JP6658201B2 - Patch - Google Patents

Description

  The present invention relates to a patch for transdermally administering a drug.

  Various developments have been made on patches for transdermally administering drugs. Patches that are mainly put into practical use are those that transfer the drug from the plaster into the skin by utilizing the concentration difference between the drug concentration in the plaster pasted on the skin and the drug concentration in the skin. is there.

  The patch application area should be small as long as the desired amount of drug is absorbed into the systemic circulating bloodstream, so it is better to mix the drug in the plaster at a high concentration to increase the percutaneous absorption per unit area. Designs have been attempted.

  A high drug transdermal absorption rate can be expected by compounding the drug in the plaster layer at a high concentration and increasing the difference between the drug concentration dissolved in the plaster and the drug concentration in the skin. If the drug is precipitated in the body layer, the drug is released from the plaster layer and at the same time the precipitated drug dissolves in the plaster layer. It can be kept high and can be expected to maintain a high drug transdermal absorption rate.

  However, when the drug is mixed in the plaster layer at a high concentration, the elasticity and cohesiveness of the pressure-sensitive adhesive constituting the plaster layer significantly change, and not only the desired tackiness cannot be obtained, but also the adhesive patch During storage, there may be a problem such as cold flow of the plaster layer, and various methods have been provided to solve this problem.

  Patent Document 1 discloses a method of crosslinking an acrylic polymer using a metal alcoholate, a metal chelate compound, and / or an isocyanate compound in order to improve the cohesive strength of the acrylic pressure-sensitive adhesive.

  Patent Document 2 discloses a patch containing an adhesive base, a terpene, a sebacic ester, an alkyl glyceryl ether, and a nonsteroidal analgesic and anti-inflammatory drug.

  Patent Document 3 discloses that a plaster layer is provided on one side of a support, and that the adhesive layer contains fentanyl as an active ingredient and an adhesive base, and that the adhesive base contains styrene as a rubber component. -Contains an isoprene-styrene block copolymer and polyisoprene, and a terpene resin as a tackifier, and the content of the styrene-isoprene-styrene block copolymer is 0.2 times to 10 times the content of polyisoprene. An external patch having a mass ratio of twice as large has been proposed.

  Patent Document 4 discloses a skin patch in which a pressure-sensitive adhesive composition layer is formed on a support, wherein the pressure-sensitive adhesive composition layer is obtained by mixing at least two or more types of polymer materials, and at least one of the two or more polymer materials is mixed. A transdermal absorption preparation is disclosed, which is a polyether-based polymer material containing a siloxane bond, wherein at least one of the pressure-sensitive adhesive composition layers contains a physiologically active substance.

JP-A-3-220120 JP 2008-013494 A JP 2008-273865 A JP 2008-214312 A

  However, in Patent Document 1, when a cross-linking agent is used, the drug may be decomposed during storage by the cross-linking agent, and when the drug is blended at a high concentration, the cross-linking reaction of the pressure-sensitive adhesive by the cross-linking agent becomes insufficient, and The cohesive force required for the agent cannot be imparted, and there is a problem that a cold flow of the plaster layer occurs.

  When the non-steroidal analgesic anti-inflammatory agent is contained in the patch of Patent Document 2 at a high concentration of 10% or more, the adhesiveness of the plaster layer is reduced.

  In the external patch of Patent Document 3, when fentanyl is used at a high concentration of 6% by mass or more, there is a problem that the adhesiveness of the plaster layer is reduced.

  In the percutaneous absorption preparation of Patent Document 4, there is no disclosure about containing a drug in a plaster layer at a high concentration. Further, there is a problem that the drug reacts when the pressure-sensitive adhesive composition layer is crosslinked and the content of the drug decreases, and the content of the drug also decreases during storage.

  The present invention provides a patch which contains a drug in a plaster layer at a high concentration, has a plaster layer with excellent adhesiveness and cold flow resistance, and has excellent storage stability of the drug. provide.

The patch of the present invention comprises a support,
An acrylic pressure-sensitive adhesive laminated and integrated on one surface of the support and having a content of a drug and a crosslinking agent of 0.1% by mass or less, and a plaster layer containing a resin having a softening point of 80 ° C or more. It is characterized by including.

