JP2003081815A - Skin-treating preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin-treating preparation which can promote the transdermal absorption of a medicine in a transdermal absorption preparation and substantially suppress skin irritation, when the transdermal absorption preparation is preliminarily adhered to the target skin and then peeled to apply the transdermal absorption preparation to the skin. SOLUTION: This skin-treating preparation is characterized by (1) having an adhesive layer formed to one side of a support, (2) containing an adhesive and 0.5 to 30 wt.% of a skin irritation-reducing agent in the adhesive layer, (3) having a 180 degree peel adhesion of >=1.4 N/10 mm to a stainless steel plate, measured according to JIS Z 0237, (4) having a 180 degree peel adhesion of <=0.7 N/10 mm, after adhered to the skin for >=12 hrs, and (5) having a horny peeling area ratio of >=70%, when adhered to the skin for >=12 hrs and then peeled.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method of applying a drug in the above-mentioned preparation when the above-mentioned preparation is applied to the skin by applying it on the skin to which the percutaneously absorbable preparation is applied in advance and then peeling it off. The present invention relates to a skin treatment preparation used for promoting percutaneous absorption.

[0002]

2. Description of the Related Art A percutaneous absorption preparation is applied to the skin for the purpose of absorbing a drug from the skin into the body. At the time of this percutaneous absorption, the following methods have been conventionally used to improve the absorption amount (Drug Deliv).
ery System 15-6, 2000, p492
-). A method of incorporating a percutaneous absorption enhancer in a percutaneous absorption preparation.
This method is a simple method and various studies have been conducted, but it is difficult to balance drug absorption and skin irritation due to the easy occurrence of skin irritation caused by a percutaneous absorption enhancer. There is. A highly absorbable prodrug method in which a drug with low absorbability is chemically modified to enhance absorbency and change into a structure with activity at the site of action. This method has a problem in that detailed studies on the dynamics and safety of prodrugs are required. A method of promoting absorption using electrical energy or ultrasonic energy. For example, in iontophoresis, an electrode is provided at the attachment site, and when an electric potential difference is applied, electroosmotic pressure is generated and the ionic drug is absorbed as a solvent flow is generated. Also, in sonophoresis, it is said that by sonicating the skin surface, micropores are created in the corneum, and a drug permeation pathway is created to improve the amount of permeation. Although some of them significantly improve the permeability depending on the drug, there is a problem that a complicated device is required and clinical application is difficult. A method in which a drug in a transdermal preparation is made into a supersaturated dissolution system. In this case, the drug permeation amount increases, but it is difficult to stably maintain the supersaturated state, which may cause a problem in formulation.

Further, the adhesive tape having an adhesive layer formed on one side of a support is pre-applied to the skin to which the transdermal absorption preparation is to be applied, and the peeling step is repeated, whereby the skin is removed. It is known that the horny layer of the skin is removed to some extent (stripping) and the percutaneous absorption is enhanced. However, if the keratin is exfoliated by this method, exfoliation will occur after the transdermal absorption preparation is applied to the skin. Skin irritation usually occurs due to physical damage from pulling over time and the protective response of the layers below the epidermal cell layer due to the loss of the barrier layer. Therefore, this method has never been used when actually applying a transdermal therapeutic preparation for treatment.

Further, in a transdermal absorption preparation such as a tape preparation in which a drug-containing pressure-sensitive adhesive layer is formed on one side of a support, skin irritation such as rash when applied (attached) to the skin is minimized. Is required. In order to reduce skin irritation in this case, there are mainly the following methods. By increasing the air permeability (moisture permeability) of the preparation, stuffiness during application is suppressed (see, for example, JP-A-6-271461). By reducing the adhesive strength of the adhesive, damage to the keratin during peeling after application to the skin is suppressed (Basic and Clinical Vol.26.
No. 14 p. 5277-5289, 1992). The above method has the effect of reducing the load on the skin during application, but has a limit in reducing skin irritation, and was insufficient to suppress irritation due to peeling. In addition, there is a problem that it is difficult to apply to a highly volatile drug in order to increase the air permeability. Further, the above method has an effect of suppressing irritation after peeling, but during application, a part of the patch may float from the skin, or in some cases, all may peel off.
There was a problem that it did not serve the purpose of treatment.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and the above-mentioned preparation is prepared by applying the transdermal preparation on the skin to which it is applied in advance and then peeling it off. It is an object of the present invention to provide a preparation for skin treatment, which can promote percutaneous absorption of a drug in the above preparation when applied to the skin and substantially suppress skin irritation.

