JPH07258060A - Skin whitening patch - Google Patents

Abstract

PURPOSE: To obtain a patch type skin whitening cosmetic in a new dosage form capable of percutaneously administering a regulated amount of a skin whitening substance for a long period. CONSTITUTION: This patch for skin whitening contains a skin whitening substance having tyrosinase suppressing activities as an active ingredient. The patch for skin whitening is a matrix type composed of an exposed site protecting layer 1, a main content-containing and tacky layer 2 and an adhesion site protecting layer 6 or a storage vessel type composed of the exposed site protecting layer 2, a main content layer, a release rate regulating membrane, a tacky layer and the adhesion site protecting layer. A compound having reducing properties such as ascorbic acid and its derivative, kojic acid and its derivative, glucosamines, hydroquinone and its derivative, a compound having SH group, butylene hydroxytoluene (B.H.T.) and butylene hydroxyaniline (B.H.A.) is used as the active ingredient having the skin whitening actions.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin whitening cosmetic having a novel dosage form, and more specifically, it contains at least one skin whitening substance having tyrosinase inhibitory activity as an active ingredient,
The present invention relates to a patch for skin whitening, which releases an active ingredient to the skin for a long period of time.

[0002]

2. Description of the Related Art Generally, various causes are involved in darkening the skin, and among them, when the skin is exposed to the rays of the sun, an enzyme called tyrosinase is activated by tyrosine, which is one of the amino acids. The formation of a black pigment called melanin is the most important cause.

Conventionally, active ingredients having tyrosinase inhibitory activity such as ascorbic acid and its derivatives, kojic acid and its derivatives, N-glucose amines, hydroquinone and its derivatives, etc. have been blended in cosmetics, A method of treating the skin to darken the skin or to treat spots, freckles, etc. by applying this to the skin has been adopted, but this method has various drawbacks. For example, in existing cosmetics, ascorbic acid and its derivatives are most often used for skin whitening action, but one of the main problems with these is that ascorbic acid is a water-soluble substrate. This is because when it comes into contact with air, it is easily oxidized to form dihydroascorbic acid, the titer of which is remarkably reduced, which is unstable and changes its color to brown when stored for a long period of time.

Therefore, in the past, many studies have been made and announced to improve the stability of this ascorbic acid. For example, JP-A-1-283,208 discloses a method of adding phosphate to ascorbic acid to transform it into a magnesium salt. Also,
JP-A 1-228,977, 1-228,978,
And 1-228,989, a method of esterifying ascorbic acid using a fatty acid such as stearic acid or palmitic acid is introduced. Although such a method may improve the stability of the active ingredient to some extent in the existing water-soluble base, it is fundamentally low in the stability of ascorbic acid in the water-soluble substrate and easily oxidizes and The amount of absorption inside was also low, and it was not possible to show a great effect in terms of efficacy.

Further, Japanese Unexamined Patent Publication (Kokai) No. 64-79,105 discloses a method in which ascorbic acid is added to a pack which is one kind of cosmetics and used. However, due to the above problems. However, I was not able to show much effect in terms of effectiveness.

Various methods for orally administering an active ingredient having a skin whitening effect to achieve a skin whitening effect have been investigated.
In this case, before the active ingredient absorbed in the armor reaches the desired specific skin site and exhibits a medicinal effect, the liver metabolizes and a large amount of the active ingredient is decomposed. It was difficult to transmit the active ingredient intensively, and it was not suitable for obtaining the skin whitening effect.

[0007] Therefore, there is a demand for the development of a new skin-whitening cosmetic composition having the above-mentioned problems and capable of administering a high-volume skin-whitening substance for a long period of time without irritating the skin. ing.

On the other hand, in the pharmaceutical industry, there has been proposed a medical patch for transdermal administration of a high-volume drug over a long period of time. For example, US Pat. No. 4,615,699 discloses a transdermal delivery system for transdermal delivery of a high concentration of a vasodilator, nitroglycerin. Also, US Pat. No. 4,698,062 discloses a medical device for transdermal administration of a biologically active compound in a vibrating form. Furthermore, US Pat. No. 4,7
No. 38,670 discloses an anti-inflammatory medical patch containing a coating layer, a storage layer and a peelable protective layer. However, each of these patents is designed for transdermal administration of a drug such as an anti-inflammatory agent or a vasodilator as a medical patch.

[0009]

SUMMARY OF THE INVENTION An object of the present invention is to provide a patch-type skin whitening cosmetic which is a new dosage form. Another object of the present invention is to provide a patch capable of transdermally administering a controlled amount of a skin lightening substance for a long period of time. Still another object of the present invention is to provide a patch for skin whitening, which comprises an exposed site protection layer, a main content-containing and adhesive layer and an adhesion site protection layer. Still another object of the present invention is to provide an exposed site protection layer, a main content layer,
An object of the present invention is to provide a patch for skin whitening, which comprises a release rate controlling film, an adhesive layer and an adhesion site protective layer.

