KR960006859B1 - Improved method for stability of ageing comprising thirosinase inhibitor activity - Google Patents

Abstract

This pharmaceutical is composed of 0.1-30wt% the pharmceutical components 8-99.68wt% hydrophobic tackifier 0.1-30wt%, skin absorption enhancer stabilizer solubilizer 0.1-20wt%, 0.01-2wt%, and 0.1-10wt% side effect reducer. The above pharmaceutical component with thirosinase inhibitor activity is one or more compounds selected from ascorbic acid and its deriv., kojic acid and its deriv., glycosamines, hydroquinone and its deriv., compounds with -SH group and butylhydroxytoluene and butylhydroxyanisone; and hydrophobic tackifier. This pharmaceutical is prepared to matrix or reservoir type structure and percutaneous absorption type. The above tackifier is acrylic polymer.

Description

How to improve the stability of drugs with tyrosinase inhibitory activity

1 shows an example of a transdermal absorption preparation for skin whitening of a matrix type according to the present invention,

2 shows an example of a percutaneous absorption preparation for storage skin type skin whitening according to the present invention,

3 is a graph showing the guinea pig skin permeation aspect of the transdermal absorption preparation for ascorbic acid-containing matrix skin whitening according to the present invention.

* Explanation of symbols on the main parts of the drawings

1: exposed part protective layer 2: contents contained and adhesive layer

3: content-containing layer, 4: microporous membrane (drug release control membrane)

5: skin adhesion layer 6: adhesion site protective layer.

(1) Ascorbic acid-containing skin whitening transdermal preparation according to Example 1

(2) Ascorbic acid-containing skin transdermal absorption preparations according to Example 2

The present invention relates to a method for improving the stability of a drug by formulating a drug having a skin lightening effect in a transdermal absorption type.

In general, a number of causes are involved in blackening the skin, the most important of which is that when the skin receives sunlight, an enzyme called tyrosinase is activated on the amino acid tyrosine, which forms a black pigment called melanin. .

Therefore, conventionally, drugs having tyrosinase inhibitory activity such as ascorbic acid and its derivatives, kojic acid and its derivatives, N-glycosamines, hydroquinones and derivatives thereof, are formulated into cosmetics and applied to the skin to darken the skin. The method used to treat blemishes and freckles is used, but this method has various limitations.

For example, ascorbic acid and its derivatives are most frequently used in existing cosmetics for skin whitening, and the main problems thereof are as follows.

Ascorbic acid, when contacted with air in a water-soluble substrate, is easily oxidized to dihydroascorbic acid, which exhibits instability of markedly lowered titer, and has a disadvantage of discoloration to dark brown upon long-term storage.

In addition, even ascorbic acid derivatives such as ascorbyl stearate with improved stability, ascorbic acid palmitate, and magnesium salt of phosphate ascorbyl have low solubility in cosmetics, and the stability is not as high as expected. Since only a small amount can be added, the absorption of the drug into the skin is greatly reduced.

Therefore, there is little drug absorption into the skin, so the moderate skin lightening effect expected is not exhibited.

Many studies have been published to improve the stability of ascorbyl acid.

For example, Japanese Patent Laid-Open No. 1-283208 introduced a method of adding phosphate to ascorbic acid and modifying a drug with magnesium salt. Japanese Patent Laid-Open Nos. 1-228977, 1-228978, and 1-228989 were introduced. A method for ester-bonding an alkyl group such as stearyl or palmityl to ascorbic acid is introduced.

These methods may have improved the stability of the drug to some extent in existing water-based bases, but are fundamentally less stable in water-soluble substrates, easier to oxidize, and less absorbed into the skin. It was.

In addition, Japanese Patent Application Laid-Open No. 64-79105 introduced a method of adding ascorbyl acid to a pack of cosmetics, but the same problem did not show any effect in terms of effectiveness.

Various methods have been sought to achieve skin whitening effect by oral administration of a drug having a skin whitening effect, but in this case, the drug absorbed in the intestine is metabolized in the liver before it is circulated to a specific skin area desired. Because of the large amount is decomposed to receive the concentrated drug delivery to the desired specific site is difficult, it is not suitable to obtain the skin whitening effect.

