JP3034077B2 - Melanin-suppressing patch - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention contains kojic acid as an active ingredient.
The present invention relates to a novel melanin-suppressing patch having an effect of preventing pigmentation of melanin such as buckwheat.

[0002]

2. Description of the Related Art Kojic acid is already known as a substance that suppresses melanin production. Its effect is to suppress the activity of the tyrosinase enzyme that converts tyrosine to dopa and dopa to dopaquinone at the initial stage of melanin production. And a fair-skin cosmetic containing this is disclosed in JP-A-53-353.
No. 8 and JP-B-56-18569.
JP-A-62-178506 only discloses a mud-type poultice based on glycerin or polyvinyl alcohol as a main base.

[0003]

The known muddy cataplasm containing kojic acid has a disadvantage that it is unstable to light and is colored with time. Moreover, there is no solution to physical aspects such as kojic acid release, water retention, adhesiveness, sagging / softening of the plaster and skin irritation. Therefore, the patch of the present invention aims to solve these problems.

The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and found that hydrogen sulfite was used to prevent the coloration of kojic acid.
It has been found that sodium or sodium pyrosulfite has a remarkable effect when used in combination with a chelating agent. In addition, the release of kojic acid, water retention, adhesiveness, by combining a main base consisting of a thickener, a wetting agent, and water as an adhesive base
It has been found that problems such as dripping and softening of the plaster and irritation to the skin can be solved. That is, kojic acid, sulfurous acid
The present invention has been completed by making a patch containing sodium hydrogen oxyacid or sodium pyrosulfite , a chelating agent, a thickener, a wetting agent and water as essential components.

Hereinafter, the composition of the patch of the present invention and the compounding ratio thereof will be described. The present invention relates to kojic acid 0.0
1 to 10% by weight, sodium bisulfite or pyrosulfite
Sodium 0.01-5% by weight, chelating agent 0.01-
A melanin-suppressing patch comprising 5% by weight, 5 to 30% by weight of a thickener, 10 to 70% by weight of a wetting agent, and 10 to 70% by weight of water.

More specifically, kojic acid which is an active ingredient of the present invention is 5-hydroxy-2-hydroxymethyl-4-pyrone, and the amount of kojic acid is 0.1%.
It is from 0.01 to 10% by weight, preferably from 0.05 to 5% by weight.

[0007] Sodium bisulfite or pyrosulfite
Sodium acid is used as an antioxidant in an amount of 0.01 to 5% by weight, preferably 0.05 to 3% by weight.

The chelating agent is ethylenediaminetetraacetic acid or a salt thereof, for example, sodium salt, potassium salt, lithium salt, ammonium salt, calcium salt, magnesium salt,
Barium salts and the like are suitable, and at least one of them is incorporated in an amount of 0.01 to 5% by weight, preferably 0.05 to 3% by weight.

Examples of the thickener include synthetic or natural polymer polyacrylate, polyacrylic acid, carboxyvinyl polymer, polyvinyl alcohol, polyvinylpyrrolidone, methoxyethylene maleic anhydride copolymer, sodium carboxymethylcellulose, hydroxypropylcellulose, One or more kinds are selected from methylcellulose, sodium alginate, gelatin and the like, and the compounding amount is 5 to 30% by weight, preferably 5 to 20% by weight.

As the humectant, one or more polyhydric alcohols such as glycerin, ethylene glycol, propylene glycol, isoprene glycol, 1.3-butylene glycol, sorbitol, polyethylene glycol, and polypropylene glycol are selected. The amount is between 10 and 70% by weight, preferably between 20 and 60% by weight.

The water content is 10-70% by weight, preferably 20-60% by weight. Further, in addition to the above essential components, the following additives or drug components can be added as required.

Tackifiers such as polybutene, natural latex, vinyl acetate emulsion and polyacrylate emulsion.

Fillers such as kaolin, zinc white, titanium, talc, bentonite and hydrous aluminum silicate.