[0010]

Specifically, the present invention is basically a skin whitening patch containing a skin whitening substance having tyrosinase inhibitory activity as an active ingredient. Here, the term "skin whitening substance" refers to a compound that exhibits melanin pigmentation inhibitory activity through various mechanisms and has tyrosinase inhibitory activity used in cosmetics. In particular, as these compounds, ascorbic acid or a derivative thereof, kojic acid or a derivative thereof, glucose amines,
Hydroquinone or its derivative, mercapto group (-S
H)), butylene hydroxytoluene (BHT), butylene hydroxyaniline (BHA), and the like.

Considering the effects obtained by the present invention, when an active ingredient such as ascorbic acid or a derivative thereof which is easily modified upon contact with air or moisture, it is easily effective in the existing cosmetics. On the other hand, the matrix type patch according to the present invention has a main active ingredient, a component and a plastic water-based medical adhesive, a skin absorption enhancer of the active ingredient, and an active ingredient stabilizer, while having the drawback that the ingredients oxidize and the activity decreases. , The main contents containing the active ingredient stabilizer and the skin side effect alleviator mixed in and the addition of the exposed site protection layer and the adhesion site protection layer to the adhesive layer block the moisture and air from the outside. The stability of the active ingredient can be increased.

[0012] Furthermore, the existing preparations have problems such as mixing of foreign substances and leakage of chemicals during use after being applied to a desired site during use. For example, since there is an exposed portion protective layer that acts as a shield from the outside, these problems do not occur. Moreover, even if the patch is applied for a long time, it does not irritate the skin,
It is convenient to use because the patch does not need to be washed off each time when the patch is peeled off from the patch site and removed, and the patch can be simply peeled off.

The present invention will be described in more detail below. A matrix type patch which is an example of a desirable embodiment of the patch for skin whitening according to the present invention is shown in FIG.
As shown in, the main contents containing the main active ingredient and plastic water-based medical adhesive, active ingredient skin absorption enhancer, active ingredient stabilizer, active ingredient dissolving agent and skin side effect alleviating agent In addition, it has a structure in which the exposed portion protection layer (1) and the attachment portion protection layer (6) are added to the adhesive layer (2).

As the exposed portion protective layer (1), an aluminum-coated polyethylene terephthalate film, ethylene vinyl acetate, polypropylene, polyethylene, polyurethane, polyvinyl chloride, or the like is difficult to permeate air and water, and the main contents are It is possible to use a film made of a soft material that does not allow the contents of the contained and adhesive layer (2) to pass through. The exposed site protective layer (1) functions as a protective film of the patch, has a function of managing the contents of the main contents layer (2) and maintaining the structure of the patch.

The adhesion site protective layer (6) can be peeled off immediately before use, and is manufactured by using a polyester film coated with silicon or fluorine, paper, polyethylene terephthalate film or the like.

The main content-containing and adhesive layer (2) contains 0.1 to 30% of the main active ingredient, 0.1 to 30% of skin absorption enhancer, and 0.1 to 30% by weight of the total composition. 01-2
% Weak acid as active ingredient stabilizer, 0.01-10
% Skin emollient alleviating agent and 8 to 99.68% plastic water-based medical adhesive.

In the patch for skin whitening according to the present invention,
Examples of skin lightening substances that are active ingredients that suppress melanin pigment formation in the skin by various bases include, for example, ascorbic acid, ascorbic acid monopalmitate, ascorbic acid dipalmitate, ascorbic acid stearate, and ascorbic acid monoethylhexano. Ascorbic acid diethylhexanoate, ascorbic acid monooctanoate, ascorbic acid dioctanoate, ascorbic acid monoisostearate, ascorbic acid diisostearate, ascorbic acid phosphate magnesium salt, ascorbic acid sodium salt and the like, and Kodic acid, codic acids such as codic acid derivatives having an alkyl group having 5 to 20 carbon atoms, glucose amines such as glucose amine, galactose amine and mannose amine, and high Hydroquinone derivatives such as roquinone, hydroquinone glucosides and hydroquinone benzyl ether, compounds having a -SH group such as glutathione and cystine, butylene hydroxytoluene (BHT) and butylene hydroxyaniline (BH.H. A.), propyl gallic acid ester,
Methionine, lecithin and the like can be mentioned, and any one of them can be used alone, or two or more kinds can be mixed and used. The content of these skin lightening substances is 0.1 to 30% by weight, preferably 1.0 to 30% by weight.

