JPH0543442A - Skin cosmetic - Google Patents

Abstract

PURPOSE:To obtain a skin cosmetic, containing a basic fibroblastic growth factor containing a polypeptide having a specific amino acid sequence as an active ingredient, capable of improving skin roughening by sunburn and excellent in skin beautifying effects for preventing aging phenomena of the skin such as fine wrinkles. CONSTITUTION:A skin cosmetic containing a basic fibroblastic growth factor(bFGF), which is especially a polypeptide having an amino acid sequence expressed by the formula as an active ingredient. The bFGF is a basic polypeptidic cell growth factor found from the hypophysis of cattle and obtained from naturally occurring substances or by mass production according to a peptide synthetic method or genetic recombination technology. The cosmetic is capable of exhibiting excellent skin beautifying effects and useful and simultaneously has high safety for the skin.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin cosmetic having an excellent skin beautifying effect. More specifically, the present invention relates to a novel skin cosmetic containing a basic fibroblast growth factor (bFGF), which improves skin roughness caused by sunburn and improves fine wrinkles on the skin, and which has an excellent skin-beautifying effect.

[0002]

2. Description of the Related Art Unlike other organs, the skin is susceptible to external influences, that is, physical factors such as sunlight, temperature and humidity, or chemical factors such as detergents. Among them, the adverse effect of ultraviolet rays contained in sunlight on the skin is particularly serious. That is, when the skin is exposed to ultraviolet rays for a long time to cause sunburn, the skin is damaged, inflammation is caused, and the skin is weakened and blisters are changed. When such a state is repeated, collagen fibers in the subcutaneous tissue are destroyed, and aging of the skin such as rough skin and wrinkles is promoted.

It is known that the wavelength that causes inflammation such as erythema on human skin is a medium-wave ray (UV wavelength range) of about 280 to 320 nm.

Therefore, cosmetics intended to prevent sunburn generally have a U.S.P. V. A compound that selectively absorbs ultraviolet rays in the B wavelength range and 308 nm which is said to cause erythema in particular
It is known that a compound having a maximum absorption value, for example, salicylic acid, para-aminobenzoic acid and its esters, and a cinnamic acid derivative are compounded.

However, these conventionally known sunscreen cosmetics are mainly U.S. Pat.
V. Although it protects against sunburn by absorbing ultraviolet rays in the B wavelength range, the effect of preventing sunburn is not always sufficient, and it is completely effective as an external preparation that effectively prevents inflammation due to sunburn. Not only
Like salicylic acid, it also has problems such as side effects on the skin.

[0006] On the other hand, various chemicals are used as cosmetics for preventing skin roughening, but they are effective in improving the rough skin roughening accompanied by inflammation due to sunburn and are one of the skin aging phenomena. No cosmetics have been found that have excellent skin-beautifying effects for improving such problems such as wrinkles and fine lines.

[0007]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a skin cosmetic having an excellent skin beautiful effect for improving skin roughness caused by sunburn and preventing skin aging such as fine lines. It is in.

[0008]

[Means for Solving the Problems] The inventors of the present invention have conducted extensive studies to achieve the above object.

As a result, as an amino acid sequence, Phe-Phe-Leu-Arg-Ile-His-P
ro-Asp-Gly-Arg-Val-Asp-Gl
y-Val-Arg-Glu-Lys-Ser-Asp
-BFGF containing the polypeptide represented by Pro improves the skin roughness accompanied by inflammation due to sunburn,
The present invention has been completed by discovering that it has an antiaging effect on skin such as fine wrinkles.

BFGF was introduced in 1974 by Gospoda.
is a basic peptide growth factor found in bovine pituitary gland by Rowicz [D. Gosp
odarowicz; Nature 24
9: 123 (1974)], as commercially available products, for example, bovine brain-derived bFGF (trade name: bFGF (b)), bovine pituitary-derived bFGF (trade name: BASIC) sold by Funakoshi Yakuhin Co., Ltd. FIBROBL
AST GROWTH FACTOR) and the like can be used in the present invention. Initially, bFGF was isolated as a growth stimulator of B _ALB / _C 3T3 cells, but was subsequently shown to have activity on almost all mesodermally-derived cells including vascular endothelial cells.

The use of bFGF as an anti-ulcer agent and an agent for improving stinging has been studied so far, but there has been no study of its usefulness by incorporating bFGF into skin cosmetics as in the present invention. ..

[0012] That is, the present invention provides a novel skin cosmetic characterized by containing a basic fibroblast growth factor (hereinafter sometimes simply referred to as bFGF) as an active ingredient.

The bFGF which can be used in the present invention is Phe-Phe-Leu-Arg-Ile-His-P.
ro-Asp-Gly-Arg-Val-Asp-Gl
y-Val-Arg-Glu-Lys-Ser-Asp
It includes a polypeptide having an amino acid sequence represented by -Pro, and naturally occurring ones as well as those obtained by mass production by peptide synthesis methods and gene recombination techniques can be used.