In order to solve these problems, the present inventors have used transdermal absorption method in which a specific drug is concentrated to a specific skin area by using a transdermal absorption drug delivery system, so that the absorbed drug is circulated in the intestine. It does not pass through the metabolism in the liver does not significantly reduce the drug effect, it is possible to intensive drug administration to a specific site, it is found that it is easy to control the rate of skin absorption of the drug according to various formulation design and the present invention It was completed.

That is, inhibition of tyrosinase such as ascorbyl and derivatives thereof, kojic acid and derivatives thereof, glycosamines, hydroquinone and derivatives thereof, compounds having a -SH group and butylhydroxytoluene (BHT) and butylhydroxyanison (BHA) A method for improving the stability of a drug having tyrosinase inhibitory activity, characterized in that the percutaneous absorption formulation is formed into a matrix structure or a storage tank structure including a main content layer mixed with one or more mixtures of the drug and a hydrophobic adhesive. It is about.

Looking at the effects that can be obtained according to the present invention, while drugs such as ascorbic acid or derivatives thereof that are easily denatured upon contact with air or moisture have the disadvantage that the drugs are easily oxidized in the existing cosmetics and the ringiness falls, The matrix-type transdermal absorbent according to the present invention is exposed to the protective layer and the attachment site in the main content layer containing the main drug component and the hydrophobic medical pressure-sensitive adhesive, the skin absorption enhancer of the drug, the drug stabilizer, the in-situ drug stabilizer and the skin side effects relieving agent. The addition of a protective layer can block the external moisture and air to increase the stability of the drug, the transdermal absorption preparation of the storage tank according to the present invention prescribes the drug in a state that does not contain water, and also protects against external protection Adding a layer can increase the stability of the drug.

In addition, the existing formulations have a problem that the foreign substances are mixed or applied to the outside during use after application to the desired site during use, while the percutaneous absorption type preparations according to the present invention has a protective layer for exposing the site to act as a barrier to the outside. There is no such problem.

Even when removing the preparation from the application site, it is convenient to use in many ways because the preparation can be simply removed without having to be washed off.

Percutaneous absorption of drugs by the transdermal absorption system is carried out due to the difference in concentrations in the base and in vivo. In the case of actually penetrating the stratum corneum, the overall process of constituting the absorbent whole is as follows. Diffusion in the base, second distribution from the base to the surface of the stratum corneum, diffusion in the third stratum corneum, distribution from the fourth stratum corneum to the lower epidermal tissue, the fifth living epidermis, diffusion in the dermis layer, and transition from the sixth dermis layer to blood vessels. It is divided.

As described above, the transdermal absorption process of the drug is considered to be a diffusion process and a distribution process, but in reality, the binding and metabolism of the tissue proceeds simultaneously with the diffusion.

Features of the present invention are as follows.

The matrix formulation, which is an example of a preferred embodiment of the transdermal absorption preparation for skin whitening according to the present invention, is a main mixture of a main drug component and a hydrophobic medical pressure-sensitive adhesive, a skin absorption enhancer of a drug, a drug stabilizer, an in-situ drug dissolving agent and a skin alleviation agent. It has a structure in which an exposed part protective layer and an attachment part protective layer are added to the contents layer.

A reservoir formulation, which is an example of another preferred embodiment, includes a drug release control film and a skin in a main content layer mixed with a main drug component and a hydrophobic medical pressure-sensitive adhesive, a skin absorption enhancer, a drug stabilizer, an in-situ drug dissolving agent, and an alleviation of skin side effects. It has a structure in which an adhesive layer, an exposed part protective layer, and an attachment part protective layer are added.

Ascorbyl and ascorbyl monopalmitate, ascorbyl dipalmitate, ascorbyl acid stearate, ascorbyl, known as a drug that inhibits melanin pigmentation in the skin by various mechanisms in the transdermal absorption preparation for skin whitening according to the present invention. Ascorbyl derivatives, such as phosphate magnesium salt and sodium ascorbyl salt, derivatives of which koji acid and a C5-20 alkyl group are added, glycosamines such as glucoseamine, galactosamine and manosamine, and hydroquinone And derivatives such as hydroquinone glycosides and hydroquinone benzyl ether or drugs having reducibility having -SH groups such as glutathione and cysteine, alone or in combination, are used as main drug components.