[0006]

The invention according to claim 1 (hereinafter referred to as the present invention 1) is affixed in advance to the skin to which the percutaneous absorption preparation is applied, and then peeled off,
A skin treatment preparation for promoting percutaneous absorption of a drug in the preparation when the preparation is applied to the skin, comprising: (1) an adhesive layer formed on one surface of a support, (2) The pressure-sensitive adhesive layer contains a pressure-sensitive adhesive and a skin irritation reducing agent in a proportion of 0.5 to 30% by weight, and (3) JIS Z 0
1 for stainless steel plate, measured according to 237
80 degree peeling adhesive strength is 1.4N / 10mm or more,
(4) 180 degree peeling adhesive strength after adhering to skin for 12 hours or more is 0.7 N / 10 mm or less, (5) Exfoliation area ratio of keratin when peeling off after adhering to skin for 12 hours or more is 70% The above is characterized.

The skin treatment preparation according to the second aspect of the present invention (hereinafter referred to as the present invention 2) is the skin treatment preparation of the first present invention, further comprising an adhesive layer and the above-mentioned percutaneous absorption preparation. It is characterized in that it contains 0.1 to 30% by weight of the same drug as the drug contained in.

The pressure-sensitive adhesive used in the present invention is not particularly limited as long as it exhibits the pressure-sensitive adhesive properties specified in the present invention and is used for medical purposes. It is desirable that the drug that is added as needed is stable even after transfer to the skin. Examples of such an adhesive include acrylic-based, rubber-based, silicon-based, and urethane-based adhesives.

Examples of the acrylic pressure-sensitive adhesive include pressure-sensitive adhesives mainly composed of polyalkyl (meth) acrylate obtained by copolymerization of alkyl (meth) acrylate, which are copolymerizable with alkyl (meth) acrylate. It may be a copolymer with a functional monomer or another vinyl monomer.

Examples of the alkyl (meth) acrylate include 2-ethylhexyl (meth) acrylate and dodecyl (meth) acrylate. Examples of the polyfunctional monomer include 1,6-hexane glycol dimethacrylate and tetraethylene glycol diacrylate, and examples of the other vinyl monomers include N-vinyl-2-pyrrolidone and vinyl acetate. Is mentioned.

Examples of the rubber-based pressure-sensitive adhesive include pressure-sensitive adhesives mainly composed of natural rubber, styrene-isoprene-styrene block copolymer, styrene-olefin-styrene block copolymer, etc. Generally, rosin and hydrogenated A tackifier such as rosin, rosin ester, terpene resin, terpene phenol resin, petroleum resin, coumarone resin, coumarone-indene resin is added.

If the amount of the pressure-sensitive adhesive in the pressure-sensitive adhesive layer is small, the adhesive properties will be poor, and if it is large, the effects of the skin irritation reducing agent and the drug added if necessary will be 20 to 20.
99.5% by weight is preferable, and 30 to 90% by weight is more preferable.

The skin irritation-reducing agent used in the present invention is not particularly limited as long as it is an additive which, in combination with the above-mentioned pressure-sensitive adhesive, exhibits the pressure-sensitive adhesive properties specified in the present invention. For example, stearic acid, Fatty acids such as palmitic acid, myristic acid, lauric acid and oleic acid, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, lanolin alcohol, aliphatic alcohols such as geraniol, polyethylene glycol, polyoxyethylene / polyoxypropylene glycol And other polyhydric alcohols.

Although the detailed mechanism of reducing the skin irritation of the skin irritation reducing agent is unknown, the substance having the above-mentioned adhesive property moves to the stratum corneum when applied to the skin, and its hardness (elasticity, viscosity) is reduced. It is thought to lower. Therefore, after the skin treatment preparation of the present invention is applied (pasted) to the skin and then peeled off, only the outermost surface of the keratin is peeled off, so that the skin is substantially prevented from being damaged. The barrier layer against drug absorption when the formulation is applied (attached) can be thinned. Moreover, it is considered that the permeation of the skin irritation reducing agent causes a structural change in the stratum corneum to increase the rate of penetration of the drug into the stratum corneum.

