JPH08325131A - Cosmetic - Google Patents

Abstract

PURPOSE: To obtain a cosmetic having excellent dampness-keeping property, good fitting to skin and excellent use feeling. CONSTITUTION: This cosmetic contains more than one compounds selected from alanylglutamine, N-acylalanylglutamine of formula I (R<1> is H or a lower alkyl), prolylphenylalanine, N-acylprolylphenylalanine of formula II and their salts. A dipeptide selected from alanylglutamine and prolylphenylalanine, and N-acyldipeptide selected from the formula I and the formula II are blended into the objective cosmetic in the amounts of respectively 0.01-10wt.% and 0.05-2wt.% to whole of the cosmetic. The cosmetic is preparable to a fundamental cosmetic of solubilized system, emulsified system, dispersion system and powdery system, a makeup cosmetic and a hair cosmetic, etc.

Description

Detailed Description of the Invention

[0001]

The present invention relates to alanylglutamine,
The present invention relates to a cosmetic composition comprising one or more compounds selected from N-acylalanylglutamine, prolylphenylalanine, N-acylprolylphenylalanine and salts thereof.

[0002]

2. Description of the Related Art The amount of natural moisturizing factors such as collagen contained in the skin decreases due to external factors such as ultraviolet rays or dryness or physical factors such as aging. When the amount of natural moisturizing factor decreases, the skin becomes dry, and when it deteriorates, it becomes a rough skin condition. For the purpose of preventing the skin from drying, a cosmetic may contain a moisturizing component for keeping the skin moist.
As the moisturizing component, an amino acid or its derivative, which is a main component of natural moisturizing factor and is less irritating to the skin, is used.

However, when an amino acid or a derivative thereof is used as a moisturizing component, there are problems that the feeling of use is heavy and that it does not fit into the skin. Alanylglutamine is used as a bulk powder for infusion (JP-A-6-234715) or a hair growth-promoting agent (JP-A-6-32726), and prolylphenylalanine is a hypotensive agent (JP-A-3-133391).
No.) and N-acetylalanylglutamine as nutritional compositions (JP-A-4-305596), but their use as cosmetics is not known.

Regarding the use of dipeptides as cosmetics, it is known that glycylglycine imparts a buffering ability to cosmetics (Japanese Patent Publication No. 55-16125).

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a cosmetic composition which has excellent moisturizing properties, is well adapted to the skin, and has an excellent feeling in use.

[0006]

According to the present invention, alanylglutamine, a compound of general formula (I)

[0007]

Embedded image

N-acylalanylglutamine represented by the formula (wherein R ¹ represents a hydrogen atom or lower alkyl) [hereinafter referred to as compound (I)], prolylphenylalanine, general formula (II)

[0009]

[Chemical 4]

One or more compounds selected from N-acylprolylphenylalanine represented by the formula (wherein R ² represents a hydrogen atom or lower alkyl) [hereinafter referred to as compound (II)] and salts thereof are blended. The cosmetics can be provided. The present invention will be described in detail below.
In the definitions of the compound (I) and the compound (II), the lower alkyl is linear or branched and has 1 to 6 carbon atoms.
, Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl and the like.

The salt of the compound selected from alanylglutamine, compound (I), prolylphenylalanine and compound (II) includes alkali metal salts such as sodium, potassium and lithium, and alkaline earth metal salts such as calcium and magnesium. , Ammonium salts and salts with amines such as monoethanolamine, triethanolamine, triisopropanolamine and the like, and these alkaline components are used alone or in the form of a mixture.

The dipeptide selected from alanylglutamine and prolylphenylalanine or the N-acyl dipeptide selected from compound (I) and compound (II) can be prepared by any production method such as synthetic method, enzymatic method or fermentation method. It may be a thing. As a method for producing alanylglutamine, for example, Bulletin The Chemical Society of Japan (Bull.Chem.Soc.
Jpn.), 34 , 739 (1961), 35 , 1966 (1962), 37 , 200 (196
4), European Patent No. 311057, German Patent No. 3206
No. 784, JP-A-6-234715, the method for producing prolyl phenylalanine is, for example, Journal of Organic Chemistry (J. Organ. Chem.), 32 , 3415 (1967), Bio Technology Letters (Biotech. Lett.) , 8 , 873 (1986) and JP-A-3-133391 can be used.