Skin absorption enhancers of drugs used to enhance the skin absorption of drugs include dimethyl sulfoxide, dodecyl sulfoxide, mono or dimethylacetamide, N-hydroxy ethyl lactide, higher fatty acid esters, salicylic acid, sorbitol, polyoxy Ethylene sorbitan fatty acid esters, sorbitan fatty acid esters, pyrrolidone derivatives, butylene glycol ethyl ether, dodecylpyrrolidone, urea, glycerin, squalene, squalane, acetylated lanolin, cetyllaurate, elive oil, castor oil, Lauryl acid, oleic acid, lauryl alcohol, oleyl alcohol, ethoxystearyl alcohol, liquid paraffin, waserine, l-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 ( Alkyl esters, etc. may be used alone or in combination. In the present invention, fatty acid esters such as glycerin monooleate, glycerine dioleate or propylene glycol monooleate, etc. Surfactants such as sters, sorbitan fatty acid esters, and the like are mixed with surfactants, fatty acid ethers containing 2 to 20 moles of ethylene oxide, or sorbitan fatty acids to which 10 to 100 moles of ethylene oxide is added. It improves skin absorption and improves its effectiveness. It also reduces skin irritation by using skin side effects relievers such as glycerin and bisaboll.

In addition, in order to stabilize the drug in the system, various weak acids such as citric acid, succinic acid, oxalic acid or formic acid may be added in small amounts as the system stabilizer to acidify the atmosphere in the system to improve the stability of the drug.

In-situ drug solubilizers that enhance drug solubility and act as drug delivery systems include l, 3-butylene glycol, propylene glycol, glycerin, 5-50 moles of polyethylene glycol or polyethylene glycol-propylene glycol copolymers. Polyols and alcohols, such as butanol, can be used for ethanol, methanol, isopropane.

In addition, in order to prevent instability in the water-soluble substrate of each drug, by using an acrylic polymer adhesive, a silicone adhesive, a polyisobutylene adhesive, or a hydrophobic adhesive such as a synthetic or natural rubber adhesive, the moisture incorporation into the system is minimized. These can be used as follows.

The acrylic pressure-sensitive adhesive has a co-polymer of (meth) acrylic acid alkyl ester obtained from (meth) acrylic acid with an aliphatic alcohol having 4 to 18 carbon atoms, and also the (meth) acrylic acid ester and other functional monomers thereof. Copolymers 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 and lauryl acryl Laterate, stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl acrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate, 2- Ethylhexyl methacrylate, isooctyl methacrylate, lauryl methacrylate, stearyl methacrylate and the like.

As said functional monomer, the monomer which has a hydroxyl group, the monomer which has a carboxyl group, the monomer which has an amide group, the monomer which has an amino group, etc. can be used. Examples of the monomer having a hydroxyl group include hydroxy alkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxylpropyl (meth) acrylate, and examples of the monomer having a carboxyl group include acrylic acid and methacrylic acid. -β unsaturated carboxylic acid; Maleic acid monoalkyl esters such as butyl maleate; Maleic acid; Fmarinic acid; Crotonic acid and the like.

Maleic anhydride can also obtain a (co) polymer of the same type as maleic acid.

As a monomer which has an amide group, Alkyl (meth) acrylamide, such as acrylamide, dimethyl acrylamide, and diethyl acrylamide; Alkyl ethyl methyl, such as butoxymethyl acrylamide and ethoxy methyl acrylamide (meth) acrylamide, diacetone acrylamide; Vinylpyrrolidone and the like. Examples of the monomer having an amino group include dimethylamino acrylate.

Copolymer monomers other than those described above include vinyl acetate, styrene, α-methylstyrene, vinyl chloride, acrylonitrile, ethylene, propylene, butadiene and the like, and copolymers with these also exhibit good properties.

It is preferable that (meth) acrylic-acid alkylester is contained in an adhesive as 50 weight% or more 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. may be used. The silicone resin pressure sensitive adhesive is preferably one in which 40% by weight of polydimethylsiloxane resin is crosslinked with 60% by weight of silicate rubber.

