on the extraction method and the purification treatment method in the case of natural origin.
These moisturizing components may be of one type, or two or more types can be added and used as appropriate.
Furthermore, the amount of the moisturizing agent varies depending on the combination of the components, but is generally preferably 0.0001 to 5%, more preferably 0.001 to 3%.

  The amino acid, vitamin B and xylitol compositions comprising the amino acids of the present invention or salts thereof can be prepared by blending with various forms of bases known as ordinary external compositions according to conventional methods. That is, oil agents (natural animal and vegetable oils, semi-synthetic oils and fats, hydrocarbon oils, higher fatty acids, ester oils, silicone oils, fluorine-based oil agents, etc.), gelling agents, metal soaps, surfactants (anionic, cationic, amphoteric, Powders (inorganic powders, organic powders, pigments, etc.), alcohols (higher alcohols, polyhydric alcohols, sterols, etc.), water-soluble polymers (animal and vegetable systems, microbial systems, synthetic systems), film forming agents, resins, Preservatives, antibacterial agents, fragrances, essential oils, salts, water (purified water, hot spring water and deep water), pH adjusters, refreshing agents, skin roughness improvers, blood circulation promoters, skin astringents, antiseborrheic agents, amino acids , Nucleic acid-related substances, enzymes, hormones, inclusion compounds, plant extracts, animal and microbial extracts, UV scattering agents and the like can be added.

  Hereinafter, the present invention will be described in detail based on examples, but it goes without saying that the present invention is not limited thereto.

Effect of amino acid content in medium on proliferation of epidermal keratinocytes a) Culture of human epidermal keratinocytes Human normal epidermal keratinocytes (Sanko Junyaku) were used as cells. The medium is a growth factor of 50 mg / l BPE (bovine pituitary extract, chondin bio), 5 mg / l insulin (SIGMA), 0.1 mM ethanolamine (SIGMA), 0.1 mM phosphoethanolamine (SIGMA), 0 MCDB153 medium (Kohjin Bio) supplemented with 0.0001 mg EGF (epidermal growth factor, SIGMA) was used. Pre-cultured to a semi-confluent state at 37 ° C. in a 5% (v / v) CO ₂ atmosphere.
b) Preparation of human epidermal keratinocytes Keratinocytes cultured in a proliferative state in T75 flasks were used. After removing the medium by suction, 5 ml of 0.25% trypsin solution was added and incubated at room temperature for 10 minutes. 10 ml of medium was added thereto, and the cells were peeled and collected by pipetting. The obtained cell suspension was centrifuged at 1000 rpm for 5 minutes, and the supernatant was removed. The obtained cell pellet was suspended in 10 ml of medium, centrifuged at 1000 rpm for 5 minutes, and the supernatant was removed. Again, the obtained cell pellet was suspended in 10 ml of the medium, centrifuged at 1000 rpm for 5 minutes, and the supernatant was removed. The obtained cell pellet was suspended in 2 ml of the medium, and the number of cells was counted.

c) Proliferation of human epidermal keratinocytes for various amino acid concentrations In order to clarify the optimum blending amount of each amino acid, MCDB153 medium in which the concentration of only the target amino acid was changed was prepared. As growth factors, 50 mg / l BPE (bovine pituitary extract), 5 mg / l insulin, 0.1 mM ethanolamine, 0.1 mM phosphoethanolamine, 0.00001 mg EGF (epidermal growth factor was added. 1 ml of this medium. 3 × 10 ⁴ of the above cells were mixed, seeded in a 24-well plate, and the number of cells after culturing at 37 ° C. for 5 days in a 5% (v / v) CO ₂ atmosphere was counted.

Example 1
Effect of amino acids on proliferation of human epidermal keratinocytes
Of 20 amino acids (Wako Pure Chemicals: valine, leucine, isoleucine, alanine, arginine, glutamine, lysine, aspartic acid, glutamic acid, cysteine, threonine, methionine, histidine, phenylalanine, tyrosine, tryptophan, asparagine, glycine, serine) A specific amino acid deficient medium was prepared by reducing only one type to an amount of 10% by weight of the normal MCDB153 medium concentration, and compared with a non-deficient medium. The relative ratio with respect to the case where the number of cells in the non-deficient medium is 100 is shown in Table 1 below.