The skin absorption enhancer used to enhance the skin absorption of the active ingredient includes, for example, dimethyl sulfoxide, dodecyl sulfoxide, mono- or dimethylacetamide, N-hydroxyethyl lactide, higher fatty acid ester. , Salicylic acid, sorbitol, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, pyrrolidone derivative, butylene glycol ethyl ether, dodecylpyrrolidone, urea, glycerin, squalene, squalane, acetylated lanolin, cetyl laurate, olive oil, castor oil,
Lauric acid, oleic acid, lauryl alcohol, oleyl alcohol, ethoxystearyl alcohol, liquid paraffin, petrolatum, 1-menthol, camphor, glycerin fatty acid ester, fatty acid mono (or di) ethanolamide, ethylene glycol monoethyl ester, polyoxyethylene alkyl Ethers, polyoxyethylene alkyl esters, polyoxypropylene alkyl ethers, propylene glycol mono (di) alkyl esters and the like can be used alone or as a mixture, and in the present invention, one of fatty acid esters having a skin softening promoting action is particularly preferable.
Glycerin monooleate or fatty acid esters such as glycerin dioleate or propylene glycol monooleate, ethylene oxide 2
The skin absorption of the skin lightening substance can be promoted by advantageously using fatty acid ethers to which ˜20 mol is added, or sorbitan fatty acid esters and sorbitan fatty acid esters to which 10 to 100 mol of ethylene oxide is added.

Further, in order to stabilize the active ingredient in the system, various weak acids such as citric acid, succinic acid and oxalic acid or formic acid are added in a small amount as a stabilizer for the active ingredient in the system. The atmosphere inside can be acidified to improve the stability of the active ingredient.

Examples of the active ingredient dissolving agent capable of increasing the solubility of the active ingredient in the system and transmitting the active ingredient include, for example, 1,3-butylene glycol,
Polyols such as propylene glycol, glycerin, polyethylene glycol, polyethylene glycol-propylene glycol copolymer and alcohols such as ethanol, methanol, isopropanol and butanol are used.

According to the present invention, the patch is made tacky,
In order to prevent instability of each active ingredient in a water-soluble substrate, an acrylic polymer adhesive, a silicone adhesive, a polyisobutylene adhesive, or a plastic water-based adhesive such as a synthetic or natural rubber adhesive. Is used.

As the acrylic pressure-sensitive adhesive, there are especially 4 carbon atoms.
Polymers of (meth) acrylic acid alkyl esters obtained from ~ 18 aliphatic alcohols and (meth) acrylic acid and copolymers of (meth) acrylic acid esters with other functional monomers are used.

Examples of the (meth) acrylic acid copolymer include butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate,
Decyl acrylate, isodecyl acrylate, lauryl acrylate, stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl acrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate, isodecyl methacrylate, lauryl meta There are acrylate, stearyl methacrylate and the like.

As the functional monomer, a monomer having a hydroxyl group, a monomer having a carboxyl group, a monomer having an amide group, a monomer having an amino group and the like are used. Further, as the monomer having a hydroxyl group,
There are hydroxyalkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxypropyl acrylate, and examples of the monomer having a carboxyl group include α such as acrylic acid and methacrylic acid.
-Or β-unsaturated carboxylic acids, maleic acid monoalkyl esters such as butyl maleate, maleic acid, fumaric acid, crotonic acid and the like can be mentioned. Examples of the monomer having an amide group include alkyl (meth) acrylamides such as acrylamide, dimethylacrylamide, and diethylacrylamide, alkylethylmethylol (meth) acrylamides such as butoxymethylacrylamide, and ethoxymethylacrylamide, diacetone acrylamide, and vinylpyrrolidone. Etc., and also
Examples of the monomer having an amino group include dimethylamino acrylate and the like. Further, as copolymer monomers other than the above, for example, vinyl acetate, styrene, α-methylstyrene, vinyl chloride, acrylonitrile, ethylene,
There are propylene, butadiene and the like, and copolymers with them also show favorable characteristics. It is preferable that the pressure-sensitive adhesive contains 50% by weight or more of (meth) acrylic acid alkyl ester as a (co) polymerization component.

As the rubber-based adhesive, natural rubber, polyisoprene, polyisobutylene, polyvinyl ether, polyurethane, polybutadiene, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-isoprene-butylene block copolymer, etc. The silicone resin-based pressure-sensitive adhesive is preferably a polydimethylsiloxane resin 40% by weight and a silicate rubber 60% by weight crosslinked.

In the above-mentioned pressure-sensitive adhesive, if necessary, various compounding agents such as tackifiers such as rosin-based resin, polyterpene-based resin, coumaroindene-based resin, petroleum-based resin, Tefrene-phenol-based resin, and liquid Plasticizers such as polybutene, mineral oil, lanolin, liquid polyisoprene, and liquid polyacrylate, and fillers, antioxidants, and the like can be added as other materials. These plastic medical adhesives are usually added in a proportion of 8 to 99.68% by weight.

