JP7216867B2 - Patches containing fentanyl - Google Patents

Description

The present invention relates to a fentanyl-containing patch.

Fentanyl is a compound classified as a synthetic opioid that acts as a highly selective full agonist at the mu opioid receptor and is intended for the relief of moderate to severe cancer pain, chronic pain, and postoperative pain. used as As a salt of fentanyl, it is used in the form of citrate.

Fentanyl-containing patches are expected to have the advantage of being easy to manage the blood concentration of fentanyl by attaching and detaching them, and many studies have been conducted from the viewpoint of skin irritation and skin permeability (for example, Patent Documents 1 to 3). 3). Fentos (registered trademark) tape, Wanduro (registered trademark) patch, and the like are commercially available as fentanyl-containing patches for once-daily administration (eg, Non-Patent Documents 1 and 2).

WO2009/051217 JP-A-10-45570 JP-A-11-302161

Fentos® Tape Package Insert (Revised 2016) Wanduro (registered trademark) patch package insert (revised 2018)

Since fentanyl is usually administered to patients with moderate to severe pain, it may be required to carefully control the blood concentration according to the patient's condition. However, the fentanyl-containing patch contains 0.2 mg or more of fentanyl citrate per 1 cm ² of patch area, and it may be difficult to finely control the blood concentration.

When the present inventors prepared a patch having a patch area of 2.5 cm ² and containing 0.5 mg of fentanyl citrate, they unexpectedly found that the storage stability of fentanyl citrate decreased. Found it.

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a patch having excellent storage stability even when the content of fentanyl or a salt thereof is low.

The present invention provides the following [1] to [14].
[1] A patch comprising an adhesive layer on a support, wherein the adhesive layer contains fentanyl or a salt thereof and an adhesive, and the content of fentanyl or a salt thereof in the adhesive layer is , 0.01 to 0.18 mg of fentanyl citrate per 1 cm ² of application area.
[2] The patch of [1], which is a tape.
[3] The patch of [1] or [2], wherein the content of fentanyl or a salt thereof in the adhesive layer is 0.1-0.8 mg in terms of fentanyl citrate.
[4] The patch according to any one of [1] to [3], which has a patch area of 3 to 10 cm ² .
[5] The patch of any one of [1] to [4], wherein the concentration of fentanyl or its salt is 0.5 to 3.8% based on the weight of the entire adhesive layer.
[6] The patch of any one of [1] to [5], wherein the adhesive layer further contains a plasticizer.
[7] The patch according to any one of [1] to [6], wherein the adhesive layer further contains a tackifying resin.
[8] A patch comprising an adhesive layer on a support, wherein the adhesive layer contains fentanyl or a salt thereof and an adhesive, and the concentration of fentanyl or a salt thereof in the adhesive layer is A patch containing 0.5 to 3.8% in terms of mass of fentanyl citrate.
[9] The patch of [8], which is a tape.
[10] The patch of [8] or [9], wherein the content of fentanyl or a salt thereof in the adhesive layer is 0.1-0.8 mg in terms of fentanyl citrate.
[11] The adhesive patch according to any one of [8] to [10], having an adhesive area of 3 to 10 cm ² .
[12] The patch of any one of [8] to [11], wherein the concentration of fentanyl or its salt is 0.5 to 3.8% based on the weight of the entire adhesive layer.
[13] The patch of any one of [8] to [12], wherein the adhesive layer further contains a plasticizer.
[14] The patch of any one of [8] to [13], wherein the adhesive layer further contains a tackifying resin.

According to the present invention, even if the content of fentanyl or a salt thereof is low (for example, even if the content of fentanyl or a salt thereof is 0.1 to 0.8 mg in terms of fentanyl citrate). , a patch having excellent storage stability of fentanyl or a salt thereof can be provided.

As used herein, the term "storage stability" means that 95% or more of fentanyl or its salt remains in its original form after a patch containing fentanyl or its salt is stored for a certain period of time. . "Excellent storage stability" means that, for example, after storing a patch containing fentanyl citrate at 60°C for 1 month (severe test), the content of fentanyl citrate before storage is at least 95%.

The present invention is described in detail below.