Citric acid, acetic acid, malic acid, salicylic acid,
PH adjusters such as succinic acid. Thymol, methyl paraben,
Preservatives such as ethyl paraben and Freside. Solubilizing agents such as crotamiton, peppermint oil, glycol salicylate, benzyl alcohol, isopropyl adipate and polyethylene glycol.

L-menthol, camphor, vitamin E,
Medicinal aids such as turpentine, glycyrrhizic acid and glycyrrhetinic acid. Emulsifiers such as sorbitan fatty acid ester, glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene alkyl ether;

Phenyl salicylate, glycol salicylate, methyl paraaminobenzoate, 2-hydroxy-4-
Methoxybenzophenone, 2,2'-dihydroxy-4,4'-
UV absorbers such as dimethoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid.

Antioxidants such as dibutylhydroxytoluene, butylhydroxyanisole, and gallic esters (ethyl, propyl, octyl).

Alkaline earth metals such as calcium chloride, calcium carbonate and magnesium chloride; aluminum compounds such as potassium lime ban, ammonia lime ban and aluminum hydroxide; aldehydes such as formalin, glyoxal, glutaraldehyde, dialdehyde starch, epoxy Crosslinking agents such as compounds and isocyanate compounds.

The properties of the patch can be further improved by blending one or more of these components.

The patch of the present invention is made uniform by, for example, mixing and dissolving (A) kojic acid with a solubilizer as needed. Next, (B) a chelating agent, sodium bisulfite or
Sodium pyrosulfite and a thickener are mixed and dispersed in a wetting agent and water, and a filler is added to make a uniform kneaded product. Next, (A) is added to (B) to obtain a mixed and uniform kneaded product. This kneaded product is spread on a support by an ordinary method, and then a release coating is stuck thereon and cut into a predetermined size to obtain a product. The support can be appropriately selected from non-stretchable or stretchable woven fabric, knitted fabric, nonwoven fabric, non-woven paper, and the like, and the release coating can be appropriately selected from plastic films such as polyethylene, polypropylene, or polyester and release paper.

[0021]

The patch of the present invention has the following excellent features. a) It can be easily attached to the application site without soiling the hands and clothes. b) The patch itself has excellent shape retention properties and does not have sagging, softening or stickiness. c) Good adhesion to skin. d) Excellent drug release from the base. e) Excellent drug efficacy. f) Less irritating to the skin. g) The base and medicinal ingredients are stable without being affected by aging, and do not discolor. h) Excellent water retention and good cooling action.

Thus, the patch containing kojic acid of the present invention is suggested to be useful as a melanin-suppressing preparation having an excellent action. Among the above, particularly for g), by adding sodium bisulfite or sodium pyrosulfite which is an antioxidant, coloring caused by decomposition of chemically unstable kojic acid due to aging is remarkably improved. In addition, the compounding of ethylenediaminetetraacetic acid or a salt thereof, which is a chelating agent, is performed by supplementing metal ions mixed from water, raw materials, manufacturing equipment, and the like to be used.
It significantly prevents the chelation of kojic acid and eliminates brown spots on the product.

[0023]

Next, the present invention will be described in more detail with reference to examples and test examples.

Example 1 Purified water 43 parts, sorbitol 10 parts, gelatin 5 parts, polyvinyl alcohol 3 parts, ethylenediaminetetraacetic acid 0.1 part
5 parts, 0.5 parts of sodium bisulfite and 3 parts of titanium are placed in a mixer and dissolved at about 50 to 60 ° C. to obtain a uniform dispersion. An aqueous solution of 1 part of kojic acid and 10 parts of purified water is added and mixed. Next, a previously prepared dispersion of 20 parts of glycerin and 4 parts of sodium polyacrylate is charged and stirred and mixed to obtain a uniform kneaded product. This was applied to a thickness of about 400 μm on a nonwoven fabric using a spreader, and then covered with a polyester film, and cut into a desired size to obtain a patch.