The matrix type patch according to the present invention is manufactured as follows. That is, 0.1 to 30% by weight of a skin whitening substance which is an active ingredient having a whitening effect on the skin, alone or in a mixture, and 0.1 to 30% by weight of a skin absorption enhancer of this active ingredient, or an active ingredient. 0.01 to 2% by weight of a weak acid alone or a mixture as a stabilizer,
Skin side effect alleviating agent alone or as a mixture 0.01 to 10% by weight
And an active ingredient dissolving agent in the system alone or 0.1 to 20% by weight of a mixture are uniformly dispersed in an organic solvent such as hexane, ethyl acetate, chloroform and the like, and then the above-mentioned plastic adhesive which can be used for medical purposes. After blending 8 to 99.68% by weight of the agent, the mixture is stirred for 1 hour or more to disperse the mixture in a uniform state, after which the stirring is stopped and the mixture is left at room temperature for an appropriate period of time to remove air bubbles. A composition for a material-containing and adhesive layer is prepared.

The mixture thus obtained was applied on a paper or polyethylene terephthalate film (6) coated with silicon or fluorine with an applicator to a uniform thickness of 10 to 200 μm, and then at room temperature. Let stand for 1 hour or more to evaporate the solvent and remove. At this time, if necessary, after drying at room temperature, it is further dried by a hot air dryer at 80 ° C. for 10 minutes.

After confirming that the solvent is fully dried,
It is interleaved with an exposed site protective layer (1) selected from a film made of a soft material such as an aluminum-coated polyethylene terephthalate film, ethylene vinyl acetate or polypropylene, which hardly permeates air and moisture. After aging this for 12 to 24 hours in a 37 ° C constant temperature bath, it is finally formulated into a desired shape so that the skin contact area becomes 0.1 to 500 cm ² so that it easily attaches to the application site. To do.

As shown in FIG. 2, a storage tank type patch, which is another desirable example of the patch according to the present invention, comprises an exposed site protective layer (1), a main active ingredient, a skin absorption enhancer and an active ingredient. A main content-containing layer (3) made by mixing a stabilizer, a skin side effect alleviating agent, etc. with an in-system active ingredient dissolving agent, a microporous membrane (4) for controlling the active ingredient release rate, and a skin adhesive layer ( 5) and the adhesion part protection layer (6) are laminated to have a structure integrally formed. The exposed site protective layer (1), the adherent site protective layer (6) and the skin adhesive layer (5) can be configured in the same manner as described in the above-mentioned matrix type patch.

The composition used for the main content layer (3) is 0.1 to 30% by weight of a skin whitening substance, which is an active ingredient having a whitening effect on the skin, alone or in a mixture, and promotes skin absorption of the active ingredient. 0.1 to 30% by weight of absorption enhancers used alone or as a mixture, and 0.01 to 2% by weight of weak acids as active ingredient stabilizers, either individually or as a mixture,
0.01 to 10% by weight of a skin side effect alleviating agent alone or a mixture and 28 to 9 of an active ingredient dissolving agent alone or a mixture in the system
And 9.78% by weight.

The release rate controlling film (4) is a microporous film for controlling the rate of release of the skin lightening substance and the absorption enhancer from the main content layer (3), for example polyethylene. It is made of polypropylene, ethylene vinyl acetate, etc. The storage tank type patch shown in FIG. 2 is preferably used particularly when it is required to regulate and absorb a considerably large amount of active ingredient through the skin.

The method for producing the storage tank patch according to the present invention is as follows. After dissolving the water-based medical adhesive (5) in an appropriate organic solvent, the paper or polyethylene terephthalate film (6) coated with silicon or fluorine is applied with an applicator to a thickness of 10 to 200 μm.
After coating to a uniform thickness, the solution is left standing for 1 hour or more at room temperature to evaporate the solvent and remove it. At this time, if necessary, after drying at room temperature, it is further dried for 10 minutes by a hot air dryer at 80 ° C. After confirming that the solvent has been fully dried, a fine porous film (4) is interleaved on this.

On the other hand, a skin-whitening substance, which is an active ingredient having a whitening effect on the skin, alone or in a mixture of 0.1 to 30.
% By weight, 0.1 to 30% by weight of an absorption enhancer alone or a mixture for enhancing skin absorption of an active ingredient, and 0.01 to 2% by weight of a weak acid as an active ingredient stabilizer.
And a skin side effect relieving agent alone or in a mixture of 0.01 to 10
28% by weight of the active ingredient dissolving agent in the system, alone or as a mixture
99.78 wt% is mixed and stirred so that the contents are uniformly dispersed.