The amount of the skin irritation reducing agent in the pressure-sensitive adhesive layer is limited to 0.5 to 30% by weight, because if the amount is small, the effect is not exhibited, and if the amount is large, the sticking property deteriorates.
Is preferred.

The pressure-sensitive adhesive layer used in the present invention further comprises
If necessary, a plasticizer, an absorption promoter, a stabilizer, a filler, etc. may be contained. These are added in an appropriate amount according to the purpose. The above-mentioned plasticizer is added to the pressure-sensitive adhesive to control the sticking property thereof, but at the same time, the diffusion rate of the drug, which is added as needed, in the pressure-sensitive adhesive is increased, and the amount of drug absorbed into the skin is improved. In some cases, it has the effect of Examples of the plasticizer include hydrocarbons such as liquid paraffin, isopropyl myristate, glycerin monolaurate, diethyl sebacate and other fatty acids and esters of monohydric or polyhydric alcohols, petroleum oils such as alicyclic saturated hydrocarbon resins. System fats and oils,
Examples include oils and fats derived from natural products such as olive oil. The optimum amount of the plasticizer in the adhesive layer depends on the combination of the adhesive used and the drug added as needed, but if it is too small, the effect will not appear, and if it is too large, the sticking property will be adversely affected. Therefore, 0.5 to 30% by weight is preferable.

The above absorption enhancer has an effect of acting on the skin to enhance the skin permeability of a drug added as necessary, and it enhances the drug distribution to the skin and the drug diffusion in the skin. There are things that increase speed. In particular,
Examples include surfactants such as lauric acid diethanolamide, lauroyl sarcosine, polyoxyethylene alkyl ethers and polyoxyethylene alkylamines, and solubilizers such as dimethylformamide, N-methyl-2-pyrrolidone and crotamiton. These can be added within a range that does not deteriorate the adhesiveness and skin irritation.

The above-mentioned stabilizers are used to prevent oxidation and decomposition of drugs and other components added as necessary and prevent changes over time of the skin treatment preparation. For example, butylhydroxytoluene and sorbine. Acids, antioxidants such as sodium bisulfite, cyclodextrin, ethylenediaminetetraacetic acid and the like.

The above-mentioned filler is used for controlling the sticking property and for uniformly dispersing / holding the drug added if necessary. Specific examples include calcium carbonate, titanium oxide, lactose, crystalline cellulose, and silicic acid anhydride.

The skin treatment preparation of the present invention has a JIS Z
The 180 degree peeling adhesion to a stainless steel plate measured according to 0237 is limited to 1.4 N / 10 mm or more, and preferably 2.0 to 6.0 N / 10 mm. When the adhesive force is less than 1.4 N / 10 mm,
It becomes easy to peel off during application.

The skin treatment preparation of the present invention has a 180-degree peel strength of 0.7 after being applied to the skin for 12 hours or more.
It is limited to N / 10 mm or less, preferably 0.4 to
It is 0.7 N / 10 mm. The adhesive strength is 0.7N / 1
If it exceeds 0 mm, the adhesive force is too strong, and the skin is likely to be physically damaged. This measuring method is as follows. On the abdominal skin of the shaved animal, a skin treatment preparation (hereinafter referred to as a sample) cut into a size of 15 × 50 mm was applied parallel to the midline, and 12 hours or more after application,
The animal is anesthetized and fixed on a flat plate, and the sample is peeled from the head to the tail at a peeling angle of 180 ° and a peeling speed of 300 mm / min. Then, with respect to the lengthwise direction of the pasting surface of 45 mm (of the sample length of 50 mm, 5 mm is used as a gripping portion and is previously bonded to a gripping film or the like so as not to adhere to the skin) 15, 25, from the peeling start portion, The load at the position of 35 mm is recorded, and the average value is obtained.