The N-acyl dipeptide selected from compound (I) and compound (II) can be produced, for example, by N-acyl alanine and carboxyl-protected glutamine, N.
-Condensation of acylproline and carboxyl-protected phenylalanine with a condensing agent such as dicyclocarbodiimide or carboxydiimidazole, followed by selective removal of the carboxyl-protecting group, or the amino group of alanylglutamine and prolylphenylalanine Can be acylated with a reagent such as carboxylic acid, acid anhydride or acid halide. For example, as a method for producing N-acetylalanylglutamine, the method described in JP-A-4-305596 and the like, and as a method for producing N-acetylprolylphenylalanine, Journal of Medicinal Chemistry (J. Med. Chem.), 31 , 2092 (1988) and the like.

The constituent amino acid moiety of the dipeptide and N-acyl dipeptide of the present invention may be any of L-form, D-form and DL-form. The dipeptide and N-acyl dipeptide of the present invention are contained in an amount of 0.01-10.0% by weight and 0.05-2.
It is blended in a proportion of 0% by weight. The cosmetics of the present invention include various components generally used in cosmetics, that is, oils and fats, hydrocarbons, waxes, fatty acids, synthetic esters, alcohols, surfactants, thickeners, humectants, and preservatives. A base such as a fragrance, a pigment, a drug, or water can be added.

Examples of the oils and fats include jojoba oil, castor oil, olive oil, soybean oil, coconut oil, palm oil, cocoa oil, mink oil, turtle oil, coconut oil, fatty acid diethanolamide and the like. Hydrocarbons include liquid paraffin, petrolatum, microcrystalline wax, squalane and the like.

Examples of waxes include beeswax, lanolin, carnauba wax and candelilla wax. Examples of the fatty acids include myristic acid, palmitic acid, stearic acid, oleic acid and isostearic acid. Synthetic esters include isopropyl myristate, isopropyl palmitate, butyl oleate, myristyl myristate, octyldecyl myristate,
Propylene glycol monostearate, myristyl lactate, isostearyl malate, glyceryl monostearate, distearyl dimethyl ammonium chloride and the like can be mentioned.

Oils and fats, hydrocarbons, waxes, fatty acids,
Synthetic esters are usually blended in a proportion of 0.01 to 30% by weight in total. As alcohols,
Examples thereof include ethanol, 1,3-butylene glycol, propylene glycol, lauryl alcohol, cetanol, stearyl alcohol, and oleyl alcohol.

The alcohols are blended in a proportion of 0.01 to 25% by weight.

As the surfactant, polyoxyethylene hydrogenated castor oil, sodium lauryl sulfate, polyoxyethylene glyceryl isostearate pyroglutamate,
Sodium alkylbenzenesulfonate, polyoxyethylene (10) stearyl ether, dialkylsulfosuccinic acid, cetylpyridinium bromide, n-octadecyltrimethylammonium chloride, monoalkylphosphoric acid, N-acylglutamic acid, sucrose fatty acid ester, polyoxyethylene (20) Examples thereof include sorbitan monostearate, sodium polyoxyethylene lauryl ether sulfate, and polyoxyethylene reduced lanolin.

The surfactant is preferably added in an amount of 0.01 to 5% by weight. However, in the case of shampoo, rinse, etc., it is mixed in a proportion of 0.01 to 40% by weight. Examples of the thickener include carboxyvinyl polymer, methylpolysiloxane, dextran, carboxymethylcellulose, carrageenan and hydroxymethylcellulose.

The thickener is usually added in a proportion of 0.01 to 5% by weight. Examples of the moisturizer include glycerin, propylene glycol, 1,3-butylene glycol, pyrrolidonecarboxylic acid, lactic acid and hyaluronic acid.
The moisturizer is blended in a proportion of 0.01 to 30% by weight.
Preservatives include benzoic acid, salicylic acid, dehydroacetic acid or salts thereof, phenols such as paraoxybenzoic acid ester, 2,4,4′-trichloro-2′-
Examples thereof include hydroxydiphenyl ether and 3-trifluoromethyl-4,4'-dichlorocarbanilide.

The preservative is added in a proportion of 0.01 to 0.5% by weight.

As the fragrance, any fragrance that is usually used for cosmetics may be used. As the pigment, iron oxide, titanium dioxide, zinc oxide, magnesium oxide, cesium oxide, talc, sericite, mica, titanium mica, montmorillonite, kaolin, alumina, silica, kaolin,
Muscovite, barium sulfate, aluminum silicate, aluminum magnesium silicate, sodium magnesium silicate, calcium silicate, calcium carbonate, nylon 6,
Examples include nylon 6.6, nylon powder, cellulose, crystalline cellulose, silk powder, and pumice powder.

