JP2983311B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin which contains L-arginine-L-aspartate and DL-.alpha.-tocopherol-L-ascorbic acid phosphoric acid diester and / or a salt thereof to prevent drying of the skin. About.

[0002]

2. Description of the Related Art Conventionally, there have been those containing various moisturizing agents to prevent drying of the skin, and those containing various vitamins and biological extracts to activate aging skin. Nothing that has the same effect has yet been developed.

[0003]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an external preparation for skin having an action of preventing skin from drying and activating the skin. Other objects and features of the present invention will be apparent from the following description.

[0004]

According to the present invention, L-arginine-L-aspartate, DL-α-tocopherol-L-ascorbic acid phosphate diester and / or
Alternatively, there is provided a skin external preparation comprising a salt thereof and a pharmacologically acceptable carrier.

[0005] The present inventors have conducted intensive studies to find out what prevents drying of the skin. As a result, L-arginine-L-aspartate and DL-α-tocopherol-L-ascorbic acid phosphate diester (hereinafter referred to as EPC and (Abbreviation) and / or a salt thereof (hereinafter abbreviated as EPC salt) was found to have an effect of preventing drying, and the present invention was completed.

[0006] L-arginine-L- used in the present invention
Aspartate is a 1: 1 salt with L-aspartic acid synthesized in the same manner as L-arginine biosynthesized by chemical synthesis or microorganisms. L- used in the present invention
The content of arginine-L-aspartate is 0.0001 to 10% by weight, preferably 0.01 to 1% by weight, based on the total amount of the external preparation for skin.
Is desirable.

The EPC or EPC salt used in the present invention comprises vitamin E (DL-α-tocopherol) and vitamin C
(L-ascorbic acid) ester-linked with phosphoric acid. The amount of EPC or EPC salt used in the present invention is preferably 0.0001 to 10% by weight, and more preferably 0.01 to 1% by weight, based on the amount of the external preparation for skin.

As the pharmacologically acceptable carrier to be incorporated in the external preparation for skin of the present invention, any carrier commonly used in external preparations for skin can be used. Examples of the carrier include water, lower alcohols and higher alcohols. , Polyhydric alcohols, monosaccharides,
Disaccharides, polysaccharides, hydrocarbon oils, fats and oils, waxes, fatty acids, silicone oils, nonionic surfactants, ionic surfactants, silicon surfactants, polymer compounds and any of the above Selected aqueous mixtures and emulsified mixtures can be mentioned.

The external preparation for skin of the present invention may further contain, if necessary, various components generally used in cosmetics and pharmaceuticals, such as vitamin oil, retinol, retinol acetate and the like, as long as the effects of the present invention are not impaired. a compound, riboflavin, riboflavin butyrate, vitamin B ₂ such as flavin adenine dinucleotide, pyridoxine hydrochloride,
Vitamin B ₆ such as pyridoxine dioctanoate, L
-Ascorbic acid, L-ascorbic acid dipalmitate, L-ascorbic acid-2-sodium sulfate,
Vitamin Cs such as L-ascorbic acid phosphate;
Pantothenic acids such as calcium pantothenate, D-pantothenyl alcohol, pantothenyl ethyl ether, acetyl pantothenyl ethyl ether, vitamin Ds such as ergocalciphenol, cholecalciferol, nicotinic acid, nicotinamide, benzyl nicotinate and the like Nicotinic acids, α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate, D-succinic acid
Vitamin Es such as L-α-tocopherol, vitamin P, vitamins such as biotin, avocado oil, palm oil,
Peanut oil, beef tallow, rice bran oil, jojoba oil, evening primrose oil, carnauba wax, lanolin, liquid paraffin, squalane, oils such as isostearyl palmitate, isostearyl alcohol, glycerin tri-2-ethylhexanoate, glycerin, sorbitol, polyethylene glycol Moisturizers such as 1,3-butylene glycol, collagen, hyaluronic acid, chondroitin sulfate, sodium dextran sulfate, amyl paradimethylaminobenzoate, octyl methoxycinnamate, 4-tert-butyl-4
-Methoxy-dibenzoylmethane, glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, 2-hydroxy-4-methoxybenzophenone, sodium 2-hydroxy-4-methoxybenzophenone-5-sulfonate, urocanic acid, diisopropyl UV absorbers such as ethyl cinnamate, antioxidants such as sodium erythorbate and parahydroxyanisole, sodium stearyl sulfate, diethanolamine cetyl sulfate, cetyl trimethyl ammonium saccharin, polyethylene glycol isostearate, polyoxyethylene octyl dodecyl alcohol, sorbitan mono Isostearate, polyoxyethylene hydrogenated castor oil, glyceryl arachiate,
Surfactants such as diglycerin diisostearate, phospholipids, preservatives such as methyl paraoxybenzoate, ethyl paraoxybenzoate, and butyl parahydroxybenzoate, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, Anti-inflammatory agents such as allantoin, placental extracts, glutathione, whitening agents such as saxifrage extracts, oubaku, spinach, sicon, peonies, assembly, birch, sage, loquat, carrot, aloe, mallow, iris, grapes, yoquinin, loofah, Extracts of lily, saffron, senkyu, ginger, hypericum, ononis, rosemary, garlic, etc., royal jelly, photosensitizer, cholesterol derivative,
Activators such as calf blood extract, blood circulation promoters such as γ-oryzanol, sulfur, antiseborrheic agents such as thiantol, carboxyvinyl polymers, carboxymethylcellulose, thickeners such as carboxyhydroxypropylcellulose, flavors,
Water, alcohol, coloring agents such as titanium yellow, carthamine, safflower red and the like, resin powders such as polyethylene and nylon and the like can be appropriately compounded as required.