Next, the composition thus obtained was used to protect the laminated film composed of the fine porous film (4), the adhesive layer (5) and the adhesion site protective layer (6) obtained above and the exposed site protection. Insert between layers (1) and heat seal the edges of each layer. Finally, it is formed into a desired shape so that the area attached to the skin is 0.1 to 500 cm ² . In the patch for skin whitening of the present invention thus obtained, the percutaneous absorption rate of the main active ingredient per unit time and unit area is preferably 0.01 to 50 μg.

[0036]

EXAMPLES The contents of the present invention will be specifically described below based on Examples and Test Examples, but it is made clear that the contents of the present invention are not limited by these. In the examples, the content of each component is “% by weight” unless otherwise specified.

Examples 1 to 5 The substances shown in Table 1 were blended in the proportions shown in Table 1 and stirred until they were homogeneous to obtain a composition.

[Table 1]

The composition thus obtained was applied onto a silicone-coated paper using an applicator to give about 50 μm.
m, the paper was left at room temperature for 1 hour to evaporate the solvent, and the paper covered with the composition was fused with an aluminum-coated polyethylene terephthalate film to form a laminated film. It was The obtained laminated film is aged in an incubator (37 ° C.) for 12 to 24 hours to give a thickness of about 20 cm ^2.
It was formulated into a matrix type patch having a size of.

Examples 6 to 9 The respective substances shown in Table 2 were blended in the proportions shown in Table 2, and were stirred and mixed until uniform to obtain compositions.

[Table 2] Using the compositions thus obtained, Examples 1-5
A matrix type patch of about 30 cm ² was obtained in the same manner as described in 1.

Examples 10 to 13 The substances shown in Table 3 were blended in the proportions shown in Table 3, and were stirred and mixed until uniform to obtain compositions.

[Table 3] Using the composition thus obtained, the same procedure as in Examples 1 to 5 except that a fluorine-coated polyester film and a polyethylene film were used instead of the silicon-coated paper and the aluminum-coated polyethylene terephthalate film, respectively. About 30 cm ²
To obtain a matrix type patch.

Examples 14 to 17 The substances shown in Table 4 were blended in the proportions shown in Table 4 and stirred until they were homogeneous to obtain compositions.

[Table 4] Using the composition thus obtained,
A matrix type patch of about 30 cm ² was obtained in the same manner as in 13.

Examples 18 to 21 The substances shown in Table 5 were blended in the proportions shown in Table 5, and were stirred and mixed until they were homogeneous to obtain compositions.

[Table 5] Using the compositions thus obtained, Examples 1-5
A matrix type patch of about 20 cm ² was obtained in the same manner as described in 1.

Examples 22 to 25 The substances shown in Table 6 were blended in the proportions shown in Table 6 and stirred until they were homogeneous to obtain compositions.

[Table 6]

On the other hand, butyl acrylate and decyl methacrylate were dissolved in hexane and coated on a silicon-coated paper with an applicator to a thickness of about 50 μm. Leave the paper at room temperature for 1 hour, then at 80 ° C.
It was further dried for 10 minutes using a hot air dryer. The interleaved adhesive layer-adhesion site protection layer was laminated on one side of a 25 [mu] m thick microporous polypropylene membrane. The composition obtained above was treated with form-fill-sea.
l) A pouching machine is used to insert between the aluminum-coated polyethylene terephthalate layer and the microporous membrane-adhesive layer-adhesion site protection layer laminate and heat seal the edges of these layers. did. A storage tank type patch having a size of about 20 cm ^{2 was} produced from the obtained 5-layer laminate.

The percutaneous absorption type skin whitening preparations produced by the above method according to the formulations of Examples 1 to 25 above, using animal skin, have a percutaneous permeation rate, efficacy, stability and skin safety. Was tested. The results are as follows.

Test Example 1 A male guinea pig weighing about 350 g was cut from the abdominal hair with an electric clipper, cut at a certain site, stored frozen (-20 ° C. or below), and then thawed at the time of the test. I was there. A skin test piece was placed in the middle of a Franz type glass diffusing device with the stratum corneum facing upwards, and then 50% by volume of glycerin aqueous solution was put in the space of the bottom part to keep the temperature of the diffusing device at 37 ° C. While the receptor solution was stirred at a constant speed (600 rpm), the patch prepared according to the formulation of each example was attached to the skin. At this time, the formulation was prepared in a circular shape so as to have a size of 2.5 cm ² .

After a certain period of time, the solution of the receptor part was collected, and the collected amount of the buffer solution was added. For the collected samples, high pressure liquid chromatography (HPL
Using C), the concentration of each active ingredient was measured. The percutaneous permeation rate of each active ingredient calculated from the concentration analysis is as shown in Table 7 (results of percutaneous permeation rate measurement test of percutaneous absorption-type pharmaceutical preparation and cosmetic containing active ingredient for skin whitening).