Among the pressure-sensitive adhesives, various compounding agents such as rosin-based resins, polyterpene-based resins, coumar indene-based resins, petroleum-based resins, and tefrenphenol-based resins may be used as necessary; Plasticizer layering agents, such as liquid lollybutene, mineral oil, lanolin, liquid polyisoprene, and liquid polyacrylate, and an antioxidant are added.

The structure of the matrix preparation according to the present invention is as follows.

As the exposed portion protective layer 1, an aluminum coated polyethylene terephthalate film or ethylene vinyl acetate or a soft film such as polypropylene, polyethylene, polyurethane, or polyvinyl chloride, which is difficult to permeate air and moisture, may be used. The containing and adhesive layer 2 is composed of a main drug component, a skin absorption enhancer, a drug stabilizer, a skin side effect alleviator, and the like as a main content layer by mixing a hydrophobic medical adhesive, a polyester film or paper coated with silicone or fluorine, A polyethylene terephthalate film or the like is used to attach the preparation to the skin so that the attachment site protective layer 6 is added to make the structure integrally made.

The structure of the reservoir preparation is controlled by the exposure site protective layer (1), the content-containing layer (3) made by combining a main drug component, a skin absorption enhancer, a drug stabilizer, and a skin side effect alleviator with an in-situ drug dissolving agent (3), and a drug release rate. As the microporous membrane layer 4 and the skin adhesive layer 5, a hydrophobic medical adhesive may be used alone or in combination with a hydrophobic medical adhesive such as a drug, a skin absorption enhancer, a drug stabilizer, and a skin side effects relieving agent. It is a structure made integrally by adding the attachment site protective layer 6 here.

The preparation method of the matrix preparation according to the present invention is as follows.

0.1 to 30% by weight of a single or mixture of drugs having a whitening action on the skin, 0.1 to 30% by weight of a single substance or mixture of the above, which can enhance the skin absorption of the drug, and a weak acid as a drug stabilizer. 0.01% to 2% by weight of a single substance or a mixture thereof, 0.01% to 10% by weight of a substance which can be used as an alleviator for skin side effects alone, or a mixture, and 0.1 to 20% by weight of hexane or After uniformly dispersing in an organic solvent such as ethyl acetate or chloroform, 8 to 99.68% by weight of a hydrophobic adhesive which can be used for medical purposes is added, and then stirred for at least 1 hour to stop stirring when the mixed solution is dispersed in a uniform state. Allow to stand at room temperature for a suitable time to remove bubbles.

The mixed solution is applied to silicon or fluorine coated paper or polyethylene terephthalate film using an applicator with a uniform thickness of 10 to 200 μm, and then left at room temperature for at least 1 hour to volatilize and remove the solvent. At this time, if necessary, after drying at room temperature can be dried for 10 minutes in a hot air dryer at 80 ℃.

After confirming that the solvent is sufficiently dried, the film is laminated using a soft material such as aluminum coated polyethylene terephthalate film, ethylene vinyl acetate or polypropylene, which is difficult to permeate air and moisture. At this time, if necessary, several layers with different prescriptions may be laminated in a multi-layered structure to adjust the skin absorption rate of the drug.

This is aged for 12 to 24 hours in a 37 ° C. thermostat, then cut into a shape that is easy to stick to the application site and finally formulated to an area of 0.1 to 500 cm 2.

The preparation method of a storage tank preparation according to the present invention is as follows.

After dissolving the hydrophobic medical pressure-sensitive adhesive in a suitable organic solvent, it is applied to a silicon or fluorine-coated paper or polyethylene terephthalate film using an applicator with a uniform thickness of 10 ~ 200㎛, and left at room temperature for at least 1 hour Volatilize and remove. At this time, if necessary, after drying at room temperature can be further dried for 10 minutes in a hot air dryer of 80 ℃. After confirming that the solvent is sufficiently dried, a microporous membrane made of a material such as polyethylene, polypropylene, ethylene vinyl acetate or the like is laminated thereon.