The external preparation for skin of the present invention may have any dosage form, for example, an oily preparation, a solubilizing system for a lotion, an emulsifying system such as a milky lotion or a cream, or an ointment or a powdery dispersion product. be able to.

The amount of the external preparation for skin of the present invention is not particularly limited, but is preferably 1.5 to 2 m / time in a lotion system.
l. Apply 1 to 1.5 ml for emulsions and about 0.2 g for creams twice a day.

[0012]

Next, the present invention will be described in more detail by way of examples. Note that the present invention is not limited by this. The compounding amount is% by weight.

Example 1: Lotion (1) L-arginine-L-aspartate 5.0 (2) DL-α-tocopherol-L-ascorbic acid diester dipotassium phosphate 5.0 (3) tocopherol acetate 0.01 (4) glycerin 4.0 (5) 1,3-butylene glycol 4.0 (6) ethanol 7.0 (7) polyoxyethylene (50 mol) oleyl alcohol ether 0.5 (8) methyl paraben 0.2 (9) citric acid 0.05 (10) sodium citrate 0.1 (11 ) Fragrance 0.05 (12) Purified water residue

(Preparation method) Citric acid, sodium citrate, glycerin, 1,3-butylene glycol, L
-Arginine-L-aspartate and DL-α-tocopherol-L-ascorbic acid diester dipotassium salt were dissolved. Separately, polyoxyethylene oleyl alcohol ether, tocopherol acetate, perfume, and methyl paraben were dissolved in ethanol, added to the above-mentioned purified aqueous solution, 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 mol) sorbitan monopalmitate Ester 2.0 (7) Store phosphoric acid monoglyceride 2.0 (8) Sodium N-stearoyl glutamate 0.5 (9) 2-Hydroxy-4-methoxybenzophenone 1.0 (10) Retinol acetate 2.0 (11) Evening primrose oil 0.05 (12) Flavor 0.03 ( 13) L-arginine-L-aspartate 0.01 (14) DL-α-tocopherol-L-ascorbic acid diester dipotassium phosphate 1.0 (15) 1,3-butylene glycol 5.0 (16) Polyethylene glycol 1500 5.0 (17 ) Purified water residue

(Production method) Ingredients (1) (2) (3) (4) (5) (6) (7) (8)
(9) (10) (11) (12) was dissolved by heating and heated to 75 ° C.
3) It was added to (14), (15), (16) and (17) with stirring. After homogenizing the emulsion to make the emulsified particles fine, the mixture was rapidly cooled while stirring to obtain a cream.

Example 3: Emulsion (1) Stearic acid 1.5 (2) Cetyl alcohol 0.5 (3) Beeswax 2.0 (4) Polyoxyethylene (10 mol) monooleate 1.0 (5) Octyl methoxycinnamate 2.0 (6) ) DL-α-tocopherol-L-ascorbic acid diester phosphate dipotassium salt 0.2 (7) L-arginine-L-aspartate 1.0 (8) Sodium hyaluronate 0.1 (9) Triethanolamine 0.75 (10) Glycerin 7.0 ( 11) Ethanol 3.0 (12) Ethyl paraben 0.3 (13) Fragrance 0.03 (14) Purified water residue

(Preparation method) A perfume was added to ethanol and dissolved (alcohol phase). Glycerin, triethanolamine, sodium hyaluronate, DL-α-tocopherol-L-ascorbic acid diester dipotassium phosphate dipotassium phosphate and L-arginine-L-aspartate were added to purified water, dissolved and kept at 70 ° C. phase). The other components were mixed, dissolved by heating and kept at 70 ° C. (oil phase). Preliminary emulsification was performed by adding the oil phase to the water phase, and the mixture was uniformly emulsified with a homomixer. The alcohol phase is added to this with stirring. Thereafter, the mixture was cooled to 30 ° C. with stirring to obtain an emulsion.