  The patch of the present invention can stably contain a drug at a high concentration in the plaster layer, and the plaster layer has excellent adhesiveness and cold flow resistance.

  The patch of the present invention includes a support and a plaster layer laminated and integrated on one surface of the support.

[Plastic layer]
The plaster layer is composed of an acrylic pressure-sensitive adhesive having a drug and a cross-linking agent content of 0.1% by mass or less, and a resin having a softening point of 80 ° C or more (hereinafter, sometimes referred to as “resin (A)”). It contains.

(Drug)
The plaster layer contains a drug. The drug, as long as it has percutaneous absorbability, for example, lidocaine, indomethacin, diclofenac, capsaicin, clonidine, selegiline, rotigotine, donepezil, free bases such as rivastigmine, fentanyl, buprenorphine, and these free bases Salts and esters are exemplified.

  The content of the drug in the plaster layer is preferably 10 to 50 parts by mass, more preferably 15 to 40 parts by mass, and particularly preferably 20 to 35 parts by mass with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive. When the content of the drug is 10 parts by mass or more, the patch area of the patch can be reduced, the patch can be hardly peeled off from the skin, and the use period of the patch can be lengthened. In addition, it is possible to reduce the burden on the patient due to the replacement of the patch. When the content of the drug is 50 parts by mass or less, the adhesiveness and the cold flow resistance of the plaster layer are improved. In the present invention, the content of the acrylic pressure-sensitive adhesive refers to the amount of the acrylic pressure-sensitive adhesive including the crosslinking agent when the crosslinking agent is included.

(Acrylic adhesive)
The plaster layer contains an acrylic pressure-sensitive adhesive. This acrylic pressure-sensitive adhesive contains a copolymer containing (meth) acrylate as a main monomer component. The acrylic pressure-sensitive adhesive may be selected from those capable of stably compounding the drug and the resin (A). The main monomer component refers to a monomer component having the largest content among the monomer components constituting the copolymer. The above copolymers may be used alone or in combination of two or more. (Meth) acrylate refers to acrylate or methacrylate

  Examples of the (meth) acrylate include methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl (meth) acrylate, isobutyl (meth) acrylate, and hexyl. (Meth) acrylate, n-octyl (meth) acrylate, isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, tridecyl (meth) acrylate, hexadecyl (meth) acrylate , Cyclododecyl (meth) acrylate, cyclohexyl (meth) acrylate, hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate and the like.

  A copolymerizable monomer copolymerizable with (meth) acrylate may be included as a monomer component constituting the copolymer. Examples of such a copolymerizable monomer include (meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride, acrylamide, dimethylacrylamide, acrylonitrile, dimethylaminoethyl (meth) acrylate, and t- (meth) acrylate. -Butylaminoethyl, vinyl acetate, vinyl propionate, vinyl pyrrolidone and the like. In addition, (meth) acrylic acid means acrylic acid or methacrylic acid.

  If the plaster layer contains more drug, the adhesive of the acrylic pressure-sensitive adhesive decreases, and the cohesive force of the acrylic pressure-sensitive adhesive decreases, causing a cold flow in the plaster layer. The agent is usually cross-linked using a cross-linking agent.

  The present inventors have conducted intensive studies and found that the cross-linking agent remaining in the acrylic pressure-sensitive adhesive has caused another problem of lowering the storage stability of the drug. Is that the content of the crosslinking agent contained in the acrylic pressure-sensitive adhesive is 0.1% by mass or less.

  In the acrylic pressure-sensitive adhesive, the amount of the crosslinking agent contained in the acrylic pressure-sensitive adhesive is set to 0.1% by mass or less. By setting the content of the cross-linking agent contained in the acrylic pressure-sensitive adhesive to 0.1% by mass or less, it is possible to prevent the decomposition of the drug caused by reacting with the cross-linking agent during storage of the patch. In addition, the storage stability of the drug can be improved. The content of the crosslinking agent contained in the acrylic pressure-sensitive adhesive is preferably 0.05% by mass or less, more preferably 0.01% by mass or less, and particularly preferably 0% by mass (the crosslinking agent is not contained). Is particularly preferred).