The skin treatment preparation of the present invention has a keratin exfoliation area ratio of 70% or more when peeled off after being applied to the skin for 12 hours or more, and preferably 80 to 100%.
Is. When the area ratio is less than 70%, the effect of the present invention is not exerted because the keratin does not adhere sufficiently. This measuring method is as follows. The above-mentioned sample obtained by 180 ° peeling after sticking to animal skin was used as a dye (a solution consisting of 1.0% by weight of gentian violet, 0.5% by weight of brilliant green, and 98.5% by weight of distilled water).
The area of keratinocyte detachment area is measured in three visual fields using an image analyzer, and the average value is calculated.

In the skin treatment preparation of the present invention 2, the adhesive layer further contains the same drug as that contained in the percutaneously absorbable preparation. The amount of the drug in the pressure-sensitive adhesive layer is limited to the range of 0.1 to 30% by weight, because when the amount is small, the drug effect may not be exhibited, and when the amount is large, the sticking property may be deteriorated. Thus, when the above-mentioned drug is contained in the skin treatment preparation, the drug can be absorbed into the body simultaneously with the skin treatment by the skin treatment preparation.
When a transdermal preparation is applied, the total absorption amount of the drug can be increased.

The percutaneous absorption preparation used in the present invention is not particularly limited as long as it has a dosage form capable of percutaneously absorbing the drug, and for example, a patch containing the drug, an ointment,
Examples thereof include gel agents and lotions.

The drug contained in the percutaneous absorption preparation is not particularly limited as long as it is used for medical purposes.
For example, antihypertensive agents such as nifedipine and clonidine, vasodilators such as nitroglycerin and isosorbide nitrate, steroid hormone agents such as estradiol and progesterone, anesthetics such as lidocaine, anti-inflammatory analgesics such as indomethacin and ketoprofen, prednisolone, dexamethasone and the like. Steroidal anti-inflammatory drug, diphenhydramine,
Antihistamines such as chlorpheniramine, etc. may be mentioned.

The skin treatment preparation of the present invention has a pressure-sensitive adhesive layer formed on one side of a support, but as described above, the pressure-sensitive adhesive layer may contain a drug. Further, a drug holding layer (sometimes referred to as a reservoir layer) that holds a drug may be provided between the support and the adhesive layer. Further, the pressure-sensitive adhesive layer may contain microcapsules or fiber layers.

In the skin treatment preparation of the present invention, release paper is usually laminated on the surface of the pressure-sensitive adhesive layer in order to protect the pressure-sensitive adhesive layer until the time of application.

The material and constitution of the above-mentioned support are not particularly limited, but usually a film, a woven fabric, a non-woven fabric and a laminate of these are used. The material of the film is not particularly limited, and examples thereof include polyethylene, polypropylene, ethylene / vinyl acetate copolymer, ethylene / methyl (meth) acrylate copolymer, polyvinyl chloride, polyvinylidene chloride, polyurethane, nylon, polyester. , Styrene / isoprene / styrene block copolymer, styrene / ethylene / butylene / styrene block copolymer, and the like, and they can be used alone or as a blend.

The material of the above-mentioned woven fabric and non-woven fabric is not particularly limited, and examples thereof include polyethylene, polypropylene, ethylene / vinyl acetate copolymer, ethylene / methyl (meth) acrylate copolymer, nylon, polyester, styrene / isoprene. -Styrene block copolymers, styrene / ethylene / butylene / styrene block copolymers, rayon, cotton and the like can be mentioned, and they can be used alone or in a blend.

The thickness of the above-mentioned support varies depending on the material, but if it is too thin, the shape retention is insufficient and the patch is easily deformed, making it difficult to handle, and if it is too thick, the support becomes too stiff to be applied at the time of application. Since the ability to follow the skin is deteriorated and a feeling of strangeness is likely to occur, the film has a thickness of 5 to 200 μm, the woven and non-woven fabric has a thickness of 100 to 1000 μm, and the basis weight is 30 to 15
0 g / m ² is preferred.

The release paper is not particularly limited as long as it can protect the pressure-sensitive adhesive layer, but normally, a single layer such as film or paper or a laminate having the surface subjected to a release treatment is used. Examples of the material of the film include polyethylene terephthalate, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride and the like. Paper impregnated with a resin such as polyvinyl alcohol can also be used.

