JP2851701B2 - External preparation for skin - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an external preparation for skin, particularly to an improvement in external preparation for skin which prevents aging of the skin.

[Background Art] As the skin ages, the epidermis becomes thinner, causing symptoms such as a decrease in keratin production.

As a cause of such skin aging, age is also an important factor from a macro perspective, but more direct causes are drying, oxidation by active oxygen, etc., and damage by ultraviolet rays (especially in the UV-A region. To the skin dermis).

Conventionally, various measures have been taken to prevent such aging of the skin, and a skin external preparation containing various moisturizing agents to prevent aging of the skin due to drying, and aging of the skin due to oxidation. External preparations containing an antioxidant such as vitamin E for prevention, and external preparations containing an ultraviolet absorber for preventing skin aging due to ultraviolet rays have been used.

However, the conventional means for preventing skin aging cannot leave the area of coping treatment, and cannot obtain a sufficient effect of preventing skin aging.

[Disclosure of the Invention] The present invention has been made in view of the problems of the related art, and an object of the present invention is to provide a skin external preparation that can more efficiently prevent skin aging.

As a result of intensive studies by the present inventors to achieve the above object, the present inventors have found that it is possible to obtain an extremely excellent anti-aging effect on the skin by combining a specific tocopherol derivative and an ultraviolet absorber, thereby completing the present invention. Reached.

That is, the cross-linking of collagen in the skin increases with aging (Cutaneous Aging Edited by Albert M. Kli
gman and Yoshio Takase UNIVERSITY OF TOKYO PRESS, 2
63-274, 1988; Sugiyama T., Fujimoto D., Arai C., and H
asegawa M., Biomed. Res. 8: 349-351, 1987).

On the other hand, collagen is cross-linked by ultraviolet rays (Fujimori
E., FEBS Lett 235 (1-2) 98-102, 1988).

Therefore, the present inventors have decided to prevent aging of the skin by preventing cross-linking of collagen in the skin.

That is, the external preparation for skin according to claim 1 of the present application is DL-
An external preparation for skin characterized by comprising α-tocopherol 2-L-ascorbic acid diester and / or a salt thereof in an amount of 0.005 to 0.2% by weight and one or more ultraviolet absorbers in an amount of 0.01 to 15.0% by weight. is there.

 Hereinafter, the configuration of the present invention will be described in detail.

DL-α-tocopherol 2-L used in the present invention
-Ascorbic acid phosphoric acid diester (hereinafter abbreviated as EPC)
Or a salt thereof, the preferred amount in the skin external preparation is 0.005 to
0.2% by weight.

As the salt of EPC, alkali metal salts such as sodium and potassium, and alkaline earth metal salts such as calcium and magnesium (abbreviated as EPC-Na or the like) are preferable.

When the amount of EPC is less than 0.005%, a sufficient effect of preventing skin aging may not be obtained. Further, even if it is added in excess of 0.2%, the effect of preventing skin aging is often not enhanced.

In the present invention, one or more ultraviolet absorbers are blended in addition to the EPC or the salt of EPC.

As the ultraviolet absorber used in the present invention, an ultraviolet absorber acceptable as a component of ordinary cosmetics or the like can be appropriately used. For example, 2-ethoxyethyl paramethoxycinnamate, isopropyl paramethoxycinnamate, diisopropylcinnamate, ethylhexyl paramethoxycinnamate, glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, methoxysilicate Cinnamic acid ultraviolet absorbers such as octyl cinnamate, benzoylmethane ultraviolet absorbers such as butylmethoxybenzoylmethane and 4-tert-butyl-4'-methoxy-dibenzoylmethane, glyceryl-mono-2-ethylhexanoyl -Di-paramethoxybenzophenone, 2-2'-dihydroxy-
4-methoxybenzophenone, 2,2'-dihydroxy4,
4'-dimethoxybenzophenone, 2-hydroxy-4
Benzophenone ultraviolet absorbers such as -methoxybenzophenone, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, and benzols such as methyl orthoaminobenzoate, 2-ethylhexyl paradimethylaminobenzoate and octyl paradimethylaminobenzoate. Acid-based UV absorber, glyceryl para-aminobenzoate, amyl-para-
Benzoate UV absorbers such as dimethylaminobenzoate and ethyl-4-bishydroxypropylaminobenzoate, 2-ethylhexyl-2-cyano-3,3'-diphenylacrylate, digalloyltrioleate, salicylic acid-2-ethylhexyl, and homomethyl salicylate And other ultraviolet absorbers such as guaiazulene and urocanic acid.