The pigment is blended in a proportion of 0.01 to 90% by weight.

As the medicine, vitamin A, vitamin B ₂ , vitamin C, vitamin E and their derivatives,
D-pantotail alcohol, licorice extract, dipotassium glycyrrhizinate, placenta liquid, wheat germ oil,
Examples include glutathione.

The drug is blended in a proportion of 0.01 to 5% by weight. The dosage form of the cosmetic of the present invention is arbitrary. For example, a dosage form such as a solubilized system, an emulsified system, a dispersed system or a powder system can be adopted. As the cosmetic product of the present invention,
Basic cosmetics such as lotion, emulsion, cream, soap, pack, beauty essence, lipstick, foundation, eye shadow,
Makeup cosmetics such as eyeliner and manicure,
Hair cosmetics such as shampoo, conditioner, hair tonic, cologne are given. For alanylglutamine and prolylphenylalanine, lotion,
It is preferably used for hydrophilic cosmetics such as emulsions, creams, soaps, packs, shampoos, etc. For the compound (I) and the compound (II), in addition to the above cosmetics, a parent of hair tonic, cologne, manicure, etc. It is also suitably used for oily cosmetics.

Examples of the present invention will be shown below.

[0028]

【Example】

 Example 1 Lotion (1) Lotion (1) having the following formulation was produced.

[0029]

[Table 1]

(Preparation Method) One of the components shown in Table 1
To a liquid in which ~ 3 and 7 were uniformly mixed, a liquid in which 4 to 6 was uniformly mixed was added and mixed by stirring to obtain a product.

Example 2 Lotion (2) A lotion (2) having the same formulation as in Example 1 was prepared except that alanylglutamine was used instead of 2 of the components shown in Table 1.

Example 3 Emulsion (1) An emulsion having the following formulation was produced.

[0033]

[Table 2]

(Preparation Method) One of the components shown in Table 2
To ~ 5 solution heated and dissolved at 80 ℃, 6-8 and half amount of 11 solution heated and melted at 80 ℃ were added and mixed by stirring, and then homogenized 9, 10 and remaining 11 were added. After stirring and mixing, the product was cooled to room temperature.

Example 4 Emulsion (2) An emulsion (2) having the same formulation as in Example 3 except that prolylphenylalanine was used instead of 6 of the components shown in Table 2 was produced.

Example 5 Cream A cream having the following formulation was produced.

[0037]

[Table 3]

(Preparation Method) One of the components shown in Table 3
8 to 11 and 13 are added to a solution of ~ 7 heated and dissolved at 80 ° C.
Add the solution that was heated and dissolved at 0 ° C, mix with stirring, and
Was added and mixed by stirring, and then cooled to room temperature to obtain a product.

Example 6 Hair Tonic (1) A hair tonic (1) having the following formulation was produced.

[0040]

[Table 4]

(Preparation Method) One of the components shown in Table 4
A liquid obtained by heating and dissolving 6 to 9 at 80 ° C was added to the liquid obtained by mixing ~ 5 and 10, and the mixture was stirred and mixed to obtain a product.

Example 7 Cologne (1) Cologne (1) having the following formulation was produced.

[0043]

[Table 5]

(Preparation method) 2 out of the components shown in Table 5
To a liquid in which 1 and 3 were uniformly mixed, a liquid in which 1 was dissolved in 4 was added and mixed with stirring to obtain a product.

Comparative Example 1 Lotion (3) Lotion (3) having the same formulation as in Example 1 was prepared except that glycylglycine was used instead of 2 of the components shown in Table 1.

Comparative Example 2 Emulsion (3) An emulsion (3) having the same formulation as in Example 3 except that glycylglycine was used instead of 6 of the components shown in Table 2 was produced.

Comparative Example 3 Hair Tonic (2) A hair tonic having the same formulation as in Example 6 was prepared except that glycylglycine was used instead of 5 of the components shown in Table 4, and glycylglycine was produced. Was deposited. Therefore, a hair tonic (2) having the same formulation as in Example 6 was produced except that 5 of the components shown in Table 4 was removed.