The method for producing the skin treatment preparation of the present invention is not particularly limited, but examples thereof include the following methods.

First, the adhesive and the skin irritation reducing agent (and
If necessary, an adhesive composition comprising a drug, a plasticizer, an absorption promoter, a stabilizer, an additive such as a filler) is prepared. The preparation of the pressure-sensitive adhesive composition may be carried out by a method of uniformly stirring and kneading each with a predetermined ratio using an ordinary stirring and kneading machine, and with respect to a predetermined amount of the pressure-sensitive adhesive prepared in advance. , A predetermined amount of the skin irritation reducing agent and each predetermined amount of one or more of the various additives that are added as necessary are added, and these are uniformly stirred by using an ordinary stirring and kneading machine. A method of kneading may be adopted.

Next, a pressure-sensitive adhesive layer made of the above-mentioned pressure-sensitive adhesive composition is formed on one surface of the support prepared in advance,
The desired skin treatment formulation can be produced.

The method for forming the pressure-sensitive adhesive layer on one surface of the support is not particularly limited, but for example, an ordinary coating machine is used to apply the pressure-sensitive adhesive composition to a predetermined surface of the support. Coating so that the thickness after drying will be a predetermined thickness, if necessary, through a step such as drying and cooling to form an adhesive layer, the release treated surface of the release paper on the surface of this adhesive layer A method of laminating (direct coating method) may be adopted, and the thickness after drying the pressure-sensitive adhesive composition on the release treated surface of the release paper becomes a predetermined thickness by using an ordinary coating machine. As described above, a method (transfer method) is used in which a pressure-sensitive adhesive layer is formed through steps such as drying and cooling as necessary, and the pressure-sensitive adhesive layer is laminated on a predetermined surface of the support and transferred. Is good, but because it is excellent in productivity,
It is preferable to adopt the latter transfer method.

Specific examples of the method for forming the pressure-sensitive adhesive layer include solvent coating method and hot melt coating method. As an example of the solvent coating method, a solvent solution or solvent dispersion of an adhesive composition is prepared, spread on a release paper (or support) surface, and the solvent is dried, and then a support (or release paper) is laminated. There is a method of doing. In addition, as an example of the hot melt coating method, usually, the pressure-sensitive adhesive layer constituents other than the drug are heated and stirred at a temperature of 100 to 150 ° C. under nitrogen substitution, and then dissolved.
Cool to a temperature of 100-120 ° C., add the drug and mix uniformly. Next, a method of spreading the obtained pressure-sensitive adhesive composition on the release paper (or support) surface with a hot melt coater and laminating the support (or release paper) can be mentioned.

The skin treatment preparation of the present invention is used by a method in which the transdermal preparation is applied in advance on the skin to be applied (applied) and then peeled off. The time from the attachment to the peeling is not limited, but is 8 to 24.
Time is preferred.

[0038]

[Function] The skin treatment preparation of the present invention is applied (pasted)
As a result, the contained skin irritation reducing agent penetrates into the stratum corneum of the skin during application, and lowers the hardness (elasticity and viscosity) of the stratum corneum. After that, when the skin treatment preparation is peeled off, only the outermost surface of the keratin is peeled off, so that it is possible to prevent drug damage when the percutaneous absorption preparation is applied (pasted) next while suppressing substantial damage to the skin. The barrier layer can be thinned.
Moreover, it is considered that the permeation of the skin irritation reducing agent causes a structural change in the stratum corneum to increase the rate of penetration of the drug into the stratum corneum. Furthermore, as described above, since the skin is less damaged by peeling, the occurrence of skin irritation when the transdermal absorption preparation is applied (attached) is substantially suppressed. Therefore, by using the skin treatment preparation of the present invention, it is possible to promote the percutaneous absorption of the drug in the percutaneous absorption preparation and substantially suppress the skin irritation.

[0039]

BEST MODE FOR CARRYING OUT THE INVENTION The following examples are given to illustrate the present invention in more detail, but the present invention is not limited to these examples.