Example 2 42 parts of purified water, 8 parts of gelatin, polyvinylpyrrolidone 1
Parts, 0.5 parts of ethylenediaminetetraacetic acid, 0.5 parts of sodium pyrosulfite, and 3 parts of titanium in a mixing machine,
Dissolve at ~ 60 ° C to obtain a uniform dispersion. An aqueous solution of 1 part of kojic acid and 10 parts of purified water is added and mixed. Next, a previously prepared dispersion of 30 parts of glycerin, 3 parts of sodium polyacrylate, and 1 part of sodium carboxymethylcellulose is charged and stirred and mixed to obtain a uniform kneaded product. This is spread on a nonwoven fabric using a spreading machine to a thickness of about 400
μ, then cover with polypropylene film,
The patch was cut into a desired size to obtain a patch.

Example 3 37.4 parts of purified water, 10 parts of sorbitol, gelatin 7
Parts, 2 parts of polyvinyl alcohol, 0.1 part of ethylenediaminetetraacetic acid, 0.5 part of sodium bisulfite, and 10 parts of kaolin are placed in a mixer and dissolved at about 50 to 60 ° C. to obtain a uniform dispersion. 1 part of kojic acid and 10 parts of purified water
Add and mix one part of the aqueous solution. Next, a previously prepared dispersion of 20 parts of glycerin and 2 parts of sodium carboxymethylcellulose is charged and stirred and mixed to obtain a uniform kneaded product. This is spread on a nonwoven fabric using a spreading machine to a thickness of about 400
μ, and then covered with a polyester film, cut into a desired size, and used as a patch.

Example 4 34.5 parts of purified water, 3 parts of polyvinyl alcohol, 0.5 part of ethylenediaminetetraacetic acid, sodium pyrosulfite 1
Parts and 2 parts of titanium are placed in a mixer and dissolved at about 50 to 60 ° C. to obtain a uniform dispersion. An aqueous solution of 1 part of kojic acid and 10 parts of purified water is added and mixed. Next, 30 parts of glycerin, 10 parts of sodium polyacrylate, sodium carboxymethyl cellulose 2
Parts of the dispersion were charged. Further, after adding a dispersion of 10 parts of glycerin and 1 part of polyacrylic acid, the mixture is stirred and mixed to obtain a uniform kneaded product. This is spread on a nonwoven fabric using a spreading machine to a thickness of about 4
It was then coated with a polyester film, and then cut into a desired size to obtain a patch.

Example 5 40.5 parts of purified water, 5 parts of gelatin, 2 parts of polyvinylpyrrolidone, 0.2 parts of ethylenediaminetetraacetic acid, 0.3 parts of sodium bisulfite, and 5 parts of titanium were placed in a mixing machine, and the mixture was heated to about 50 to 50 parts. Dissolve at 60 ° C. to obtain a uniform dispersion. A solution of 1 part of kojic acid, 2 parts of peppermint oil and 1 part of an emulsifier: polyethylene glycol fatty acid ester (MYS-10: manufactured by Nikko Chemicals) is added and mixed. Next, a previously prepared dispersion of 40 parts of glycerin and 3 parts of sodium polyacrylate is charged and mixed with stirring to obtain a uniform kneaded product. This was applied on a nonwoven fabric to a thickness of about 400 μm using a spreader, and then covered with a polypropylene film, and cut into a desired size to obtain a patch.

Example 6 40.8 parts of purified water, 3 parts of polyvinyl alcohol, 4 parts of polyvinylpyrrolidone, 1 part of disodium salt of ethylenediaminetetraacetic acid, 1 part of sodium pyrosulfite, and 10 parts of kaolin were placed in a mixing machine. A dispersion liquid which is dissolved and uniform at 50 to 60 ° C. is obtained. A solution of 1 part of kojic acid, 1 part of crotamiton, and 1 part of an emulsifier: polyethylene glycol fatty acid ester (MYS-10: manufactured by Nikko Chemicals) is added and mixed. Next, a previously prepared dispersion of 20 parts of glycerin, 5 parts of sodium polyacrylate, and 2 parts of sodium carboxymethylcellulose was charged. Further, after adding a dispersion of 10 parts of glycerin and 1 part of polyacrylic acid, the mixture is stirred and mixed to obtain a uniform kneaded product. This was applied on a nonwoven fabric to a thickness of about 400 μm using a spreader, and then covered with a polypropylene film, and cut into a desired size to obtain a patch.