One embodiment of the present invention is a patch comprising an adhesive layer on a support, wherein the adhesive layer contains fentanyl or a salt thereof and an adhesive, and the adhesive layer contains fentanyl or a salt thereof. The patch contains 0.01 to 0.18 mg of fentanyl citrate per 1 cm ² of patch area.

In the patch according to this embodiment, the adhesive layer contains fentanyl or a salt thereof and an adhesive.

Fentanyl is also called N-(1-phenethylpoperidin-4-yl)-N-phenylpropanamide. A salt of fentanyl means an acid addition salt of fentanyl, specifically a salt of fentanyl and an organic acid or an inorganic acid. Organic acids include, for example, acetic acid, lactic acid, citric acid, oxalic acid, maleic acid, fumaric acid, glutamic acid, aspartic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and toluenesulfonic acid. Inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. A preferred fentanyl or salt thereof is fentanyl citrate.

In this specification, when calculating the content or concentration of fentanyl or its salt, it is considered in terms of fentanyl citrate. Fentanyl citrate is a monocitrate of fentanyl represented by the chemical formula (1) and has a molecular weight of 528.59.

As used herein, "fentanyl or its salt content in the adhesive layer" means the content of fentanyl or its salt contained in the entire adhesive layer of the patch. It is considered in terms of the mass of the acid salt.

In the patch according to the present embodiment, the content of fentanyl or a salt thereof in the adhesive layer is preferably 0.1 to 0.8 mg when converted to the mass of fentanyl citrate, and 0.2 mg. ~0.7 mg is more preferred, and 0.4 to 0.65 mg is particularly preferred.

In addition, the "application area" means the area that comes into contact with the skin when the patch is applied to the skin. The patch according to the present embodiment preferably has a patch area of 3 to 10 cm ² , more preferably 4 to 8 cm ² . When the application area is 3 cm ² or more, the handleability is further improved and the application is easy. When the application area is 10 cm ² or less, the periphery of the patch is less likely to be caught when putting on or taking off clothes.

“Fentanyl or its salt content per 1 cm ² of application area” means the content of fentanyl or its salt in the adhesive layer corresponding to 1 cm ² of the area in contact with the skin, and in the present invention, fentanyl citrate It is considered in terms of the mass of the acid salt. That is, the content of fentanyl or a salt thereof may be a value obtained by converting the content of fentanyl or a salt thereof contained in the pressure-sensitive adhesive layer into the mass of fentanyl citrate and then dividing it by the application area.

In the patch according to the present embodiment, the content of fentanyl or a salt thereof per 1 cm ² of the patch area is preferably 0.01 to 0.18 mg, more preferably 0.01 to 0.09 mg, More preferably 0.02 to 0.08 mg, particularly preferably 0.03 to 0.07 mg.

As used herein, "concentration of fentanyl or a salt thereof" means the mass of fentanyl or a salt thereof based on the mass of the entire pressure-sensitive adhesive layer. considered in terms of conversion.

In the patch according to the present embodiment, the concentration of fentanyl or a salt thereof in the adhesive layer is preferably 0.5 to 3.8% when converted to the mass of fentanyl citrate, and is preferably 0.5%. It is more preferably ∼3.5%, and particularly preferably 1 to 2.5%.

Any pressure-sensitive adhesive may be used as long as it is commonly used for patches, and examples thereof include acrylic pressure-sensitive adhesives, rubber-based pressure-sensitive adhesives, and silicone-based pressure-sensitive adhesives. A preferred adhesive is a rubber-based adhesive.

Examples of acrylic pressure-sensitive adhesives include polymers of (meth)acrylic acid alkyl esters and copolymers of (meth)acrylic acid alkyl esters and comonomers. Here, (meth)acrylic acid alkyl ester means acrylic acid alkyl ester and methacrylic acid alkyl ester. Examples of (meth)acrylic acid alkyl esters include butyl (meth)acrylate, isobutyl (meth)acrylate, hexyl (meth)acrylate, octyl (meth)acrylate, 2-ethylhexyl (meth)acrylate, and ( meth)decyl acrylate. The (meth)acrylic acid alkyl esters may be used alone or in combination of two or more. Comonomers include, for example, hydroxyalkyl (meth)acrylates, ethylene, propylene, styrene, vinyl acetate, N-vinylpyrrolidone, and (meth)acrylic acid amides. A comonomer may be used individually or in combination of 2 or more types. Specific examples of acrylic adhesives include copolymers containing at least two selected from butyl acrylate, 2-ethylhexyl acrylate, vinyl acetate, methacrylic acid, hydroxyethyl acrylate, glycidyl methacrylate, methoxyethyl acrylate, and acrylic acid. More specifically, DURO-TAK 87-2097, 87-2194, 87-2196, 87-2287, 87-2516, 87-2852, 87-4287, and 87-900A (trade name , manufactured by Henkel), and Nisset KP-77 and AS-370 (trade names, manufactured by Nippon Carbide Industry Co., Ltd.).