  From Table 1, the growth of amino acids, arginine, aspartic acid, isoleucine, leucine, lysine, threonine, glycine, histidine, serine, valine, tyrosine, cysteine, phenylalanine deficient medium is particularly suppressed in growth, and the above amino acids are keratinized in the human epidermis. It can be seen that it is particularly necessary for cell growth.

Example 2
Effects of amino acids and additives on the growth of human epidermal keratinocytes
A test medium composition was prepared by adding amino acids to MCDB153 medium such that the amino acid composition was as shown in Tables 2 to 23 below.
The test medium shown in Table 19 has a composition similar to that shown in the known examples of JP-A 61-289016.
The relative ratios with respect to the number of cells in a normal MCDB153 medium with no amino acid added as 100 are shown in Tables 24-27 below.

The composition 2-1 of the present invention promoted the growth of human epidermal keratinocytes, and the effect was enhanced by vitamin B6 and vitamin B1 (composition 2-2 of the present invention). As the amino acid concentration is increased, the accelerating effect is increased, but the accelerating effect is not infinite and almost saturated at the concentration shown in the present invention (the present composition 2-3, 4).
The same concentration dependence was recognized also about each amino acid (invention composition 2-5 to 2-34). Moreover, the growth of human epidermal keratinocytes was suppressed in a medium to which no amino acid of the present invention was added (Comparative compositions 2-1 to 2-15).
Moreover, the growth promotion effect was not recognized by the combination of a known amino acid (Comparative compositions 2-16 to 2-17).

(Cosmetics test)
Reference example 1
A skin care lotion was made with the following composition.
Each component was mixed at 70 ° C. so as to have the concentrations shown in Table 28 below to form an aqueous solution, and then cooled to room temperature.

Reference example 2
A skin care emulsion was prepared with the following composition.
A liquid Each component was mixed at 70 degreeC so that it might become a composition of Table 29, and it was set as the aqueous solution.

B liquid Each component was mixed at 70 degreeC so that it might become the composition ratio of Table 30.

Manufacturing method
65 ml of liquid A and 15 g of liquid B were mixed at 70 ° C., 20 ml of xanthan gum (2% aqueous solution) was added, and the mixture was mixed at 70 ° C. until uniform. Then, it cooled to room temperature.

Reference Example 3
A skin care cream was prototyped with the following composition.
A liquid Each component was mixed at 70 degreeC so that it might become the composition of Table 31, and it was set as the aqueous solution.

B liquid Each component was mixed at 70 degreeC so that it might become the composition ratio of Table 32. FIG.

Manufacturing method
51 ml of liquid A and 40 g of liquid B were mixed at 70 ° C., 1.0 g of triethanolamine was added, and the mixture was mixed at 70 ° C. until uniform emulsification. Then, it cooled to room temperature.

Example 3
Skin Care Lotion Evaluation Method Test Panel 10 healthy women aged 27-35 years, average age 31.6 years Location Room with a temperature of about 24 ° C and humidity of about 55 percent.
Evaluation method It apply | coated to the random position inside the forearm after washing | cleaning, and test | use feeling (sensory feeling) was scored on the basis of the following sensory test results.

4 Feels very well
3 Well felt well
2 I don't feel much
1 I can't feel

Then, the average evaluation score of 10 panelists was obtained and ranked as follows.

A 3.2 or higher
B 2.7 to less than 3.2
C 2.2 to less than 2.7
D 1.7 or more and less than 2.2
E Less than 1.7

Skin Care Lotion The composition shown in Table 28 was used as the present invention, and acetylglutamine was removed as Comparative Example 3-1, and hydroxyproline was removed as Comparative Example 3-2.

  The result of inquiring about the impression after about 5 minutes after applying the coating thoroughly is shown below.