[0048]

[Table 7] As is clear from the results in Table 7, the patch prepared by the formulation of each example containing ascorbic acid and its derivative showed a higher skin permeation rate than general cosmetics.

With respect to the ascorbic acid-containing matrix-type skin lightening patch of Examples 1 and 2, the guinea pig skin permeation state was examined with time. The results are shown in Fig. 3.

Test Example 2 Twenty healthy male and female experimenters were selected and 2 × 2 on both arm lower arms.
Select a site of cm ² and cover the arm with aluminum foil so that only the site to be tested is irradiated with ultraviolet rays, 1
Irradiate two L20S BLB lamps and two L20S E-30 lamps manufactured by Toshiba Corp. simultaneously from 0 cm at a rate of 0.8 × 10 ⁷ erg / cm ³ / time, once a day for 3 times. did. Prior to irradiation, the test site was thoroughly washed with a 70% aqueous solution of isopropylene. After irradiation, apply 2% daily cosmetics containing 3% of each active ingredient for skin whitening to the UV irradiation area.
One month after application of the percutaneous absorption type pharmaceutical preparations produced according to the formulations of the above-mentioned examples once a day and one month later, it was investigated how much each test group suppressed pigmentation, and a remarkable effect was obtained. The evaluation was made in three grades: valid, invalid. The results are shown in Table 8 (effectiveness test results of each transdermal absorption type cosmetic preparation containing an active ingredient for skin whitening).

[0051]

[Table 8] As is clear from Table 8, the transdermal preparations containing ascorbic acid and its derivatives, which were manufactured according to the formulations of Examples, showed more positive effects than the conventional cosmetics and were excellent. It exhibited the effect of suppressing pigmentation.

Test Example 3 A cosmetic containing 3% of each active ingredient for skin whitening and a percutaneous absorption type preparation manufactured according to the formulation of each Example were allowed to stand in a constant temperature bath at 50 ° C. for 2 months, and then methanol was used. After extraction of the active ingredients, high pressure liquid chromatography (HPLC)
Was used to measure the titer of each product. The results are shown in Table 9 (results of potency measurement test of each transdermal absorption preparation containing the active ingredient for skin whitening and cosmetics).

[0053]

[Table 9] As is clear from Table 9, the transdermal preparations containing ascorbic acid and its derivatives prepared according to the formulations of Examples show higher potency and higher stability than conventional cosmetics. showed that.

Test Example 4 The transdermal preparations prepared according to the formulations of the above-mentioned respective examples, which were cut into a size of 2 cm ^2, were attached to the armpits of 20 healthy male and female experimenters once a day, Active ingredient 3 for each skin whitening
% Application cosmetics twice a day, after covering the metal cup to shield from the outside, 1 day, 3 days, and 7 days later, the degree of irritation was observed according to the following criteria. ,evaluated. The results are shown in Table 10 (results of skin stability test of transdermal patches and cosmetics containing active ingredients for skin whitening).
Shown in. Judgment number 0: No irritation, Judgment number 1: Minimal irritation, Judgment number 2: Slight irritation (erythema), Judgment number 3: Extreme irritation (erythema, edema), Judgment number 4: Extremely irritation ( Erythema, edema).

[0055]

[Table 10] As is clear from the results in Table 10, the skin side effects of the transdermal preparations manufactured according to the formulation of each example to which α-bisabolol was added are reduced to almost the same level as conventional cosmetics. I was able to.

[0056]

EFFECTS OF THE INVENTION According to the present invention, a new dosage form containing at least one skin lightening substance having tyrosinase inhibitory activity as an active ingredient and capable of supplying this skin lightening substance to the skin for a long period of time. A certain patch-type patch for skin whitening can be provided.

[Brief description of drawings]

FIG. 1 is a sectional explanatory view showing an example of a matrix-type skin whitening patch according to the present invention.

FIG. 2 is a cross-sectional explanatory view showing an example of a storage tank-type patch for skin whitening according to the present invention.

[Fig. 3] Fig. 3 is a graph showing a skin permeation state from a guinea pick of an ascorbic acid-containing matrix-type skin whitening patch (Example 1:-○-and Example 2:-●-) according to the present invention. is there.