In the above amino acid sequence, Phe is phenylalanine, Leu is leucine, Arg is arginine, Ile is isoleucine, His is histidine, Pro is proline and Asp is aspartic acid.
Gly means glycine, Val means valine, Glu means glutamic acid, Lys means lysine, and Ser means serine.

The natural substances that can be used in the present invention include:
“Procedures of the National Academy of the United States of America (Proc. Natl. Acad. Sci. US
A) ", vol. 82, pages 6507-6511 (1985).
, Etc., such as bovine pituitary gland,
Molecular weight 15-18 KDa, pI 9.6 isolated from brain, retina, luteum, adrenal gland, kidney, placenta, prostate, thymus, etc.
A heparin-binding protein having 146 amino acids can be mentioned. As a method for peptide synthesis, Phe-Phe-
Leu-Arg-Ile-His-Pro-Asp-G
ly-Arg-Val-Asp-Gly-Val-Ar
Peptides having the amino acid sequence of g-Glu-Lys-Ser-Asp-Pro and those produced by the gene recombination technique include those described in JP-A-2-193, and the molecular weight is not particularly limited, Protein containing at least one amino acid sequence, at least one bFG
Examples thereof include those lacking the F constituent amino acids and those in which at least one bFGF constituent amino acid has been replaced with another amino acid, such as muteins in which cysteine has been replaced with serine.

The skin cosmetic of the present invention includes quasi-drugs and cosmetics, and its dosage forms include various externally applicable forms such as cream, ointment, emulsion, lotion, emulsion, essence, pack, and the like. It can be used by formulating it into a known form such as gel, and its base material can be widely used in any liquid and solid raw materials which are acceptable for skin application.

At this time, various additives such as antiseptics, fragrances, stabilizers, colorants, ultraviolet absorbers, antioxidants, humectants and thickeners can be added, if necessary.

BF which is an active ingredient of the skin cosmetic composition of the present invention
The amount of GF may be appropriately changed depending on the application site, the degree of symptoms, the dosage form, etc., but it is usually 200 to 2,000,000.
0 unit or so, preferably 2,000 to 1,000,000
About 0 unit is included in the formulation.

Here, the activity that doubles the thymidine uptake amount is defined as 1 unit.

This active ingredient can be used alone or in combination with an active ingredient usually used in skin cosmetics. For example, cepharanthin, vitamin E, vitamin E nicotinate, nicotinic acid, nicotinic acid amide, benzyl nicotinate, Peripheral vasodilators such as ginger tincture and capsicum tincture, cooling agents such as camphor and menthol,
Antibacterial agents such as hinokitiol, base benzalkonium, and undecylenic acid, anti-inflammatory agents such as lysozyme chloride, glycyrrhizin, and allantoin, whitening agents such as ascorbic acid, arbutin, and kojic acid, assemblage extract, garlic extract, carrot extract, sardine extract, rose. Various extracts derived from animals or plants such as marie extract, aloe extract, placenta extract and liver extract can be appropriately selected and used freely.

Next, examples of skin cosmetics of the present invention and test examples of their effects will be shown, but these do not limit the present invention at all.

[0022]

EXAMPLES Example 1 Cream Bovine brain-derived bFGF 20,000 units (wt%) A Monostearic acid 2.0 Polyethylene glycol (40.EO) Self-emulsifying glyceryl monostearate 5.0 Stearic acid 5.0 Behenyl alcohol 1.0 Liquid paraffin 10.0 Glyceryl trioctanoate 10.0 B Glycerin 5.0 Elparaben 0.1 Purified water Appropriate amount The components belonging to A are dissolved by heating. Separately, the components belonging to B are melted by heating. BF which is an active ingredient by adding B to A
GF was added, and the mixture was stirred, emulsified, and cooled to produce a cream.

Example 2 Emulsion bFGF mutein 10,000 units (mutein in which two cysteines were replaced by serine) (% by weight) A Polyoxyethylenesorbitan monostearate (20.EO.) 1.0 Monostearin Acid polyoxyethylene sorbit (60.EO) 0.5 Lipophilic glyceryl monostearate 1.0 Stearic acid 0.5 Behenyl alcohol 0.5 Avocado oil 4.0 Glyceryl trioctanoate 4.0 B 1,3 -Butylene glycol 5.0 Methylparaben 0.2 Purified water Appropriate amount The components belonging to A are dissolved by heating. Separately, the components belonging to B are melted by heating. BF which is an active ingredient by adding B to A
GF mutein was added, stirred, emulsified, and cooled to prepare an emulsion.