0.1 to 30% by weight of a single or mixture of drugs having a whitening action on the skin, 0.1 to 30% by weight of a single substance or mixture of the above, which can enhance the skin absorption of the drug, and a weak acid as a drug stabilizer. 0.01 to 2% by weight of a single substance or a mixture thereof, 0.01 to 10% by weight of a substance which can be used as an alleviator for skin side effects alone or in a mixture, and 28 to 99.78% by weight of a drug dissolving agent alone or mixed Stir to disperse the contents evenly.

In the exposed portion protective layer of the metal-coated plastic material of the type shown in FIG. 2, a predetermined amount of the above-mentioned dispersion is contained, and the skin adhesion layer and the attachment site protective layer laminated with the microporous membrane are laminated thereon, and the edges around the contents Seal the part with heat.

The final formulation is made by varying the area attached to the skin to 0.1 to 500 cm 2. In the transdermal absorption preparation for skin whitening according to the present invention, the transdermal absorption rate per unit time and unit area of the main drug component is preferably 0.01 to 50 µg.

The following examples and test examples illustrate the contents of the present invention. It is noted that the content of the present invention is not limited thereto.

Examples 1-20 are the contents and prescription prepared by the manufacturing method of a matrix type | mold formulation, and Examples 21-24 are the contents prescription example prepared by the manufacturing method of a reservoir type preparation.

Test examples for the transdermal penetration rate, efficacy, stability and skin safety using the animal skin of the skin-absorbing non-absorbing preparation for skin whitening prepared by the above-described method according to the formulation of each embodiment are as follows.

(Test Example 1)

The abdominal hair of a male guinea pig, weighing about 350 g, is shaved with a hair clipper, cut off at certain parts, stored frozen (less than -20 ° C), and dissolved in the test. After the skin is placed in the middle of the Franz-type glass diffuser with the stratum corneum part facing upwards, 50 vol% aqueous solution of glycerin is placed in the subspace and the temperature of the diffuser is maintained at 37 ° C. The percutaneous absorption formulation prepared in the formulation of each example is attached to the skin while the receptor solution is stirred at a constant speed (600 rpm).

At this time, the preparation is prepared in a circular shape to be 25 cm 2. After a certain period of time, collect the solution from the receptor section and replenish the amount of buffer solution. The collected sample is measured by concentration of each drug using high pressure liquid chromatography (HPLC).

The transdermal penetration rates of each drug calculated from the concentration analysis are shown in Table 1.

Table 1. Test penetration test result of percutaneous absorption type drug containing cosmetics for each skin whitening and cosmetics

As shown in Table 1, the percutaneous absorption type preparations prepared by the respective formulations containing ascorbic acid and its derivatives showed higher penetration rates than the general cosmetics.

(Test Example 2.)

Twenty healthy male and female experimenters were selected to select 2 × 2㎠ sites in the lower arm. Put aluminum foil on the arm so that ultraviolet rays are irradiated only on the test target area, and at the same time, two consecutive FL20S BLB lamps and FL 20S E-30 lamps manufactured by Toshiba, Japan, at a distance of 10 cm may be used at the same time. Three investigations were made.

The subject area was washed well with 70% aqueous isopropyl solution before irradiation.

After irradiation, each skin whitening drug 3% cosmetics were applied twice a day to the UV irradiation site, and the percutaneous absorption preparations prepared by the above example prescriptions were attached once a day, and then each test group was applied. The degree of suppression of color tone deposition was evaluated in three stages of remarkable effect, effectiveness and invalidity.

The results are shown in Table 2.

Table 2. Effectiveness test results of drug-containing transdermal absorption preparations and cosmetics for skin whitening

As shown in Table 2, the percutaneous absorption type preparations prepared by the formulations of Examples containing ascorbic acid and its derivatives showed higher positive effects than effective than cosmetics, and thus exhibited excellent color deposition inhibitory effect.

(Test Example 3)

The skin-containing cosmetics containing 3% of each skin whitening drug and the percutaneous absorption preparations prepared in the respective Examples were left in a 50 ° C thermostat for 2 months, and then the drug was extracted using a metalol, followed by high pressure liquid chromatography (HPLC). The results of measuring the titer of each product are shown in Table 3 below.