[Explanation of symbols]

1 ... Exposed site protection layer, 2 ... Main content-containing and adhesive layer, 3 ... Main content-containing layer, 4 ... Microporous membrane (active ingredient release control film), 5 ... Skin adhesive layer, 6 ... Adhesion site protection layer.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Lee Bun-gu, New Seoul APT. No. 205, No. 502 (72) Inventor Kim Jong-sang, 935, Gangnam APT. Building A, No. 304 (72) Inventor An Jian Gen Dongdae-dong, New Dadong-dong 601-22, Seoul, Republic of Korea

Claims (12)

[Claims] 1. A skin-whitening patch comprising a skin-whitening substance having a tyrosinase inhibitory activity as an active ingredient. 2. The patch for skin whitening according to claim 1, wherein the patch comprises an exposed site protection layer, a main content-containing and adhesive layer, and an adhesion site protection layer. 3. The patch for skin whitening according to claim 1, wherein the patch comprises an exposed site protective layer, a main content layer, a release rate controlling film, an adhesive layer and an adherent site protective layer. 4. The main content-containing and adhesive layer comprises ascorbic acid or ascorbic acid monopalmitate, ascorbic acid dipalmitate, ascorbic acid stearate, ascorbic acid monoethylhexanoate, and ascorbic acid based on the total weight of the composition. Diethyl hexanoate, ascorbic acid monooctanoate, ascorbic acid dioctanoate, ascorbic acid monoisostearate, ascorbic acid diisostearate, ascorbic acid phosphate magnesium salt, ascorbic acid sodium salt, kodic acid and 5 to 20 carbon atoms Codic acid derivative having an alkyl group added thereto; glucoseamines such as glucoseamine, galactoseamine, or mannoseamine; hydroquinone and hydroquinone glucosides, hydroquinoneben Hydroquinone derivatives such as diether; compounds having -SH group such as glutathione and cystine; butylene hydroxytoluene (B.H.
T); butylene hydroxyaniline (BH.
A. ); Galic acid propyl ester; Methionine; 0.1 to 30% of one or more skin lightening substances selected from the group consisting of lecithin, dimethyl sulfoxide, dodecyl sulfoxide, mono- or dimethylacetamide, N
Hydroxyethyl lactide, polyoxyethylene (EO = 2-20) fatty acid ethers, for example higher fatty acid esters such as glycerin monooleate, glycerin dioleate or propylene glycol monooleate, sorbitol salicylate, polyoxyethylene ( EO = 10 to 100) sorbitan fatty acid ester, sorbitan fatty acid ester, pyrrolidone derivative, butylene glycol ethyl ether, dodecylpyrrolidone, urea, glycerin, squalene, squalane, acetylated lanolin, cetyl laurate, olive oil, castor oil, lauryl. Acid, oleic acid, lauryl alcohol,
Oleyl alcohol, ethoxystearyl alcohol,
Liquid paraffin, petrolatum, 1-menthol, camphor, glycerin fatty acid ester, fatty acid mono (or di)
Ethanolamide, ethylene glycol monoethyl ether, polyoxyethylene alkyl ether, polyoxyethylene alkyl ester, polyoxypropylene alkyl ether, propylene glycol mono (or di)
0.1 to 30% by weight of one or more absorption enhancers selected from the group consisting of alkyl esters, succinic acid, citric acid,
0.01 to 2% by weight of one or more active ingredient stabilizers selected from the group consisting of oxalic acid and formic acid, and 1,3-butylene glycol, propylene glycol, glycerin, polyethylene glycol or polyethylene glycol-propylene glycol 0.1 to 20% by weight of polymer or one or more active ingredient dissolving agents selected from the group consisting of ethanol, isopropanol, methanol and butanol
0.01 to 10% by weight of a skin irritant selected from glycerin or α-bisabolol, an acrylic polymer adhesive, a silicone adhesive or a polyisobutylene adhesive, and a synthetic or natural rubber adhesive The patch for skin whitening according to claim 2, which contains one or more kinds of plastic water-based medical adhesives selected from the group consisting of: 5. The main content layer comprises ascorbic acid or ascorbic acid monopalmitate, ascorbic acid dipalmitate, ascorbic acid stearate, ascorbic acid monoethylhexanoate, and ascorbic acid diethylhexano, based on the total weight of the composition. Ate, ascorbic acid monooctanoate, ascorbic acid dioctanoate, ascorbic acid monoisostearate, ascorbic acid diisostearate, ascorbic acid phosphate magnesium salt, ascorbic acid sodium salt, kojic acid and an alkyl group having 5 to 20 carbon atoms Glucose amines such as glucose amine, galactose amine, or mannose amine; hydroquinone and hydroquinone glucosides; hydroquinone benzyl ether Derivatives such as glutathione, cystine, etc., -SH group-containing compounds; Butylene hydroxytoluene (BHT); Butylene hydroxyaniline (BHA); Galic acid propyl ester; Methionine; Lecithin etc. 0.1 to 30% of one or more skin lightening substances selected from the group consisting of