Examples of rubber adhesives include styrene-isoprene-styrene copolymer (SIS), isoprene rubber, polyisobutylene (PIB), styrene-butadiene-styrene block copolymer (SBS), and styrene-butadiene rubber (SBR). , polysiloxane, and the like. These rubber pressure-sensitive adhesives may be used singly or in combination of two or more. A preferred rubber adhesive is styrene-isoprene-styrene copolymer (SIS) or polyisobutylene (PIB). Specific examples of rubber adhesives include Oppanol B12, B15, B50, B80, B100, B120, B150, B220 (trade name, manufactured by BASF), JSR Butyl 065, 268, 365 (trade name, manufactured by JSR). , Vistanex LM-MS, MH, H, MML-80, 100, 120, 140 (trade name, manufactured by Exxon Chemical), HYCAR (trade name, manufactured by Goodrich), Quintac 3570C (trade name, Nippon Zeon company), SIS5002 (trade name, manufactured by JR Kraton Elastomer), SIBSTAR T102 (trade name, manufactured by Kaneka Corporation), and the like.

Examples of silicone-based adhesives include organopolysiloxanes such as dimethylpolysiloxane and condensation reaction products of dimethylpolysiloxane and silicate resins. Specific examples of silicone adhesives include BIO-PSA X7-4201, BIO-PSA 7-4102, BIO-PSA 7-4202, BIO-PSA 7-4302, BIO-PSA Q7-4501, 360 Medical fluid 1000CS, and MDX4-4210 (trade name, manufactured by Dow Corning) can be mentioned.

The content of the adhesive is preferably 10 to 95% by mass, more preferably 10 to 80% by mass, based on the mass of the entire adhesive layer.

The pressure-sensitive adhesive layer may further contain, as other components, a tackifying resin, a plasticizer, a percutaneous absorption enhancer, a stabilizer, a filler, a fragrance, and the like.

Examples of the tackifying resin include rosin derivatives such as rosin, glycerol ester of rosin, hydrogenated rosin, glycerol ester of hydrogenated rosin and pentaerythritol ester of rosin, Alcon P100 (trade name, manufactured by Arakawa Chemical Industries, Ltd.), and the like. Alicyclic saturated hydrocarbon resins, aliphatic hydrocarbon resins such as Quinton B170 (trade name, manufactured by Nippon Zeon Co., Ltd.), terpene resins such as Clearon P-125 (trade name, manufactured by Yasuhara Chemical Co., Ltd.), maleic acid resins, etc. mentioned. Among these, glycerin esters of hydrogenated rosin, alicyclic saturated hydrocarbon resins, aliphatic hydrocarbon resins and terpene resins are preferred, and alicyclic hydrocarbon resins are more preferred. Two or more of these tackifying resins may be combined. By containing a tackifying resin, the adhesiveness of the pressure-sensitive adhesive layer can be improved and other physical properties can be stably maintained.

The content of the tackifying resin is preferably 0 to 80% by mass, more preferably 10 to 70% by mass, based on the total mass of the adhesive layer.

Plasticizers include, for example, petroleum oils such as paraffinic process oils, naphthenic process oils and aromatic process oils; squalane; squalene; vegetable oils such as olive oil, camellia oil, castor oil, tall oil and peanut oil; silicone oil; dibasic acid esters such as dibutyl phthalate and dioctyl phthalate; liquid rubbers such as polybutene and liquid isoprene rubber; liquid fatty acid esters such as isopropyl myristate, hexyl laurate, diethyl sebacate and diisopropyl sebacate; glycol; glycol salicylate; propylene glycol; dipropylene glycol; triacetin; triethyl citrate; Among these, liquid paraffin, liquid polybutene, isopropyl myristate, diethyl sebacate and hexyl laurate are preferred, liquid polybutene, isopropyl myristate and liquid paraffin are more preferred, and liquid paraffin is particularly preferred. Two or more of these plasticizers may be combined.