The amount of the ultraviolet absorbent in the present invention varies depending on the type of the ultraviolet absorbent, but is generally 0.01 to 15.0% by weight based on the total amount of the external preparation for skin.

If the amount of the ultraviolet absorber is less than 0.01%, the synergistic effect with EPC may not be sufficient. In addition, even if the content is more than 15.0%, the effect of preventing skin aging is often not enhanced.

The external preparation for skin of the present invention includes, in addition to the above essential components, other components used in external cosmetic preparations such as ordinary cosmetics, pharmaceuticals, and quasi-drugs, for example, vitamin A oil, retinol, and vitamin A such as retinol acetate. s, Ribofurabon, vitamin B ₂ such as riboflavin butyrate, flavin adenine dinucleotide, pyridoxine hydrochloride, vitamin B ₆ such as pyridoxine dioctanoate, L- ascorbic acid, L- ascorbic acid dipalmitate ester, L- Vitamin Cs such as sodium ascorbic acid-2-sulfate, pantothenic acids such as calcium pantothenate, D-pantothenyl alcohol, pantothenyl ethyl ether, and acetyl pantothenyl ethyl ether; vitamin Ds such as ergocalciferol and cholecalciferol , Nicotinic acid, nicotinamide, nicotine Nicotine acids such as benzyl, alpha-
Tocopherol, tocopherol acetate, nicotinic acid DL-
Vitamin Es such as α-tocopherol and D-α-tocopherol succinate; vitamins such as vitamin P and biotin; glycine, alanine, valine, leucine, isoleucine, serine, trionine, aspartic acid and salts thereof, glutamic acid and salts thereof , Lysine, arginine, cysteine, cystine, methionine, phenylalanine,
Tyrosine, histidine, tryptophan, proline, N
N-acyl acidic amino acid salts such as -palmitoyl L-diethyl aspartate, N-coconut fatty acid-sodium L-glutamate, acyl neutral amino acid salts such as coconut fatty acid sarcosine triethanolamine, sodium lauroylmethyl-β-alanine, Pyrrolidone carboxylic acid and its salt, POE (40) hydrogenated castor oil monopyroglutamic acid monoisostearate diester, coconut oil fatty acid-L-
Amino acids and amino acid derivatives such as arginine ethyl ester-DL-pyrrolidone carboxylate, avocado oil, palm oil, peanut oil, tallow, rice bran oil, jojoba oil, evening primrose oil, carnauba wax, lanolin, liquid paraffin,
Oils such as squalane, isostearyl palmitate, isostearyl alcohol, glycerin tri-2-ethylhexanoate, glycerin, sorbitol, polyethylene glycol, 1,3-butylene glycol, collagen,
Moisturizing agents such as hyaluronic acid, chondroitin sulfate, dextran sulfate sodium, etc .; antioxidants such as sodium erysorbate, parahydroxyanisole; sodium stearyl sulfate, diethanolamine cetyl sulfate, cetyl trimethyl ammonium saccharin, polyethylene glycol isostearate, glyceryl arachiate Glycerin diisostearate, surfactants such as phospholipids, preservatives such as ethylparaben, butylparaben, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, anti-inflammatory agents such as allantoin, placenta extract, Glutathione, a whitening agent such as a saxifrage extract, oak, oak, sicon, peony, assembly, birch, sage, loquat, carrot, aloe, mallow, Activators such as extracts of iris, grape, yokuinin, loofah, lily, saffron, senkyu, ginger, hypericum, ononis, rosemary, garlic, royal jelly, photosensitizer, cholesterol derivative, calf blood extract, etc. Blood circulation promoters such as oryzanol, antiseborrheic agents such as sulfur and thianthol, thickeners such as carboxyvinyl polymer, carboxymethylcellulose, carboxyhydroxypropylcellulose, flavors, water, alcohol, titanium yellow, carmine, and safflower red. An agent, a resin powder such as polyethylene and nylon, and the like can be appropriately compounded as necessary.