Dimethyl sulfoxide, dodecyl sulfoxide, mono- or dimethylacetamide, N-hydroxyethyl lactide, polyoxyethylene (EO = 2 to 20)
Fatty acid esters, for example higher fatty acid esters such as glycerin monooleate, glycerin dioleate or propylene glycol monooleate, salicylic acid, sorbitol, polyoxyethylene (EO = 10-1).
00) sorbitan fatty acid ester, sorbitan fatty acid ester, pyrrolidone derivative, butylene glycol ethyl ether, dodecylpyrrolidone, urea, glycerin, squalene, squalane, acetylated lanolin, cetyl laurate, olive oil, castor oil, lauric acid, oleic acid, lauryl alcohol. , Oleyl alcohol, ethoxystearyl alcohol, liquid paraffin, petrolatum, 1-menthol, camphor, glycerin fatty acid ester, fatty acid mono (or di) ethanolamide, ethylene glycol monoethyl ether, polyoxyethylene alkyl ether, polyoxyethylene alkyl ester, One selected from the group consisting of polyoxypropylene alkyl ether and propylene glycol mono (or di) alkyl ester Absorption enhancers and 1.0 to 30 wt% of the above, succinic acid, citric acid, oxalic acid, one or more active ingredients stabilizer selected from the group consisting of formic acid from 0.01 to 2
% By weight, 1,3-butylene glycol, propylene glycol, glycerin, polyethylene glycol or polyethylene glycol-propylene glycol copolymer, or ethanol, isopropanol, methanol,
28 to 99.78% by weight of one or more active ingredient dissolving agents selected from the group consisting of butanol, glycerin, or α
-Skin irritation alleviating agent selected from bisabolol 0.01-
10% by weight, and the adhesive layer is selected from the group consisting of an acrylic polymer adhesive, a silicone adhesive or a polyisobutylene adhesive, and a synthetic or natural rubber adhesive.
It is formed from one or more types of plastic water-based medical adhesives.
The patch for skin whitening described. 6. The acrylic polymer adhesive has 4 to 4 carbon atoms.
Polymer of (meth) acrylic acid C _4-18 alkyl ester obtained from aliphatic alcohol of 18 and (meth) acrylic acid, or this (meth) acrylic acid C _4-18 alkyl ester and other functional monomer The patch for skin whitening according to claim 4 or 5, which is a copolymer of 7. The (meth) acrylic acid C _4-18 alkyl ester polymer is butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate, decyl acrylate, isodecyl acrylate, lauryl acrylate. , Stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl acrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate, isodecyl methacrylate, lauryl methacrylate and stearyl methacrylate. Chosen 1
Or more, and the other functional monomer is a monomer having a hydroxy group such as 2-hydroxyethyl (meth) acrylate or hydroxypropyl (meth) acrylate, α- or β-unsaturated such as acrylic acid or methacrylic acid Carboxylic acid, maleic acid monoalkyl ester such as butyl maleate, monomer having a carboxyl group including maleic acid, fumaric acid, crotonic acid, etc., acrylamide, dimethyl acrylamide, alkyl (meth) acrylamide such as diethyl acrylamide, butoxymethyl acrylamide, Alkylethylmethylol (meth) acrylamide such as ethoxymethylacrylamide,
Alkyd group-containing monomers including diacetone acrylamide, vinylpyrrolidone, amino group-containing monomers including dimethylaminoacrylate, styrene, α
The patch for skin whitening according to claim 6, which is one or more selected from methylstyrene, vinyl chloride, acrylonitrile, ethylene, propylene, butadiene and the like. 8. The rubber-based pressure-sensitive adhesive is natural rubber, polyisoprene, polyisobutylene, polyvinyl ether, polyurethane, polybutadiene, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-isoprene-butylene block copolymer. The skin lightening patch according to claim 4 or 5, wherein the adhesive agent is one or more selected from the group consisting of 40% by weight of polydimethylsiloxane resin and 60% by weight of silicate rubber crosslinked. 9. The patch for skin whitening according to claim 3, wherein the release rate-controlling film is a microporous film made of polypropylene, polyethylene, ethylene vinyl acetate copolymer, or polyvinylpyrrolidone. 10. The exposed portion protective layer is a polyethylene terephthalate film coated with aluminum, or a film made of a material having poor air and moisture permeability, such as ethylene vinyl acetate, polypropylene, polyethylene, polyurethane or polyvinyl chloride. The patch for skin whitening according to 2 or 3. 11. The skin whitening patch according to claim 2, wherein the adhesion site protective layer is a polyester film or paper coated with silicon or fluorine, or polyethylene terephthalate fill). 12. The patch for skin whitening according to claim 1, wherein the percutaneous absorption rate of the main active ingredient per unit time and unit area is 0.01 to 50 μg.