The percutaneous absorption enhancer may be any compound that is conventionally known to have a percutaneous absorption enhancing effect on the skin. Percutaneous absorption enhancers include, for example, organic acids and salts thereof (eg, aliphatic carboxylic acids having 6 to 20 carbon atoms (hereinafter also referred to as "fatty acids") and salts thereof, cinnamic acid and salts thereof). , organic acid esters (e.g., fatty acid esters, cinnamic acid esters), organic acid amides (e.g., fatty acid amides), fatty alcohols, polyhydric alcohols, ethers (e.g., fatty ethers, polyoxyethylene alkyl ethers), etc. . These absorption enhancers may have unsaturated bonds and may have cyclic, linear or branched chemical structures. Transdermal absorption enhancers may also be monoterpene-based compounds, sesquiterpene-based compounds, and vegetable oils (eg, olive oil). Two or more of these percutaneous absorption enhancers may be combined.

Such organic acids include aliphatic (mono-, di- or tri)carboxylic acids such as acetic acid, propionic acid, citric acid (including anhydrous citric acid), isobutyric acid, caproic acid, caprylic acid, fatty acids, lactic acid, maleic acid , pyruvic acid, oxalic acid, succinic acid, tartaric acid, etc.), aromatic carboxylic acids (e.g., phthalic acid, salicylic acid, benzoic acid, acetylsalicylic acid, etc.), cinnamic acid, alkanesulfonic acids (e.g., methanesulfonic acid, ethanesulfone acid, propanesulfonic acid, butanesulfonic acid), alkylsulfonic acid derivatives (e.g. polyoxyethylene alkyl ethersulfonic acid, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid), cholic acid derivatives (e.g. dehydrocholic acid, etc.). These organic acids may be alkali metal salts such as sodium salts. Among them, aliphatic carboxylic acids, aromatic carboxylic acids or salts thereof are preferred, and acetic acid, sodium acetate or citric acid is particularly preferred.

Examples of fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid and linolenic acid.

Examples of organic acid esters include ethyl acetate, propyl acetate, cetyl lactate, lauryl lactate, methyl salicylate, ethylene glycol salicylate, methyl cinnamate, and fatty acid esters. Examples of fatty acid esters include methyl laurate, hexyl laurate, isopropyl myristate, myristyl myristate, octyldodecyl myristate, and cetyl palmitate. The fatty acid ester may be glycerin fatty acid ester, propylene glycol fatty acid ester, sorbitan fatty acid ester, polyethylene glycol sorbitan fatty acid ester, polyethylene glycol fatty acid ester, sucrose fatty acid ester, or polyoxyethylene hydrogenated castor oil. Specific examples of fatty acid esters include glycerin monocaprylate, glycerin monocaprate, glycerin monolaurate, glycerin monooleate, sorbitan monolaurate, sucrose monolaurate, polysorbate 20 (trade name), and propylene glycol monolaurate. rate, polyethylene glycol monolaurate, polyethylene glycol monostearate, Span 20, Span 40, Span 60, Span 80, Span 120 (trade name), Tween 20, Tween 21, Tween 40, Tween 60, Tween 80 (trade name), NIKKOL HCO-60 (trade name, manufactured by Nikko Chemicals Co., Ltd.).

Examples of organic acid amides include fatty acid amides (eg, lauric acid diethanolamide), hexahydro-1-dodecyl-2H-azepin-2-one (also referred to as Azone) and derivatives thereof, and pyrothiodecane.

By fatty alcohol is meant a fatty alcohol containing from 6 to 20 carbon atoms. Fatty alcohols include, for example, lauryl alcohol, myristyl alcohol, oleyl alcohol, isostearyl alcohol, cetyl alcohol. Examples of polyhydric alcohols include propylene glycol.

Polyoxyethylene alkyl ethers include, for example, polyoxyethylene lauryl ether.

