JPH0867620A - Skin activator having glycosaminoglycan production-accelerating action - Google Patents

Abstract

PURPOSE: To obtain a skin activator having an exceeding glycosaminoglycan production-accelerating action and useful as a cosmetic and a skin aging- inhibiting external application by using a specific lysophospholipid having high safety as an active component. CONSTITUTION: This skin activator having glycosaminoglycan production- accelerating action contains a compound expressed by the formula (M is H or an alkali metal) as an active component. This activator is an aging-inhibiting cosmetic aiming for giving a springiness to skin and inhibiting wrinkles. The mixing ratio of the compound expressed by the formula is preferably 0.01-10wt.% of total volume of the skin external application or a medicine. The compound expressed by the formula is obtained. e.g. by treating 1- decanoyl-2-acyl-phosphatidic acid with phosphilipase A2. A new and exceeding glycosaminoglycan production-accelerating material is offered by the above method and the skin-activating external application containing the compound as an active component manifests an excellent skin-beautifying effect.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin activating agent containing a 1-acyl lysophospholipid derivative as an active ingredient and having a glycosaminoglycan production promoting action. This skin activating agent is useful as a cosmetic and an external preparation for preventing skin aging.

[0002]

2. Description of the Related Art One of the skin aging phenomena is the reduction of "moisture" and "tension" and the accompanying emphasis on "wrinkles" and "slackness". The origin has not been completely elucidated yet, but the Journal of Cosmetic Technology, 15 , 77 (1981) (English translation: J. Soc. Cosmet. Chem. Japan) and Cell Structure an
d Function, 9 , 357 (1984) and Maria et al. (Carbohydrate Research, 159 , 127-136.
(1987)), the production of glycosaminoglycans such as hyaluronic acid by skin cells decreases with age, which is one of the causes of the decrease in skin water content affecting skin function. Are believed to be present. From this point of view, in order to prevent "wrinkles" and "slackness", along with the method of forming an oil film on the skin surface for the purpose of passively preventing loss due to evaporation of water from the epidermis, Focusing on the water retention of glycosaminoglycans for supplementation, it has been carried out to mix hyaluronic acid derived from fermentation of Streptococcus spp. Into various cosmetics, but these cosmetics apply hyaluronic acid to the skin surface. The hyaluronic acid, which is a polymer, is not absorbed by the skin and only exhibits a moisturizing action due to its hygroscopicity. Therefore, the effect disappears when washed off, and the skin function is not improved from the essence. As a substance that activates the function itself of skin cells at the cellular level and improves the productivity of glycosaminoglycan, which is a moisturizing component, an egg white enzyme hydrolyzate or a fractionated component thereof (JP-A-5-27104).
9) has only been developed.

On the other hand, lysophospholipids alone form very fine micelles in water due to their single-chain structure, and they form fine emulsions in emulsion systems. It is characterized by its emulsion stability and prevention of starch aging (hardening and water separation due to recrystallization of starch molecules), and is used as a modifier for emulsifiers and bread. Report of Uchida et al. (The Journal of Dermatology, 18 , 523-527)
(1991)), lysophosphatidylcholine
When this is applied to the skin surface of hairless rats, it penetrates into the skin, but it has been clarified that it does not cause any damage systematically, and it is highly safe as a cosmetic product. From such a viewpoint, there is a skin external preparation (Japanese Patent Laid-Open No. 63-41411), which focuses on the safe and hypoallergenic and stable emulsifying action of lysophospholipids, but the skin aging preventing action is not mentioned at all. Absent. In addition, there is JP-A-3-161414, which advocates lysophosphatidylglycerol in a cosmetic composition and has a moisturizing effect, but this is also the case when the hygroscopic hyaluronic acid is applied to the skin surface and then washed off. The effect cannot be expected.

[0004]

From the above results, in order to prevent morphological changes of the skin due to aging represented by "moisture" and "tension" and "wrinkles", the moisturizing property is improved. The cell activator that increases the amount of glycosaminoglycan in the skin is effective in activating the skin from the inside. On the other hand, there is a demand for the development of a skin beautifying agent having a higher glycosaminoglycan-producing ability than the active ingredient contained in the aforementioned skin cosmetics. Therefore, an object of the present invention is to provide a skin activating agent having a stronger glycosaminoglycan production promoting action.