In this example, the following raw materials were used. 1. Adhesive (1) Adhesive A: 2-ethylhexyl acrylate 13
92 g, 2-ethylhexyl methacrylate 11976
g, dodecyl methacrylate 1924 g, 1,6-hexane glycol dimethacrylate 19 g, ethyl acetate 5
103 g was placed in a 40 liter polymerization apparatus, heated to 80 ° C. under nitrogen substitution, and then 20 g of lauroyl peroxide dissolved in 500 g of cyclohexane and 1500 g of ethyl acetate was added thereto for 8 hours to carry out polymerization to obtain a polymer having a molecular weight of 1
An adhesive A solution having 140,000 and a solid content of 45% by weight was obtained.

(2) Adhesive B: 2-ethylhexyl acrylate 11764 g, vinylpyrrolidone 3500 g,
16 g of 1,6-hexane glycol dimethacrylate,
13600 g of ethyl acetate was placed in a polymerization apparatus of 40 liters and heated to 80 ° C. under nitrogen substitution, and then 15 g of lauroyl peroxide was added to 1200 g of cyclohexane and 80 g of ethyl acetate.
Polymerization was carried out while adding the solution dissolved in 0 g over 10 hours to obtain an adhesive B solution having a molecular weight of 580,000 and a solid content of 35% by weight.

2. Skin irritation reducing agent: (1) Stearic acid (2) Lauryl alcohol (3) Polyethylene glycol 1000 3. Drug: isosorbide dinitrate 4. Plasticizer: isopropyl myristate 5. Absorption enhancer: polyoxyethylene (9E.0) lauryl ether

6. Support: PET / EVA laminated film (polyethylene terephthalate 12 μm thick / ethylene / vinyl acetate copolymer resin 30 μm thick laminated film) 7. Release paper: Release PET film (polyethylene terephthalate film with a release treatment on one side with a silicone release agent)

Example 1 An appropriate amount of the adhesive A solution was taken, and lauryl alcohol was used as a skin irritation reducing agent, and isopropyl myristate was used as a plasticizer. 15% by weight, ethyl acetate was added to adjust the nonvolatile content to 25% by weight, and the mixture was uniformly kneaded with a dissolver to prepare a pressure-sensitive adhesive composition. Then, the release-treated surface of the release PET film had a thickness of 80 μm after the pressure-sensitive adhesive composition was dried.
It is coated with a knife coater to 30 m at 30 ° C at 60 ° C.
After drying for a minute to form a pressure-sensitive adhesive layer, this pressure-sensitive adhesive layer was laminated on the PET surface of a PET / EVA laminated film to produce a skin treatment preparation A1.

(Example 2) An appropriate amount of the adhesive B solution was taken, and stearic acid was used as a skin irritation reducing agent in a ratio of 8% by weight to 92% by weight of the nonvolatile content of the adhesive B, and ethyl acetate was added. To prepare a nonvolatile content of 25% by weight,
A pressure-sensitive adhesive composition was prepared by uniformly kneading and kneading with a dissolver. A skin treatment preparation B1 was produced in the same manner as in Example 1 except that this pressure-sensitive adhesive composition was used.

(Comparative Example 1) Example 1 was repeated except that lauryl alcohol was not added and the ratio of isopropyl myristate to 15% by weight to the nonvolatile content of 85% by weight of the pressure-sensitive adhesive A was adjusted. Same procedure as above for preparation A2 for skin treatment
Was manufactured.

Comparative Example 2 Polyoxyethylene (9E.0.) Lauryl ether was used as an absorption promoter without adding stearic acid, and polyoxyethylene (9E 0.0.) A skin treatment preparation B2 was produced in the same manner as in Example 2 except that the ratio of lauryl ether was 3% by weight.

(Reference Example) Production of percutaneous absorption preparation An appropriate amount of the adhesive B solution was taken, polyethylene glycol 1000 was used as a skin irritation reducing agent, and isosorbide dinitrate was used as a drug, based on 75% by weight of the nonvolatile content of the adhesive B. Take the ratio of 10% by weight and 15% by weight respectively,
Ethyl acetate was added to adjust the nonvolatile content to 25% by weight, and the mixture was uniformly kneaded with a dissolver to prepare a pressure-sensitive adhesive composition. A transdermal preparation was manufactured in the same manner as in Example 2 except that this pressure-sensitive adhesive composition was used.