The dosage form of the external preparation for skin of the present invention is arbitrary. For example, the dosage form may be a solubilizing agent such as a lotion, an emulsified system such as an emulsion or a cream, or an ointment, a dispersant, or an aerosol.

BEST MODE FOR CARRYING OUT THE INVENTION Next, the present invention will be described in more detail with reference to examples.
The present invention is not limited to the embodiments.

Effect of Preventing Crosslinking of Collagen by Ultraviolet Light First, a method of determining the rate of crosslinking of collagen by ultraviolet light will be described.

Collagen was extracted from human placenta by pepsin treatment and purified by salting out (Nishihara T., and Miyata
T., Collagen Symposium 366-93, 1962).

Then, electrophoresis (Hayashi T., and Nagai Y., J. Bi
ochem., 86 (2), 453-459, 1979), and the purity of the collagen was measured to be 94%. Extracted and purified collagen (final concentration 1 mg / ml) was added to phosphate buffer pH 7.4 at 37 ° C.
℃ to form collagen fibers, then
Ultraviolet rays (TOSHIBA FL20S.BLB lamp, UV-A region, peak 365 nm) with an energy of 7.0 J / cm ² were irradiated. During irradiation, various samples shown in Tables 1 and 2 described below were allowed to coexist with collagen.

Each sample was prepared using EPC-
K and sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate as an ultraviolet absorber were added in the amounts shown in the respective tables.

The ratio of the crosslinked collagen in the irradiated collagen was measured by an electrophoresis method and a densitometer (Densitometer F-808 for fluorescence manufactured by Cosmo).

Then, the inhibition rate of collagen crosslinking was determined from the following equation.

Next, the experimental results are shown.

As is apparent from Table 1, it is preferable to mix EPC in an amount of 0.005 to 0.2% by weight. If the EPC is less than 0.005% by weight, an appropriate synergistic effect cannot be obtained. No enhancement of the effect is observed.

As is apparent from Table 2, the blending amount of the ultraviolet absorber is preferably 0.01 to 15.0% by weight, and if less than 0.01% by weight, no synergistic effect with EPC is observed. No increase in the effect is observed even if it is added in excess.

As a result, EPC or an ultraviolet absorber alone cannot efficiently suppress the crosslinking of collagen.

In addition, in the case of other ascorbic acid or a derivative thereof or a combination of tocopherol and an ultraviolet absorber, the excellent collagen crosslinking inhibitory effect as described above was not observed.

As is clear from Tables 3 to 5, ascorbic acid or tocopherol alone has no synergistic effect on the collagen crosslinking inhibitory effect, and no synergistic effect is observed on ascorbic acid derivatives such as ascorbic acid phosphate.

Thus, it is understood that the collagen crosslinking inhibitory action is enhanced by the specific synergistic action of EPC and the ultraviolet absorber.

Next, the actual effect of preventing skin aging was examined using hairless mice.