Example 3 Lotion Lotion Synthetic peptide having bFGF activity 500,000 units (% by weight) Polyoxyethylene hydrogenated castor oil (60.EO.) 8.0 Ethanol 15.0 Ethylparaben 0.1 Glycerin 2 0.0 1,3-butylene glycol 4.0 Disodium edetate 0.01 Purified water Appropriate amount The above components were mixed, uniformly stirred and dissolved to produce a lotion.

Example 4 Cream pack bFGF (obtained by genetic recombination) 20,000 units [Product name: RECOMBINANT FIBROBLAST GROWTH FACTOR, BASIC, sold by Funakoshi Chemical Co., Ltd.] (% by weight) A Veegum 5.0 Squalane 2.0 Propylene Glycol 5.0 Vitamin B ₁₂ 0.05 Purified water Appropriate amount B Zinc oxide 10.0 C Ethanol 5.0 Mix components belonging to A, swell by stirring, and add B little by little. C was gradually added to this, and bFGF was further added and kneaded until a paste was formed to prepare a cream pack.

Example 5 Essence (% by weight) bFGF 200,000 units (mutein in which two cysteines are replaced by serine) 1% carboxyvinyl polymer solution 10.0 glycerin 20.0 hyaluronic acid 0.5 ethanol 1.0 Purified water Appropriate amount The above components were mixed, uniformly stirred and dissolved to produce an essence.

Example 6 Hydrophilic Ointment (wt%) Naturally occurring bFGF 0.01 A Polyoxyethylene cetyl ether 2.0 Glyceryl monostearate 10.0 Liquid paraffin 10.0 Vaseline 4.0 Cetanol 5.0 B Propylene glycol 10.0 Methylparaben 0.1 Purified water Appropriate amount The components belonging to A are dissolved by heating. Separately, the components belonging to B are dissolved by heating. BF which is an active ingredient by adding B to A
After adding GF, stirring and emulsifying, cooling was performed to produce a hydrophilic ointment.

[Test Example] Test Example 1 Observation and Measurement of Skin Surface by Replica Method a) Test Method A skin having a re-replica score of 1 by ultraviolet irradiation (there is a disappearance of skin crevices / hills and a wide range of skin). Fifty subjects having corneal exfoliation are randomly distributed into two groups, the cream prepared in Example 1 is used in the first group, and the base (Example 1) is used in the second group. 0.3 ± 0.1 g of the cream (excluding the active ingredient bFGF) from 2
It was applied once every 12 hours, and the surface condition of the skin at the start of application and one week after the application was taken as a replica, and the result was observed with a stereoscopic microscope (20 times).

The replica is obtained by the method of Kumagai et al. [SCCJ. V
ol 19, No. 1 (1985) p. 9 to 19], a negative replica was taken on the skin surface using a quick-drying silicone synthetic rubber, and a polysulphide synthetic rubber was filled in the negative replica to obtain a positive replica.

B) Test Results The results are shown in Table 1 below.

[0031]

[Table 1]

<Evaluation Classification of Skin Surface Condition> Evaluation 1: Disappearance of skin groove / concrete and wide exfoliation of stratum corneum are recognized.

2: The sulcus and crust are unclear, and peeling of the stratum corneum is observed.

3: Although there are some pits and ridges, they are flat and flow in one direction.

4: Defects and cuticles are clear.

5: Clear skin grooves and cuts arranged in a mesh pattern.

As described above, b which is the active ingredient of the present invention
It is clear that FGF has an excellent effect of improving damaged skin.

Test Example 2 Wrinkle Improvement Effect Test by Half Face Method a) Test Method The essence of the present invention (Example 5) was tested by 30 women (3
5 to 55 years old), apply to face continuously twice a day in the morning and evening.
After a month, the degree of improvement of small wrinkles was examined. Apply on face
The half-face method is performed on the left and right sides, and the essence of the present invention is used for one side and bFGF for the other side as a control.
What did not contain (base only) was applied and evaluated.

B) Test Results As a result of judging the degree of improvement of small wrinkles before the use of essence, the essence of the present invention was found to have a clear effect of improving small wrinkles. In addition, no skin abnormality was observed after continuous use. The results are shown in Table 2.

[0040]

[Table 2]

[0041]

EFFECTS OF THE INVENTION According to the present invention, a novel skin cosmetic containing a basic fibroblast growth factor (bFGF) as an active ingredient is provided, and by applying it to the skin, it is possible to improve the skin damaged by sunburn. It can be achieved very effectively and can prevent skin aging such as fine lines. In addition, it is a useful skin cosmetic that is highly safe to the skin.

Claims (2)

[Claims] 1. Basic fibroblast growth factor (bFGF)
A skin cosmetic comprising the following as an active ingredient. 2. bFGF has an amino acid sequence of Phe-Phe-Leu-Arg-Ile-His-P.
ro-Asp-Gly-Arg-Val-Asp-Gl
y-Val-Arg-Glu-Lys-Ser-Asp
The skin cosmetic according to claim 1, which is a polypeptide containing -Pro.