Comparative Example 4 Oudecolone (2) An eaudecolone having the same formulation as in Example 7 was prepared except that glycylglycine was used instead of one of the components shown in Table 5, and glycylglycine was precipitated. did. Therefore, cologne (2) having the same formulation as in Example 7 was produced except that 1 of the components shown in Table 5 was omitted.

Test Example 1 Solubility Measurement Test In any one of 19.9 g of the solvents shown in Table 6, alanylglutamine, N-acetylalanylglutamine, prolylphenylalanine, N-acetylprolylphenylalanine and glycylglycine were added. 0.1 g each was added, and the mixture was gradually heated and stirred on a hot stirrer to dissolve it, and the solubility was evaluated.

The results are shown in Table 6.

[0051]

[Table 6]

As is clear from Table 6, N-acetylalanylglutamine and N-acetylprolylphenylalanine showed high solubility in organic solvents.

Test Example 2 Sensory test of lotion lotion Lotion lotion (1) obtained in Examples 1 and 2 and Comparative Example 1,
Using (25) specialized panelists, (2) and (3) were evaluated according to the following scoring table for three items: (a) moisturizing property, (b) skin familiarity, and (c) skin penetration feeling. .

Table 7 shows the results of applying the test lotion to the face twice a day in the morning and evening and continuously for one month.

[0055]

[Table 7]

Test Example 3 Emulsion sensory test The emulsions (1) obtained in Examples 3 and 4 and Comparative Example 2,
Using (25) specialized panelists, (2) and (3) were evaluated according to the following scoring table for 3 items: (a) moisturizing property, (b) skin familiarity, and (c) spreadability. Table 8 shows the results of applying the test emulsion to the face twice a day in the morning and evening and continuously for one month.

[0057]

[Table 8]

Test Example 4 Hair tonic sensory test Hair tonic (1) obtained in Example 6 and Comparative Example 3
And (2) using 25 specialized panelists respectively (a) moisturizing the skin, (b) familiarizing with the skin,
(C) Three items of spread to the background were evaluated according to the following scoring table. Test hair tonic twice a day, morning and evening,
The results of continuous application to the scalp for one month are shown in Table 9.

[0059]

[Table 9]

Test Example 5 Sensory test of cologne Cologne (1) obtained in Example 7 and Comparative Example 4
Using (25) specialized panelists, (2) the suppleness of the skin and (b) the smoothness of the skin were evaluated according to the following scoring table. Table 10 shows the results obtained by applying the test cologne to the upper arm once a day in the morning and continuously for one month.

[0061]

[Table 10]

Reference Example 1 N-acetyl-L-alanyl-
Synthesis of L-glutamine L-alanyl-L-glutamine (manufactured by Kyowa Hakko Kogyo Co., Ltd., hereinafter abbreviated as alanylglutamine) 31.9 g (14
6.7 mmol) in 40 ml of water, and the pH is adjusted to 8.0 to 8.
While keeping at 5, acetic anhydride 16.4g (161.4mmo
1) was added dropwise and reacted. After completion of the reaction, concentrated hydrochloric acid was added to the reaction solution to adjust to pH 2.0, and this was concentrated. 200 ml of toluene was added to the concentrated liquid, and the remaining water was removed by azeotropic distillation. After removing water, toluene was distilled off to obtain a residue, to which 200 ml of ethanol was added,
It was heated and dissolved. The solution is filtered in a heated state,
After separating the filtrate and the undissolved residue, the residue was thoroughly washed with ethanol. The filtrate and washings were combined and concentrated to about 80 ml. The concentrated liquid was cooled and the precipitated crystals were collected by filtration and dried under reduced pressure to obtain 19.7 g of N-acetylalanylglutamine as crystals.

The physicochemical properties of N-acetylalanylglutamine are as follows. Properties: White powder Melting point: 182 to 184 ℃ Specific rotation: [α] _D ²⁵ = -38.0 ° (c = 1.02, CH ₃ OH) UV absorption spectrum (CH ₃ OH solution): λ _max nm (ε) 205.0 ( 2680) infrared absorption spectrum (KBr, ^{_{tablet): ν max cm -1 3485,3363,3325,3292,1720,1668,1612,1550,1232 1}} H-NMR spectrum (400MH _z, CD ₃ OD solution): [delta] ppm ( Multiplicity, coupling constant) 1.35 (d, J = 7.3), 1.88 to 1.96 (m), 1.98 (s), 2.18 to 2.37 (m),
4.33 (q, J = 7.3), 4.40 (m) ¹³ C-NMR spectrum (400MH _Z , CD ₃ OD solution): δppm (multiplicity) 17.79 (q), 22.39 (q), 28.59 (t), 32.57 ( t), 50.54 (d), 53.04
(d), 173.24 (s), 174.71 (s), 175.33 (s), 177.76 (s) FAB-MS spectrum (matrix: glycerol): m /
z 260 (M + H) ⁺ HR-FAB-MS: C ₁₀ H ₁₈ N ₃ O ₅ Actual value: 260.1243 Calculated value: 260.1247 Elemental analysis Actual value: (100 ° C overnight vacuum drying) C: 44.92, H: 6.58 , N: 15.87 Calculated: C ₁₀ H ₁₇ N ₃ O ₅・ 1 / 2H ₂ OC: 44.76, H: 6.77, N: 15.67