3 groups of 3 9-week-old hairless mice (A, B, C groups)
And irradiated with ultraviolet light (14 J / cm ² / day) using a Toshiba 32BL lamp for 12 weeks. The sample should be 0.
1 ml / animal was applied. 10 days after the end of irradiation, cut off 3 g of skin,
After homogenizing in 3% acetic acid and incubating overnight, it was centrifuged (2000 rpm for 10 min). 5 for sediment
% Trichloroacetic acid, and acid hydrolyze at 90 ° C. for 30 minutes. After centrifugation (2000 rpm for 10 min), the supernatant was dialyzed and the amount of hydroxyproline in the collagen was determined using Stagemann and Stald.
er method (H. Stagemann and K. Stalder Clinica Chimic
a Acta, 19, 267-273, 1967), and the amount of cross-linked collagen was calculated.

 The sample liquid is as follows.

Basic formula Weight% Citric acid 0.02 Sodium citrate 0.08 Glycerin 5.0 Ethanol 5.0 Methyl parahydroxybenzoate 0.1 Purified water Residue Group A (control)… Basic formula Group B (Example)… Basic formula + EPC (0.2%) + 2-hydroxy4 -Methoxybenzophenone 5-sodium sulfonate (1%) Group C (Comparative Example) Basic formula + diisostearic acid L-
Ascorbin (1%) + 2-hydroxy-4-methoxybenzophenone 5-sodium sulfonate (1%) The method for calculating the collagen crosslinking inhibition rate is as described above.

 The results are shown in the following Table-6.

Next, specific formulation examples of the present invention are shown. The content is% by weight
Indicated by In addition, the products according to each of the following examples also had an effect of suppressing collagen crosslinking, and exhibited an excellent effect of preventing skin aging in actual use.

Example 1 Lotion (1) EPC 0.05 (2) Sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate 0.1 (3) Tocopherol acetate 0.01 (4) Glycerin 4.0 (5) 1,3-butylene glycol 4.0 ( 6) Ethanol 8.0 (7) Polyoxyethylene (60) hydrogenated castor oil 0.5 (8) Methyl paraben 0.2 (9) Citric acid 0.05 (10) Sodium citrate 0.1 (11) Perfume 0.05 (12) Purified water Residue <Production method> EPC, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, citric acid, sodium citrate, glycerin, and 1,3-butylene glycol are dissolved in purified water. Separately, polyoxyethylene (60) in ethanol
Hydrogenated castor oil, tocopherol acetate, fragrance, and methylparaben were dissolved, added to the purified aqueous solution described above, solubilized, and filtered to obtain a lotion.

Example 2 Cream (1) cetostearyl alcohol 3.5 (2) squalane 40.0 (3) beeswax 3.0 (4) reduced lanolin 5.0 (5) ethyl paraben 0.3 (6) polyoxyethylene (20) sorbitan monopalmitate 2.0 (7) ) Stearic acid monoglyceride 2.0 (8) Sodium N-stearoylglutamate 0.5 (9) 2-Hydroxy-4-methoxybenzophenone 0.5 (10) Octyl methoxycinnamate 1.0 (11) Retinol acetate 2.0 (12) Evening primrose oil 0.05 (13) Perfume 0.03 (14) EPC-Na 0.1 (15) 1,3-butylene glycol 5.0 (16) Polyethylene glycol 1500 5.0 (17) Purified water residue <Production method> Cetostearyl alcohol, squalane, beeswax,
Heat reduced lanolin, ethyl paraben, polyoxyethylene (20) sorbitan monopalmitate, monoglyceride stearate, sodium N-stearoylglutamate, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, retinol acetate, evening primrose oil EPC-Na, 1,3 dissolved and separately heated to 75 ° C
Add with stirring to purified water with butylene glycol, polyethylene glycol 1500. After homogenizing the mixture to make the emulsified particles fine, the mixture was rapidly cooled while stirring to obtain a cream.