Comparative Example 1 A patch was prepared in the same manner as in Example 1 except that sodium bisulfite 0.5 was omitted.

COMPARATIVE EXAMPLE 2 In the formulation of Example 1, 0.5 of ethylenediaminetetraacetic acid was added.
A patch was prepared by removing the part.

Comparative Example 3 In the formulation of Example 1, sodium bisulfite 0.5
And excluding 0.5 part of ethylenediaminetetraacetic acid to prepare a patch.

Reference Example 1 An ointment prepared by adding 1 part of kojic acid to the Japanese ointment.

Test Example 1 The test samples prepared in Examples and Comparative Examples were placed in a constant temperature room at 50 ° C., and changes in the degree of coloring with time were observed. Table 1 shows the results.

[0035]

[Table 1] Coloring degree change test As described above, koji is an active ingredient, and sulfurous acid is an essential ingredient.
It is clear that the melanin-suppressing patch of the present invention, which contains sodium hydrogen or sodium pyrosulfite and a chelating agent, is significantly prevented from being colored.

Test Example 2 (Ultraviolet erythema test) Experimental method Samples obtained by punching out Examples 1, 3, and 5 to a diameter of 20 mm were used, and 100 mg of the ointment of Reference Example 1 was administered. Using a male Hartley guinea pig (weight around 450 g), the hair on the dorsal side (irradiated site) was clipped with a hair clipper, and the hair was removed with a hair remover "Eva Claim S (Tokyo Tanabe Seiyaku)". Next, a sample was stuck to the back of the guinea pig from which the hair had been removed, and after 3 hours, the sample was removed.
A bandage having a small hole of 20 mm in diameter was applied to the depilated portion, and irradiated with ultraviolet rays for a certain time. Table 2 shows the test results.

[0037]

[Table 2] UV erythema test Irradiation conditions: distance from lamp about 15cm, irradiation time 60 seconds

Judgment Method The skin reaction was visually judged 1, 24 hours after irradiation. The scores for skin reactions are shown below. As is clear from the experimental results, the patch of the present invention was found to significantly suppress ultraviolet erythema as compared to the ointment of the reference example, and thus proved to be an effective patch.

As described above, the melanin-suppressing patch of the present invention has an effect of preventing erythema and spots and freckles caused by ultraviolet rays by containing kojic acid,
By using the dosage form as a patch, it can be easily applied to these sites, and its action can be applied effectively and continuously. In addition, sodium bisulfite or
By blending sodium sulfate and a chelating agent, it is possible to provide a stable preparation, which is extremely industrially applied as a novel melanin-suppressing patch.

Continuation of the front page (56) References JP-A-62-178506 (JP, A) Cosmetic Ingredients Standards Comment Editing Committee Edited “Cosmetic Ingredients Standards Commentary First Edition” by Yakuji Nipponsha (revised December 1, 1978 Edition) 3-5 Cosmetic Ingredients Standard Comment Editing Committee Edited by “Cosmetic Ingredient Standards Addendum II Note”, Yakuji Nippo-sha (issued 4th revised edition on January 5, 1979). 423-424 (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7/00 A61K 9/70 373 CA (STN)

Claims (2)

(57) [Claims] 1. Kojic acid, sodium bisulfite or
A melanin-suppressing patch containing sodium pyrosulfite , a chelating agent, an adhesive, a wetting agent and water as essential components. 2. Kojic acid 0.01 to 10% by weight, sulfurous acid
Sodium hydrogen oxyacid or sodium pyrosulfite 0.01 to
5% by weight, chelate 0.01-5% by weight, thickener 5-3
The melanin-suppressing patch according to claim 1, comprising 0% by weight, 10 to 70% by weight of a wetting agent and 10 to 70% by weight of water as essential components.