Example 4: Foam mask (1) L-arginine-L-aspartate 0.5 (2) DL-α-tocopherol-L-ascorbic acid disodium phosphate disodium salt 0.01 (3) 1,3-butylene glycol 5.0 (4) Glycerin 7.0 (5) Methylparaben 0.1 (6) Potassium hydroxide 0.15 (7) Stearic acid 0.5 (8) Myristic acid 1.0 (9) Bacyl alcohol 1.5 (10) Polyoxyethylene (60 mol) hydrogenated castor oil 3.0 (11) Fragrance 0.05 (12) Liquefied petroleum gas 6.0 (13) Dimethyl ether 3.0 (14) Purified water residue

(Preparation method) Ingredient (1) (2) (3) (4) (5)
(6) is added and dissolved by heating at 70 ° C., and the components (7), (8), and (9) are contained therein.
(10) A solution obtained by heating and dissolving (11) at 75 ° C. was added, and the mixture was sufficiently stirred and then cooled. This is filled in a container and the last component (12)
(13) was filled as a propellant to obtain a foam mask.

Example 5: Ointment (1) L-arginine-L-aspartate 0.5 (2) DL-α-tocopherol-L-ascorbic acid diester dipotassium phosphate 0.5 (3) Tocopherol acetate 1.0 (4) Palmitic acid Retinol 0.5 (5) Stearyl alcohol 18.0 (6) Mokuro 20.0 (7) Polyoxyethylene (20 mol) monooleate 0.25 (8) Glycerin monostearate 0.3 (9) Vaseline 40.0 (10) Purified water residue

(Preparation method) L-arginine-L-aspartate and DL-α-tocopherol-L-ascorbic acid diester dipotassium phosphate were added to purified water, dissolved and maintained at 70 ° C. (aqueous phase). The remaining components were mixed and dissolved at 70 ° C. (oil phase). The oil phase was added to the aqueous phase, uniformly emulsified by a homomixer and then cooled to obtain an ointment.

Evaluation Example 1 The moisturizing ability of L-arginine-L-aspartate and EPC was evaluated by calculating a water evaporation rate constant.
That is, a 10% aqueous solution of L-arginine-L-aspartate or EPC, and a 1: 1 mixture thereof were dropped on filter paper, and the weight change was measured over time using a precision balance and a personal computer. The water evaporation rate constant was calculated. The results are shown in Table 1. The smaller this value is, the less the moisture evaporates and the more moisturizing effect is.

[0024]

[Table 1]

From the above results, it was found that L-arginine-L-aspartate and EPC have a moisturizing ability, and when they are combined, the moisturizing effect is further enhanced.

Evaluation Example 2 A three-week continuous test was performed on a woman with dry skin using the cream formulation of Example 2. Then, the moisturizing effects of L-arginine-L-aspartate and EPC on the skin were evaluated by using the water content in the skin stratum corneum before and after continuous application as an index of electrical conductivity. The results are shown in Table 2. As shown in Table 2, the higher the electrical conductivity, the greater the water content in the stratum corneum.

[0027]

[Table 2]

From the above results, it was confirmed that L-arginine-L-aspartate and EPC have a high moisturizing effect on skin even in a product system.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 31/00 617 A61K 31/00 617J 31/195 31/195 31/665 31/665 (72) Inventor Kamaru Kumano Kanagawa Prefecture 1050 Nippa-cho, Kohoku-ku, Yokohama-shi Shiseido Research Laboratories Co., Ltd. (56) References JP-A-59-219295 (JP, A) WO 92/6667 (WO, A1) WO 92/7544 (WO, A1) (58) A) Surveyed field (Int.Cl. ⁶ , DB name) A61K 7/00 A61K 7/48 A61K 31/195 A61K 31/665

Claims (3)

(57) [Claims] 1. A skin comprising L-arginine-L-aspartate, DL-α-tocopherol-L-ascorbic acid phosphate diester and / or a salt thereof, and a pharmacologically acceptable carrier. External preparation. 2. The external preparation for skin according to claim 1, wherein the content of L-arginine-L-aspartate is 0.0001 to 10% by weight. 3. The content of DL-α-tocopherol-L-ascorbic acid phosphoric acid diester and / or a salt thereof,
The external preparation for skin according to claim 1, wherein the amount is 0.0001 to 10% by weight.