Reference Example 2: N-acetyl-L-prolyl-
Synthesis of L-phenylalanine L-prolyl-L-phenylalanine (Kyowa Hakko Kogyo KK, hereinafter abbreviated as prolylphenylalanine) 31
4.8 g (1.2 mol) was suspended in 3140 ml of water,
PH below 15 ° C with 4N aqueous sodium hydroxide
138.0 g of acetic anhydride while keeping the value of 8.0-8.5
(1.3 mol) was added dropwise to react.

After the reaction was completed, the reaction solution was filtered, and concentrated hydrochloric acid was added to the obtained filtrate to adjust the pH to 2.0. The precipitated crystals were collected by filtration, washed with 3 L of water, and dried under reduced pressure to obtain 650 g of N-acetylprolylphenylalanine as crystals. The physicochemical properties of N-acetylprolylphenylalanine are as follows. Properties: White powder Melting point: 208-210 ° C Specific rotation: [α] _D ²⁵ = -27.8 ° (c = 1.01, CH ₃ OH) UV absorption spectrum (CH ₃ OH solution): λ _max nm (ε) 263.0 ( 143), 257.5 (188), 252.0 (161), 246.5 (135), 212.5
(6490) Infrared absorption spectrum (KBr, tablet): ν _max cm ^-1 3325,2987,2956,1736,1657,1595,1550,1263,1223,702 ¹ H-NMR spectrum (400NH _Z , CD ₃ OD solution) : Δppm (Multiplicity) 1.67 (s), 1.67 ~ 1.83 (m), 1.86 ~ 2.06 (m), 2.06 (s), 2.06 ~
2.27 (m), 2.92 to 3.06 (m), 3.19 (m), 3.33 to 3.60 (m), 4.28
(m), 4.45 (m), 4.67 (m), 4.78 (m), 7.17 to 7.30 (m) ¹³ C-NMR spectrum (400 MHz _Z , CD ₃ OD solution): δppm (multiplicity) 22.05 (q), 22.18 (q), 23.62 (t), 25.49 (t), 30.41 (t), 32.90
(t), 38.05 (t), 38.26 (t), 47.91 (t), 49.32 (t), 54.58 (d), 5
4.93 (d), 61.02 (d), 62.58 (d), 127.78 (d), 127.82 (d), 129.
39 (d), 129.51 (d), 130.16 (d), 130.44 (d), 138.21 (s), 138.
71 (s), 172.60 (s), 172.80 (s), 174.14 (s), 174.22 (s), 174.
37 (s) FAB-MS spectrum (matrix: glycerol): m /
z 305 (M + H) ⁺ HR-FAB-MS: C ₁₆ H ₂₁ N ₂ O ₄ Found: 305.1494 Calculated: 305.1502 Elemental analysis Found: C: 62.92, H: 6.71, N: 9.09 Calculated: C ₁₆ H ₂₀ N ₂ O ₄ C: 63.14, H: 6.62, N: 9.20

[0066]

EFFECTS OF THE INVENTION According to the present invention, it is possible to provide a cosmetic having excellent moisturizing properties, good compatibility with the skin, and excellent usability.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07K 5/078 8517-4H C07K 5/078

Claims (1)

[Claims] 1. Alanylglutamine, a compound represented by the general formula (I): (Wherein R ¹ represents a hydrogen atom or lower alkyl), N-acyl alanyl glutamine, prolyl phenylalanine, a compound represented by the general formula (II): A cosmetic comprising one or more compounds selected from N-acylprolylphenylalanine represented by the formula (wherein R ² represents a hydrogen atom or lower alkyl) and salts thereof.