Table 3. Activity test results of drug-containing transdermal absorption preparations and cosmetics for skin whitening

As shown in Table 3, it was shown that the transdermal absorption preparations prepared by the respective formulations containing ascorbic acid and its derivatives showed superior stability by showing higher titers than cosmetics.

(Test Example 4.)

The percutaneous absorption preparation prepared by the above-described prescriptions of each Example 2 cm2 was cut into the lower arm of 20 healthy male and female experimenters 1 times a day, and a cosmetic containing 3% of the skin whitening drug was applied twice a day. After covering the outside with a metal cap, after 1 day, after 3 days, 7 days after observing the degree of stimulation according to the following determinations, the average is calculated.

Table 4. Skin safety test results of drug-containing transdermal absorption patches and cosmetics for skin whitening

As shown in Table 4, the skin side effects of the transdermal absorption preparations prepared by each example formulation with alpha bisabolol were dropped to a level almost similar to cosmetics.

Claims (4)

Ascorbyl and its derivatives, kojic acid and its derivatives, glycosamines, hydroquinone and its derivatives, compounds having a -SH group, butylhydroxytoluene (BHT), butylhydroxyanison (BHA), and the like. The percutaneous absorbent preparation is characterized by a matrix structure or a storage tank structure comprising a main content layer of a mixture of at least one drug having a tyrosinase inhibitory activity selected from the group consisting of a hydrophobic adhesive and a main content layer. 0.1-30% by weight of the above-mentioned drug component and 8-99.68% by weight of hydrophobic adhesive, 0.1-30% by weight of drug skin absorption enhancer 0.01-2% by weight of drug stabilizer, 0.1-20% by weight of drug solubilizer in system and 0.1% of skin side effects It is a mixture of ~ 10% by weight, characterized in that the hydrophobic pressure-sensitive adhesive is an acrylic polymer adhesive, a silicone pressure-sensitive adhesive or a rubber-based adhesive A method for improving the stability of a drug having tyrosinase inhibitory activity. The copolymer of (meth) acrylic acid alkyl ester and (meth) acrylic acid ester and other functional monomers according to claim 1, wherein the acrylic polymer adhesive is obtained by copolymerization of a C4-18 aliphatic alcohol with (meth) acrylic acid. And a copolymer with. The copolymer of the alkyl (meth) acrylic acid ester is butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl atryl acrylate, isooctyl acrylate, decyl acrylate, Isodecyl acrylate, lauryl acrylate, stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl acrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, It is at least 1 type selected from decyl methacrylate, isodecyl methacrylate, lauryl methacrylate, and stearyl methacrylate, As said functional monomer, 2-hydroxyethyl (meth) as a monomer which has a hydroxyl group is mentioned. Hydroxyalkyl (meth) acrylates, such as acrylate and hydroxypropyl (meth) acrylate .; As a monomer which has a carboxyl group, Monoalkyl esters of maleic acid, such as (alpha)-(beta) unsaturated carboxylic acid, such as acrylic acid and methacrylic acid, and butyl maleate, maleic acid, fmarinic acid, a crotonic acid; As a monomer which has an amide group, Alkyl ethyl ethyl methylol (meth) acrylamide, such as alkyl (meth) acrylamide, such as acrylamide, dimethyl acrylamide, and ethyl ethyl acrylamide, butoxymethyl acrylamide, and methoxymethyl acrylamide, Diacetone acrylamide; Vinylpyrrolidone; The monomer having an amino group is at least one selected from dimethylaminoacrylate, and the copolymer monomer is at least one selected from vinyl acetate, styrene, α-methylstyrene, vinyl chloride, acrylonitrile, ethylene, propylene and butadiene. How to. According to claim 1, wherein the rubber-based pressure-sensitive adhesive is a natural rubber, polyisoprene, polyisobutylene, polyvinyl ether, polyurethane, polybutadiene, styrene-butadiene polymer, styrene-isoprene copolymer, styrene-isoprene-butylene At least one selected from block copolymers; The silicone resin-based pressure-sensitive adhesive is a method in which 40% by weight of polydimethylsiloxane resin is crosslinked with 60% by weight of silicate rubber.