Performance Evaluation The skin treatment preparations of Examples 1 and 2 and Comparative Examples 1 and 2 were evaluated for performance by the following method using samples cut into a size of 15 × 50 mm. Measurement of adhesive strength (180 degree peeling adhesive strength test for stainless steel plate): Measured according to JIS Z 0237. Measurement of peeling strength (180 degree peeling adhesiveness after sticking to skin for 12 hours or more): A sample was placed on the abdominal skin of a rat (Wistar system, male, 14 weeks old) that had been shaved with a clipper and shaver in advance. Attached parallel to the line. Twenty-four hours after application, the rat was fixed on a flat plate under pentobarbital anesthesia (intraperitoneal administration), and the sample was peeled from the head to the tail at a peeling angle of 180 degrees and a peeling speed of 300 mm / min. . Then, the lengthwise direction of the pasting surface is 45 mm (of the sample length of 50 mm, 5 m
For m), the load was recorded at a position of 15, 25, 35 mm from the peeling start part, and the average value was calculated.

Measurement of keratin peeling area ratio: The peeled sample used in the above peeling force measurement was dyed (gentian violet 1.0% by weight, brilliant green 0.5).
(A solution consisting of 9% by weight of distilled water and 98.5% by weight of distilled water), and then washed thoroughly with water. Then, the keratinocyte detachment area ratio was measured in three visual fields using an image analyzer, and the average value was calculated. Measurement of area ratio of peeling: Immediately before the above peeling force measurement, the area where the sample spontaneously peeled off during application was visually judged, and the ratio of the peeled area was judged at 10% intervals.

Measurement of the amount of drug transfer: In the above-mentioned peeling force measurement, 15 was applied to the skin immediately after peeling the samples of Examples 1 and 2 and Comparative Examples 1 and 2, and to the skin to which nothing was applied after shaving. A percutaneous absorption preparation cut into a size of 15 mm was applied. After 24 hours, the transdermal absorption preparation was peeled off, immersed in methanol, and the residual amount of the drug was measured by HPLC to calculate the amount of drug transferred to the skin. Measurement of skin irritation: The skin used in the measurement of the drug transfer amount was evaluated immediately after peeling and 24 hours later. The evaluation criterion is the Draize method (Fraiz method (1959 FDA, 1973 Federal Register
r)] according to the following criteria. Criteria for erythema formation No erythema 0 Very slight erythema (finally noticeable) 1 Clear erythema 2 Moderate to strong erythema 3 Light scab on strong deep red erythema 4

Regarding the number of repetitions of each of the above-mentioned tests, the number of repetitions was 5, except that the measurement of the adhesive strength was repeated 3, and the evaluation results are shown as the average value.

The results of the above-mentioned evaluations are shown in Table 1.

[0054]

[Table 1]

[0055]

The composition of the skin treatment preparation of the present invention is as described above. Using the skin treatment preparation of the present invention, it is applied in advance on the skin to which the transdermal preparation is applied, and then, By peeling, when the transdermal preparation is applied to the skin, the transdermal absorption of the drug in the transdermal preparation can be promoted and the skin irritation can be substantially suppressed.

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Claims (2)

[Claims] 1. A percutaneous absorption preparation is pre-applied on the skin to which it is applied, and then peeled off to promote percutaneous absorption of the drug in the preparation when the preparation is applied to the skin. A preparation for skin treatment, comprising (1) a pressure-sensitive adhesive layer formed on one surface of a support, and (2) the pressure-sensitive adhesive layer,
It contains an adhesive and a skin irritation reducing agent in a proportion of 0.5 to 30% by weight, and has a 180 degree peeling adhesion to a stainless steel plate measured in accordance with (3) JIS Z 0237: 1. 4 N / 10 mm or more, (4) 180 degree peeling after sticking to skin for 12 hours or more, adhesive strength is 0.7 N / 10 mm or less, (5) Keratin peeling when peeled off after sticking to skin for 12 hours or more Area rate is 70%
A skin treatment preparation characterized by the above. 2. The adhesive layer further contains the same drug as the drug contained in the percutaneous absorption preparation in an amount of 0.1 to 30% by weight. Preparation for skin treatment.