Examples of monoterpene compounds include geraniol, thymol, eugenol, terpineol, l-menthol, borneolol, d-limonene, isoeugenol, isoborneol, nerol and dl-camphor.

Oleyl alcohol, lauryl alcohol, isostearyl alcohol, lauric acid diethanolamide, glycerin monocaprylate, glycerin monocaprate, glycerin monooleate, sorbitan monolaurate, propylene glycol monolaurate, polyoxyethylene lauryl ether or pyrothiodecane preferable. Fatty acids are preferred, and oleic acid is particularly preferred.

The content of the percutaneous absorption enhancer is preferably 0 to 20% by mass, more preferably 0 to 10% by mass, based on the total mass of the adhesive layer.

Stabilizers include antioxidants (tocopherol derivatives, ascorbic acid derivatives, erythorbic acid derivatives, nordihydroguaiaretic acid, gallic acid derivatives, dibutylhydroxytoluene (BHT), butylhydroxyanisole, sodium pyrosulfite, sodium sulfite, 2 -mercaptobenzimidazole, etc.), UV absorbers (imidazole derivatives, benzotriazole derivatives, p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, cinnamic acid derivatives, benzophenone derivatives, coumaric acid derivatives, camphor derivatives, etc.) be able to. Two or more of these stabilizers may be used in combination.

The content of the stabilizer is preferably 0 to 5% by mass, more preferably 0 to 2% by mass, based on the total mass of the adhesive layer. By containing a stabilizer in the pressure-sensitive adhesive layer, the stability of fentanyl or a salt thereof can be further improved.

Fillers include metal oxides (zinc oxide, titanium oxide, etc.), metal salts (calcium carbonate, magnesium carbonate, zinc stearate, etc.), silicate compounds (kaolin, talc, bentonite, aerosil, hydrated silica, aluminum silicate, magnesium silicate, magnesium aluminometasilicate, etc.), metal hydroxides (aluminum hydroxide, etc.), and the like. Two or more of these fillers may be combined.

The content of the filler is preferably 0 to 10% by mass, more preferably 0 to 5% by mass, based on the total mass of the pressure-sensitive adhesive layer.

The adhesive layer may contain a solvent. Examples of solvents include methanol, ethanol, acetone, ethyl acetate, toluene, tetrahydrofuran, acetonitrile and the like. Two or more of these solvents may be combined.

The mass per unit area (1 m ² ) of the adhesive layer (plaster) may be 25 to 75 g/m ² , preferably 30 to 70 g/m ² , more preferably 35 to 60 g/m ² . It is more preferable to have

The support is not particularly limited as long as it is suitable for supporting the pressure-sensitive adhesive layer, and a stretchable or non-stretchable support can be used. Materials for the support include polyethylene (PE), polypropylene (PP), polybutadiene, ethylene-vinyl acetate copolymer, polyvinyl chloride, polyester, nylon, polyurethane, polyacrylonitrile (PAN) films, sheets, and laminates thereof. Materials such as bodies, porous bodies, foams, cloths and non-woven fabrics, and laminates thereof can be used. A preferred material for the support is polyethylene terephthalate (PET) or polyethylene. Specific examples of preferred supports include Scotchpak series (manufactured by 3M) such as Scotchpak (registered trademark) 9723 and 9732.

The support may be subjected to a sand matting treatment on the surface in contact with the pressure-sensitive adhesive layer. By applying a sand mat treatment to the support, the anchoring property is further improved. As a method of sand matting, a method well known to those skilled in the art can be used.

The patch according to this embodiment may include a release liner so as to cover the sticking surface of the pressure-sensitive adhesive layer. That is, when the patch has a release liner, the patch has a three-layer structure in which the pressure-sensitive adhesive layer is sandwiched between the backing and the release liner.

The patch according to the present embodiment is prepared by spreading a paste liquid obtained by mixing fentanyl or a salt thereof, an adhesive, and optionally other ingredients on a support, and laminating a release liner thereon. can be obtained by Alternatively, the base liquid may be spread on a release liner and the support may be laminated thereon.

The patch according to this embodiment is preferably stored in a pouch.

EXAMPLES The present invention will be described in more detail below using examples and comparative examples.