[0005]

[Means for Solving the Problems] As a result of continuing the search for a glycosaminoglycan production-promoting substance capable of solving the above-mentioned problems, the present inventors have found that specific lysophospholipids promote prominent glycosaminoglycan production. They found that the compound has an action and is highly safe, and completed the present invention.

That is, the present invention provides a skin activating agent containing a compound represented by the following general formula (I) as an active ingredient.

[0007]

Embedded image

[Wherein M represents H or an alkali metal atom] The compound of the above general formula (I) may be commercially available, or commercially available 1-decanoyl-2-acyl-phosphatidic acid. Can also be obtained by treating phospholipase A2 with phospholipase A2. Or the synthesized one
It is also possible to obtain the above compound by treating -decanoyl-2-acyl-phosphatidic acid with phospholipase A2.

The skin activating agent of the present invention having a glycosaminoglycan production promoting action can be used as a cosmetic such as an antiaging cosmetic for the purpose of keeping the skin taut and preventing wrinkles. For the above applications, in the case of obtaining the glycosaminoglycan production promoting effect of the present invention, the compounding ratio of the above compound is based on the total amount of the skin external preparation or the drug,
0.1 to 10% by weight is preferable. Used in 0.1% by weight
If it is less than 10% by weight, the purpose of promoting the production of glycosaminoglycan cannot be sufficiently exhibited, while if it exceeds 10% by weight, problems such as sticky feeling tend to occur and it is not practical.

The cosmetic containing the skin activating agent of the present invention may be of any type, and in addition to the above-mentioned compounds as active ingredients, various cosmetic ingredients and additives used in ordinary cosmetics, for example, Inorganic pigments, organic pigments, inorganic powders, induced powders, hydrocarbons, silicones, esters, triglycerides, lanolins, waxes, waxes, animal and vegetable oils, surfactants, polyhydric alcohols, sugars, Vitamins, amino acids, antioxidants, preservatives, fragrances, thickeners and the like may be added.

[0011]

EXAMPLES The present invention will be further described below with reference to examples, but it goes without saying that the scope of the present invention is not limited to these examples. Example First, the results of an experiment for evaluating the effect of the compound of the general formula (I) used in the present invention will be shown. Glycosaminoglycan production evaluation by NB1 RGB cells The cells used for glycosaminoglycan production promotion evaluation are
Human neonatal skin fibroblasts NB1 RGB. This cell has been widely used in this type of test, and is suitable as a cell used in the above test. Further, in this test, since cells of human origin are used, it is more appropriate as a drug evaluation method considering application to the human body.

NB1RGB cells were seeded in a culture dish (48 WELL) having a diameter of 1.2 cm at a density of 5 × 10 ⁴ cells / dish and cultured at 37 ° C. for 24 hours using Dulbecco's modified Eagle medium containing 10% fetal bovine serum. . afterwards,
The test compound was added to Dulbecco's modified Eagle medium containing fetal bovine serum at a concentration of 0.5% so that the concentration in the medium was 0.5 to 100 μM. After culturing for 24 hours, the medium was replaced with a new 0.5% bovine serum-containing medium supplemented with the test compound at the same concentration. At this time, 370 KBq / ml of ³ H-glycosamine was added to the medium, and the culture was continued for another 24 hours. After culturing, 2 in 0.1 MTris.HCl (pH 8)
mg pronase was added and incubated at 50 ° C. for 1 hour. Cetylpyridinium chloride was added to a final concentration of 1% in the coexistence of 100 μg hyaluronic acid as a carrier, and the resulting precipitate was centrifuged. The precipitate was centrifugally washed three times with 1 ml of a 1% aqueous cetylpyridinium chloride solution, 0.2 ml of a 0.05% aqueous cetylpyridinium chloride solution containing 0.5 M NaCl was added, and the mixture was vigorously stirred. To this, 5 ml of the emulsion scintillator ACSII was added, and the radioactivity was measured with a liquid scintillation counter, and evaluated based on the control value. The results are shown in Table 1 below together with the control and comparative examples.

