JP2006131522A - Cosmetic - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop a zinc compound having high stability in a wide pH range, high in safety to skin and having high effectiveness, and to prepare a cosmetic containing the same. <P>SOLUTION: The developed zinc (II) complex contains a zinc source and ligands comprising amino acids and oligopeptides, each being a biological material, and compounds as their derivatives. This zinc (II) complex is lower in toxicity than a zinc (II) ion, has high stability in a wide pH range and high effectiveness, and can be blended in the cosmetic. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a cosmetic comprising a zinc (II) organic complex having as a ligand a compound comprising a biological substance such as amino acids, oligopeptides, and derivatives thereof.

Conventionally, zinc oxide, which is a zinc compound, and inorganic salts such as zinc sulfate, zinc acetate, and zinc chloride have been blended into cosmetics in anticipation of an anti-inflammatory effect. However, since zinc (II) ions are difficult to pass through the biological membrane, they are not easily taken into the living body, and a sufficient effect cannot be expected.

In Japanese Patent Publication No. 2002-516838, the amino acid complex of zinc restores the elasticity of the skin by promoting the adhesion of keratinocytes in the dermis epidermis junction, particularly the epidermis basal layer to the collagen at the junction. Although there is a description about the cosmetic treatment method to be performed, it is in a situation where it cannot be expected to have an effect on prevention of UV damage, improvement of spots, and improvement of rough skin.

Japanese National Patent Publication No. 2002-516838

An object of the present invention is to develop a zinc compound having high stability in a wide pH range, high safety to the skin, and high effectiveness. In general, a compound having two or more amino groups, carboxyl groups, and hydroxyl groups in the molecule easily forms a complex chelate compound with zinc ions. However, when these chelate compounds are in an alkaline region having a pH of 8 or more, precipitation occurs, which hinders blending into cosmetics.

As a result of intensive studies to overcome the above-mentioned problems, the present invention has been developed as a zinc (II) complex that is less toxic than zinc (II) ions, has high stability in a wide pH range, and has a high skin-beautifying effect. A zinc (II) complex comprising a ligand consisting of amino acids, oligopeptides which are substances, and compounds which are derivatives thereof and a zinc source has been developed and can be incorporated into cosmetics.

Since the zinc (II) complex of the present invention protects cells from UV damage and exhibits a strong anti-inflammatory effect, it is expected to develop cosmetics with high wrinkle improvement, blemishes improvement, and rough skin improvement effects when formulated in cosmetics. Is done. Moreover, since the zinc complex of this invention uses the biological component which consists of an amino acid as a ligand and has high safety | security when it apply | coats to skin, it is useful also as a skin external preparation.

Although there will be no restriction | limiting in particular if the compounding quantity of the zinc complex in the cosmetics of this invention is effective, 0.0001-5.0 weight% is preferable and the range of 0.01-1.0 weight% is still more preferable.

The zinc source used in the present invention is not particularly limited as long as it is a zinc source suitable for human administration, and examples thereof include zinc acetate, zinc chloride, zinc sulfate, and zinc nitrate. When a zinc mineral salt is used as the zinc source, a basic aqueous solution such as potassium hydroxide, sodium hydroxide, lithium hydroxide, or barium hydroxide may be used in combination as a pH adjuster. The ligands that form the zinc complex include threonine, valine, leucine, isoleucine, glycine, proline, arginine, glutamine, glutamic acid, asparagine, aspartic acid, alanine, histidine, lysine, serine, methionine, phenylalanine, tyrosine, cysteine. , Derivatives such as tryptophan, betaine, theanine, and amides thereof, and oligopeptides such as dipeptides and tripeptides, or derivatives thereof.

The cosmetics of the present invention are cosmetics, quasi-drugs, aqueous ingredients used in pharmaceuticals, oily ingredients, plant extracts, animal extracts, powders, surfactants, oils, alcohols, pH adjustments in addition to the above essential ingredients An agent, preservative, antioxidant, thickener, pigment, fragrance, and the like are mixed as necessary and blended as appropriate. The dosage form of the cosmetic of the present invention is not particularly limited, and can be various dosage forms such as lotion, milky lotion, cream, pack, powder, spray, ointment, dispersion, and detergent.

Examples of preparation of zinc complex according to the present invention, effect test in cells, and effect test in humans are shown below. Furthermore, although the application prescription example etc. to the cosmetics using the raw material are described, it cannot be overemphasized that it is not limited to the Example described here.

[Preparation of proline-zinc complex]
(Solution Preparation 1)
1) Proline solution: 8 g of proline is dissolved in 50 ml of purified water.
2) Zinc sulfate solution: 10 g of zinc sulfate heptahydrate is dissolved in 30 ml of purified water.
3) Add 15.0 g of glycine and 14,7 g of L-glutamic acid to 50 ml of purified water, stir at 100 ° C. for 5 hours and dissolve. Add the proline solution prepared in advance to this and stir well. Add zinc sulfate solution and stir well. After cooling, adjust to pH 6.5 with 2N-NaOH. Finally, make up to 255 ml with purified water. The proline-zinc complex is present in this solution at 4 w / v%.
The solution was stable in a wide pH range without causing precipitation even at pH 13.0.