Test Example 1: Storage Stability Test 1
Tape preparations containing fentanyl citrate (Comparative Examples 1 and 2) were prepared according to the description in Table 1. Specifically, the adhesive liquid obtained by mixing each component is spread on the support so that the mass of the pressure-sensitive adhesive layer to be formed is 50 g/m ² , and the release liner is laminated thereon. By doing so, a tape agent was obtained. The tape of Comparative Example 1 has an application area of 5 cm ² and contains 1 mg of fentanyl citrate in the adhesive layer. On the other hand, the tape of Comparative Example 2 has an application area of 2.5 cm ² and contains 0.5 mg of fentanyl citrate in the adhesive layer.

The content of fentanyl citrate in each resulting tape was measured. After that, the tape was placed in an aluminum pouch and stored at 60° C. for 1 month, and then the content of fentanyl citrate contained in the adhesive layer was measured by high performance liquid chromatography. The content of fentanyl citrate after storage was calculated relative to the content of fentanyl citrate (initial value) when the tape was prepared.

Table 1 shows the results. In the tape preparation of Comparative Example 2, the content of fentanyl citrate after storage was lower than that of the tape preparation of Comparative Example 1.

Test Example 2: Storage stability test 2
Tape preparations containing fentanyl citrate (Examples 1 to 3) were prepared in the same manner as in Test Example 1 according to the description in Table 2. The tape preparations of Examples 1 to 3 are tape preparations having a lower concentration of fentanyl citrate in the adhesive layer and a larger application area than the tape preparation of Comparative Example 1. Storage stability of the tape preparations of Examples 1 to 3 was evaluated in the same manner as in Test Example 1.

Table 2 shows the results. In the tape preparations of Examples 1 to 3, the content of fentanyl citrate after storage at 60° C. for one month was 95% or more, and particularly in the tape preparations of Examples 2 and 3, it was about 96%.

Further, tapes (Examples 4 to 6) were prepared in the same manner as in Examples 1 to 3 except that only SIS was used as the adhesive instead of the combination of SIS and PIB. Further, tapes (Examples 7 to 9) were prepared in the same manner as in Examples 1 to 3 except that only PIB was used as the adhesive instead of the combination of SIS and PIB. A storage stability test was performed using the tape preparations of Examples 4-9, and the results were similar to those of Examples 1-3.

Test Example 3: Storage stability test 3
According to the description in Table 3, tapes (Examples 10 to 14) having the same composition as that of Example 2 but different shapes of application surfaces were prepared. The tape agents of Examples 2 and 10 to 14 have the same sticking area due to the difference in shape, but different lengths of the outer peripheries. Storage stability of the tape preparations of Examples 10 to 14 was evaluated in the same manner as in Test Example 1.

Table 3 shows the results. The shape of the application surface of Examples 11-14 is a rectangle having the aspect ratios listed in Table 3. There was a tendency for the content of fentanyl citrate to decrease as the perimeter of the application surface increased. When comparing tapes having the same application area, the surface area of the pressure-sensitive adhesive layer depends on the perimeter length of the application surface. Therefore, the tape agents of Examples 2 and 10 to 12, in which the surface area of the pressure-sensitive adhesive layer was smaller, exhibited higher storage stability of fentanyl citrate than the tape agents of Examples 13 and 14.

Claims (4)

A method for improving the storage stability of fentanyl or a salt thereof in a patch comprising an adhesive layer on a support, comprising:
The pressure-sensitive adhesive layer contains fentanyl or a salt thereof and at least one pressure-sensitive adhesive selected from styrene-isoprene-styrene copolymers and polyisobutylene ,
The content of fentanyl or a salt thereof in the pressure-sensitive adhesive layer is 0.1 to 0.8 mg when converted to fentanyl citrate, and 0 when converted to fentanyl citrate per 1 cm ² of the application area. adjusting to be between .01 and 0.18 mg;
adjusting the size of the patch so that the patch area is 3-8 cm ² and the perimeter length of the patch surface is 7.93-10.08 cm . The method according to claim 1, wherein said patch is a tape. The method according to claim 1 or 2 , wherein the concentration of said fentanyl or its salt is 1-3.5% based on the weight of said adhesive layer. The method according to any one of claims 1 to 3 , wherein the adhesive layer further contains a tackifying resin.