  As is apparent from the table, the lotion of the present invention using a specific amino acid together with acetylglutamine and hydroxyproline has a strong penetrating feeling, is excellent in moist feeling and elongation, and is a comprehensive cosmetic product.

Example 4 (moisturizing effect)
The evaluation panel is the same as before, with an average age of 33.8 years.
The moisturizing effect was evaluated by measuring the amount of horny moisture by the high frequency impedance method.
(Asahi BioMed's high-sensitivity horny layer moisture meter ASA-MX, double frequency phase difference amplitude detection method)
Skin Care Emulsion The composition shown in Table 29 was used as the present invention, and acetylglutamine was removed as Comparative Example 4-1, and hydroxyproline was removed as Comparative Example 4-2.

  After the application was applied thoroughly, the skin conductivity was measured about 18 hours later, and the increase rate after application was determined.

  As apparent from the table, the composition of the present invention showed excellent moisture retention.

Example 5
Evaluation method The evaluation panel is the same as before, with an average age of 332.4 years.
Each day, twice in the morning and noon, after washing both hands, it was applied to the back of the hand and used for 2 weeks.
The test results were scored according to the following criteria.
Skin activation effect

4 I feel a lot of improvement in skin tension and gloss
3 Well felt
2 I don't feel much
1 I can't feel

Then, the average evaluation score of 10 panelists was obtained and ranked as follows.

A 3.2 or higher
B 2.7 to less than 3.2
C 2.2 to less than 2.7
D 1.7 or more and less than 2.2
E Less than 1.7

Rough skin suppression effect

4 I feel the improvement of rough skin and rough skin
3 Well felt
2 I don't feel much
1 I can't feel

Then, the average evaluation score of 10 panelists was obtained and ranked as follows.

A 3.2 or higher
B 2.7 to less than 3.2
C 2.2 to 2.7
D 1.7 or more and less than 2.2
E Less than 1.7

  The composition shown in Table 31 was defined as the present invention, except that acetylglutamine was excluded and comparative example 5-1 was obtained, and hydroxyproline was excluded as comparative example 5-2.

  As apparent from Table 38, the composition of the present invention showed excellent skin activation and rough skin suppression effect.

Claims (9)

  A skin external preparation containing at least arginine, aspartic acid, isoleucine, leucine, lysine, threonine, glycine, histidine, serine, valine, tyrosine, cysteine, phenylalanine, hydroxyproline and acylglutamine, or salts thereof among amino acids.   Regarding the addition amount of amino acids or their salts, the addition amount of arginine is 20 to 400 microweight percent, the addition amount of aspartic acid is 3 to 60 microweight percent, the addition amount of isoleucine is 30 to 600 microweight percent, the addition of leucine 30-600 micro weight percent, lysine added 30-600 micro weight percent, threonine added 25-500 micro weight percent, glycine added 6-120 micro weight percent, histidine added 8 to 160 micro weight percent, serine addition amount is 8 to 160 micro weight percent, valine addition amount is 30 to 500 micro weight percent, tyrosine addition amount is 0.08 to 20 micro weight percent, cysteine addition amount is 15 to 300 micro weight percent, phenylalanine added from 0.12 to 20 micro weight St, skin external preparation according to claim 1, wherein the amount added is 5 to 150 micro-% by weight of hydroxyproline.   2. The skin external preparation according to claim 1, wherein the acyl glutamine is acetyl glutamine.   4. The skin external preparation according to claim 3, wherein the addition amount of acetylglutamine is 10 to 800 microweights percent.   The skin external preparation in any one of Claims 1-4 containing vitamin B.   The topical skin preparation according to claim 5, wherein the vitamin B is vitamin B1 or vitamin B6.   The skin external preparation in any one of Claims 1-6 containing a hyaluronic acid or its salt.   The skin external preparation according to any one of claims 1 to 7, wherein the skin external preparation is a cosmetic or a quasi-drug.   The skin external preparation according to claim 8, wherein the skin external preparation is a lotion, an emulsion, a cream, a hair nourishing agent, or a pack.