[Preparation of glutamine-zinc complex]
(Solution Preparation 2)
1) L-glutamine solution: 10.2 g of L-glutamine is dissolved in 50 ml of purified water.
2) Zinc acid solution: 10 g of zinc sulfate heptahydrate is dissolved in 30 ml of purified water.
3) Add 15.0 g of glycine and 14,7 g of L-glutamic acid to 50 ml of purified water, stir at 100 ° C. for 5 hours and dissolve. Add the proline solution prepared in advance to this and stir well. Add zinc sulfate solution and stir well. After cooling, the pH is adjusted to 6.5 with 2N-NaOH. Finally, make up to 250 ml with purified water. In this solution, 5 w / v% of L-glutamine-zinc complex is present.
The solution was stable in a wide pH range without causing precipitation even at pH 13.0.

Table 1 shows the stability of the prepared zinc complex with changes in pH. The pH of the aqueous zinc sulfate solution was 5.3, but immediately after the addition of sodium hydroxide, precipitation occurred. The zinc complexes prepared in Solution Preparations 1 and 2 and other amino acid complexes were stable without precipitation at high pH.

[Measurement of effect]
(Confirmation of UV injury protection effect)
5 × 10 ⁴ human skin normal keratinocytes are planted per well in a 12-well petri dish. 10 μM of each sample is added to the medium in each well and incubated for 24 hours. After removing the medium and washing with PBS (−), 20 mJ / cm ² of UV-B is irradiated. After irradiation, the number of cells cultured for 48 hours is counted.
To measure the number of cells, the cells are fixed with neutral formalin and then stained with 1 ml of 0.05% amide black (9% acetic acid, 0.1M Na acetate) for 30 minutes. After staining, the dye was extracted with 0.4 ml of 0.05N NaOH and the absorbance at 595 nm was measured to obtain the number of cells. The following serum-free medium was used as a medium for culturing keratinocytes.

Medium: Bullet kit EGM (modified MCDB
131 medium)

Additives: Bovine brain extract (BBE) 12μg / ml, h-EGF 0.01μg / ml, Hydrochotson 1μg / ml, Gentamicin 50mg / ml, Amphotericin
50μg / ml

Table 2 shows the results of tests using 10 newly prepared amino acid zinc complexes, a zinc sulfate aqueous solution as a comparative control, and zinc gluconate conventionally used in cosmetics. Assuming that the cell growth rate of the test group not irradiated with ultraviolet rays is 100, the cell growth rate of the test group irradiated with ultraviolet rays of 20 mJ / cm ² is reduced to 60%, and the cell growth is impaired by the ultraviolet rays. Recognize. In addition, in the test group to which zinc gluconate was added, cell proliferation was 70%, and an effect of preventing UV damage to some extent was recognized. On the other hand, all the test plots to which the amino acid zinc complex had been added showed cell proliferation of 80% or more except for 77% of the serine zinc complex, and the damage to cells due to ultraviolet rays was clearly reduced. I understood.

[Confirmation of anti-inflammatory effect]
Apply 15μl of sample to Torii patch van (mini size) and apply to the inner skin of upper arm for 4 hours. Sample types are 10% SDS (sodium dodecyl sulfate) aqueous solution as a flame retardant, 5% aqueous solution of proline zinc complex, 5% aqueous solution of zinc gluconate, and 5% aqueous solution of dipotassium glycyrrhizinate as active ingredients. A sample was prepared and attached.

The results of observing the skin condition 24 hours after peeling the torii patch van are shown in Table 3. Table 4 shows the evaluation criteria for skin reaction. As shown in Table 3, the 10% SDS aqueous solution application group showed clear erythema. In addition, in the sample to which 10% of 5% aqueous solution of dipotassium glycyrrhizinate widely used in cosmetics as an anti-inflammatory agent was added, slight erythema was observed and a sufficient anti-inflammatory effect was not observed. In contrast, in the sample to which 5% of the 5% aqueous solution of proline zinc complex was added, no erythema was observed, indicating that it exhibited a strong anti-inflammatory effect. On the other hand, slight erythema was observed in the test group to which 10% zinc sulfate 5% aqueous solution was added and in the test group to which 5% zinc gluconate 5% aqueous solution was added, and the anti-inflammatory effect was low compared to the proline zinc complex. It became clear.

Next, although the formulation example of the cosmetics which mix | blended various components of this invention is shown, this invention is not limited to this.