[0013]

[Table 1]

Compound 1 1-decanoyl-lysophosphatidic acid Comparative 1 1-decanoyl-lysophosphatidylcholine Comparative 2 lysophosphatidylglycerol Comparative 3 Lysophosphatidic acid derived from soybean phospholipid Next, the cosmetic composition containing the skin activator of the present invention is blended. Examples will be given. Example 1 (Ointment 1) parts by weight A 1-decanoyl-lysophosphatidic acid 1 white petrolatum 25 stearyl alcohol 22 B propylene glycol 12 sodium lauryl sulfate 1.5 preservative / antioxidant proper amount perfume appropriate amount purified water residual amount ── ──────────────────────────────── Total amount 100 A Components belonging to A are melted in a hot water bath (oil phase), separately The components belonging to B are dissolved by heating (aqueous phase). Add the water phase to the oil phase,
The mixture was stirred, emulsified and cooled to obtain an ointment. Example 2 (Ointment 2) parts by weight A 1-decanoyl-lysophosphatidic acid 2 white petrolatum 40 cetanol 18 sesquiolein sansorbitan 5 lauromacrogol 0.5 B preservative / antioxidant appropriate amount fragrance appropriate amount purified water residual amount ─ ───────────────────────────────── Total amount 100 A Components belonging to A are melted in a hot water bath (oil phase), Separately, the components belonging to B are dissolved by heating (aqueous phase). Add the water phase to the oil phase,
The mixture was stirred, emulsified and cooled to obtain an ointment. Example 3 (neutral cream) parts by weight 1-decanoyl-lysophosphatidic acid 2 stearyl alcohol 7 stearic acid 2 hydrogenated lanolin 2 squalene 5 2-octyldodecyl alcohol 6 POE (25) cetyl alcohol ester 3 glycerin monostearate ester 2 Propylene glycol 5 Preservative / antioxidant Appropriate amount Perfume Appropriate amount Purified water Remaining amount ─────────────────────────────────── Total 100 Add propylene glycol to purified water and heat to 70 ℃
Keep (water phase). Mix other ingredients, heat and melt to 70
Keep at ℃ (oil phase). The oil phase was added to the aqueous phase, and the mixture was pre-emulsified and then uniformly emulsified with a homomixer to obtain a neutral cream. Example 4 (Emulsion) parts by weight A 1-decanoyl-lysophosphatidic acid 0.5 Silicone KF56 2 Isopropyl myristate 3 POE (20) POP (4) cetyl ether 1 B Glycerin 3 Hibiswako 105 0.2 Preservative / oxidation Inhibitor Proper amount Perfume Proper amount Purified water Residual amount ────────────────────────────────── Total amount 100 Formulation A and B was melted at 70 ° C., and A was added to B to uniformly emulsify to obtain an emulsion. Example 5 (packing agent) parts by weight 1-decanoyl-lysophosphatidic acid 3 ethyl alcohol 10 glycerin 5 dipropylene glycol 5 polyethylene glycol 4000 1 polyvinyl alcohol 10 vinyl acetate resin emulsion 13 titanium oxide 12 olive oil 3 squalene 0.5 preservative Antioxidant Appropriate amount Perfume Appropriate amount Purified water Remaining amount ─────────────────────────────────── 100 All components are uniform To obtain a pack agent. Example 6 ( Toilet lotion) parts by weight 1-decanoyl-lysophosphatidic acid 0.5 glycerin 4 1,3-butylene glycol 4 ethanol 7 POE (20) oleyl alcohol 0.5 preservative / antioxidant proper amount perfume proper amount purified water Remaining amount ────────────────────────────────── Total amount 100 Purified water, glycerin, 1,3-butylene glycol Dissolve. Separately, 1-decanoyl-lysophosphatidic acid and POE (20) oleyl alcohol were dissolved in ethanol, and this was added to the above aqueous solution to dissolve, and filtered to obtain a lotion.

[0015]

As described above, the present invention provides a novel and remarkable glycosaminoglycan production promoting substance,
A skin-activating external preparation containing this compound as an active ingredient can exhibit an excellent skin beautifying effect.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI technical display area C07F 9/10 B 9155-4H

Claims (3)

[Claims] 1. A skin activator having a glycosaminoglycan production promoting action, which comprises a compound represented by the following general formula (I) as an active ingredient. Embedded image [In the above formula, M represents H or an alkali metal atom] 2. A skin external preparation containing the skin activating agent according to claim 1. 3. A skin anti-aging external preparation containing the skin activator according to claim 1.