Example 3 Emulsion (1) EPC-Mg 0.2 (2) 2-Ethylhexyl paradimethylaminobenzoate 0.1 (3) Mono-2-ethylhexyl diparamethoxycinnamate 0.2 (4) Stearic acid 1.5 (5) Cetyl alcohol 0.5 (6) Beeswax 2.0 (7) Polyoxyethylene (10) monooleate 2.0 (8) L-arginine 0.3 (9) Na-glutamate 0.02 (10) PCA-Na 0.05 (11) Na-hyaluronate 0.01 (12 ) Propylene glycol 5.0 (13) Glycerin 3.0 (14) Ethanol 3.0 (15) Ethyl paraben 0.3 (16) Fragrance 0.03 (17) Carboxyvinyl polymer 0.12 (18) Purified water residue <Production method> Add perfume to ethanol and dissolve (Alcohol phase). EPC-Mg, L-arginine, sodium L-glutamate, PCA-Na, sodium hyaluronate, propylene glycol, glycerin, and carboxyvinyl polymer are added to purified water, and the mixture is dissolved by heating and maintained at 70 ° C. (aqueous phase). Mix other components, heat and maintain at 70 ° C (oil phase). Preliminary emulsification is performed by adding the oil phase to the water phase, and the mixture is uniformly emulsified with a homomixer. The alcohol phase is added while stirring this. Thereafter, the mixture was cooled to 30 ° C. with stirring to obtain an emulsion.

Example 4 Foam Mask (1) EPC-K 0.02 (2) 4-tert-butyl-4'-methoxy-dibenzoylmethane 0.5 (3) Stearic acid 1.0 (4) Behenylic acid 1.0 (5) Self-emulsifying monostearin Glycerin acid 1.5 (6) Polyoxyethylene monostearate (5) Glycerin 2.5 (7) Bacyl alcohol 1.5 (8) Fragrance 0.05 (9) Glycerin 5.0 (10) 1,3-butylene glycol 5.0 (11) Polyethylene glycol 1500 3.0 (12) Methyl paraben 0.1 (13) Potassium hydroxide 0.15 (14) Purified water residue (15) Liquefied petroleum gas 6.0 (16) Dimethyl ether 2.0 <Production method> EPC-K, glycerin, 1,3-butylene glycol, Polyethylene glycol 1500, methyl paraben,
Add potassium hydroxide and heat to 70 ° C to dissolve. The other components except for liquefied petroleum gas and dimethyl ether are dissolved by heating and added. The resulting mixture is filled into a container. Finally, liquefied petroleum gas and dimethyl ether were added as propellants to obtain a foam mask.

Example 5 Ointment (1) EPC-Ca 0.1 (2) Octyl 4.0 paradimethylaminobenzoate (3) Butylmethoxybenzoylmethane 4.0 (4) Tocopherol acetate 0.5 (5) Retinol paramitate 1.0 (6) Stearyl alcohol 18.0 (7) ) Mokuro 20.0 (8) Polyoxyethylene (10) monooleate 0.25 (9) Glycerin monostearate 0.3 (10) Vaseline 32.0 (11) Purified water residue <Production method> EPC-Ca was added to purified water. C. (aqueous phase), and other components are mixed and dissolved at 70.degree. C. (oil phase). The oil phase was added to the water phase, and the mixture was uniformly emulsified with a homomixer and then cooled to obtain an ointment.

As described above, according to the external preparation for skin according to the present invention, 0.005 to 0.2% by weight of DL-α-tocopherol 2-L-ascorbic acid diester and / or a salt thereof and one or more ultraviolet absorbers 0.01 -15.0% by weight, so that collagen cross-linking can be prevented and an excellent skin aging preventing effect can be obtained.

──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-59-219295 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 7/00-7/50 A61K 31 / 375

Claims (1)

(57) [Claims] 1. A diester of DL-α-tocopherol 2-L-ascorbic acid phosphate and / or a salt thereof 0.005 to 0.2.
Wt% and one or more UV absorbers 0.01 to 15.0
% By weight of a skin external preparation.