[Cosmetic cream]
(component)
(weight%)
a) Beeswax
2.0
b) Stearyl alcohol 5.0
c) Stearic acid
8.0
d) Squalane
10.0
e) Self-emulsifying glyceryl monostearate
3.0
f) Polyoxyethylene cetyl ether (20E.O.)
1.0
g) Proline zinc complex
0.01
h) 1,3-butylene glycol
5.0
i) Potassium hydroxide

0.3
j) Preservatives and antioxidants
Appropriate amount
k) Purified water
The rest of the manufacturing method: a) to f) are dissolved by heating and kept at 80 ° C. G) to k) are dissolved by heating, kept at 80 ° C., and added to a) to f) to emulsify. Cool to 40 ° C with stirring.

[Emulsion]
(component)
(weight%)
a) Beeswax
0.5
b) Petrolatum
2.0
c) Squalane
8.0
d) Sorbitan sesquioleate
0.8
e) Polyoxyethylene oleyl ether (20E.O.) 1.2
f) d-δ-tocopherol

1.0
g) Glutamine zinc complex
1.0
h) 1,3-butylene glycol
7.0
i) Carboxyvinyl polymer

0.2
j) Potassium hydroxide

0.1
k) Purified water

The rest
l) Preservatives and antioxidants

Appropriate amount
m) ethanol

7.0
Manufacturing method: Heat up to a) to f) and keep at 80 ° C. G) to l) are heated and dissolved, kept at 80 ° C., added to a) to e), emulsified, and cooled to 50 ° C. with stirring. Add m) at 50 ° C. and stir cool to 40 ° C.

[Emulsion]
(component)
(weight%)
a) Beeswax
0.5
b) Petrolatum
2.0
c) Squalane
8.0
d) Sorbitan sesquioleate
0.8
e) Polyoxyethylene oleyl ether (20E.O.) 1.2
f) Zinc methionine complex
5.0
g) Dipotassium glycyrrhizinate 0.1
h) 1,3-butylene glycol
7.0
i) Carboxyvinyl polymer
0.2
j) Potassium hydroxide
0.1
k) Purified water
The rest
l) Preservatives and antioxidants
Appropriate amount
m) ethanol
7.0
Process: Heat up to a) to e) and keep at 80 ° C. F) to l) are heated and dissolved, kept at 80 ° C., added to a) to e), emulsified, and cooled to 50 ° C. with stirring. Add m) at 50 ° C. and stir cool to 40 ° C.

[Lotion]
(component)
(weight%)
a) Zinc valine complex
0.001
b) Glycerin
5.0
c) Polyoxyethylene sorbitan monolaurate (20E.O.) 1.0
d) ethanol
6.0
e) Fragrance
Appropriate amount
f) Preservatives and antioxidants
Appropriate amount
g) Purified water
The rest
h) Hyaluronic acid 0.1
Production method: a), b), g) and h) are mixed uniformly. c) to f) are mixed uniformly and added to the mixture a), b), g), h).

[Lotion]
(component)
(weight%)
a) Alanine zinc complex
0.0001
b) 1,3-butylene glycol
8.0
c) Polyoxyethylene sorbitan monolaurate (20E.O.) 1.0
d) ethanol
6.0
e) Fragrance
Appropriate amount
f) Preservatives and antioxidants
Appropriate amount
g) Purified water The remaining preparation method: a), b) and g) are mixed uniformly. c) to f) are mixed uniformly and added to the mixture a), b), g).

[Facial cleanser]
(component)
(weight%)
a) Glycine zinc complex
0.1
b) Talc
The rest
c) Cellulose
20.0
d) Potassium myristate
30.0
e) Sodium lauryl phosphate
10.0
f) Fragrance
Appropriate amount
g) Preservatives
Appropriate amount of production method: a) to g) are mixed, stirred and dispersed well to make uniform.

As described above in detail, the amino acid zinc complex of the present invention has a high protective effect against ultraviolet ray damage and an anti-flame effect, and the cosmetics containing this can be applied to anti-wrinkle, anti-stain, skin roughening cosmetics and skin external preparations. It is.

Claims (4)

A cosmetic comprising a ligand and a zinc source, which are compounds that can form a complex with zinc and are amino acids, oligopeptides, and derivatives thereof. The cosmetic according to claim 1, wherein the zinc source is a mineral salt of zinc. Amino acids are threonine, valine, leucine, isoleucine, glycine, proline, arginine, glutamine, glutamic acid, asparagine, aspartic acid, alanine, histidine, lysine, serine, methionine, phenylalanine, tyrosine, cysteine, tryptophan, betaine, theanine, and The cosmetic according to claim 1 or 2, which is one or more compounds selected from the group consisting of derivatives of these amino acids. The cosmetic according to claim 1 or 2, wherein the oligopeptide is one or more compounds selected from the group consisting of dipeptides and tripeptides, or derivatives thereof.