  Examples of the cross-linking agent include cross-linking agents conventionally used for cross-linking of an acrylic pressure-sensitive adhesive constituting a patch, such as N- (hydroxymethyl) acrylamide, N- (iso-butoxymethylene) acrylamide and methyl. Acrylamide compounds such as acrylamide glycolate methyl ether; epoxy compounds such as glycidyl methacrylate; polyisocyanates such as dicyclohexylmethane 4,4'-diisocyanate, 2,4-diisocyanotoluene, trimethylhexamethylene diisocyanate and isophorone diisocyanate Compound, aluminum acetylacetonate, chromium acetylacetonate, iron acetylacetonate, cobalt acetylacetonate, nickel acetylacetonate, manganese acetylacetone DOO, titanium acetylacetonate, metal chelate compounds such as zinc acetylacetonate and zirconium acetylacetonate, tetraisopropyl titanate, tetra-n- butyl titanate, a metal alkoxide compounds such as tetraethyl titanate and tetra-isobutyl titanate, and the like.

  The acrylic pressure-sensitive adhesive may be crosslinked, but is preferably not crosslinked. The gel fraction of the acrylic pressure-sensitive adhesive is preferably 0.1% by mass or less, more preferably 0.05% by mass or less, and particularly preferably 0% by mass (particularly preferably not crosslinked).

The gel fraction of the acrylic pressure-sensitive adhesive refers to a value measured in the following manner. The acrylic adhesive was weighed W ₀ g, immersed in xylene at 120 ° C. for 24 hours, and the insoluble matter was filtered through a 200-mesh wire gauze. It was measured (W ₁ g) and calculated by the following equation.
Gel fraction (% by mass) = (W ₁ / W ₀ ) × 100

  The holding power of the acrylic pressure-sensitive adhesive is preferably 60 minutes or more, more preferably 65 minutes or more, and particularly preferably 80 minutes or more. When the holding power of the acrylic pressure-sensitive adhesive is 60 minutes or more, the drug can be held at a high concentration in the acrylic pressure-sensitive adhesive. The higher the holding power of the acrylic pressure-sensitive adhesive, the better, but it is preferably 5000 minutes or less, more preferably 4000 minutes or less, and particularly preferably 3000 minutes or less.

  In the present invention, the holding force refers to a value measured in the following manner. A 100 μm thick acrylic plaster layer is formed on a support made of a polyethylene terephthalate film having a length of 20 mm, a width of 30 mm and a thickness of 38 μm to prepare a test piece.

  A clean stainless steel plate having a length of 50 mm, a width of 125 mm, and a thickness of 2 mm is prepared. A test body is prepared by reciprocating the roller twice at a speed of 10 mm / sec. The test specimen is allowed to stand at 40 ° C. for 20 minutes.

  Thereafter, the test piece was fixed such that the stainless plate of the test piece was vertical and the end of the test piece protruding from the stainless plate was on the lower side. Next, a test is started in an atmosphere of 40 ° C. with a 50 g weight attached to the end of the test piece protruding from the stainless steel plate of the test object via a hook.

The time from the start of the test until the test piece is completely separated from the stainless steel plate and falls is measured, and this time is defined as the holding force. If the test piece completely separates from the stainless steel plate and does not fall even after 60 minutes from the start of the test, the displacement L (mm) of the test piece in the vertical direction should be changed at the time of 60 minutes after the start of the test. The value obtained based on the following formula is measured and used as the holding force.
Holding force (min) = 60 + (25−L) × 60 / L

  The method for polymerizing the acrylic pressure-sensitive adhesive may be a conventionally known method. For example, a method of polymerizing the above-mentioned monomer in the presence of a polymerization initiator may be mentioned. Specifically, a predetermined amount of a monomer, a polymerization initiator, a polymerization solvent, and the like are supplied to a reactor, and heated at a temperature of 60 to 80 ° C. for 4 to 48 hours to radically polymerize the monomer.

  As the polymerization initiator, for example, 2,2′-azobisisobutyronitrile (AIBN), 1,1′-azobis (cyclohexane-1-carbonitrile), 2,2′-azobis- (2,4 ′) -Dimethyl valeronitrile); and peroxide-based polymerization initiators such as benzoyl peroxide (BPO), lauroyl peroxide (LPO), and di-tert-butyl peroxide. Examples of the polymerization solvent include ethyl acetate and toluene. Further, the polymerization reaction is preferably performed in a nitrogen gas atmosphere.

(Resin whose softening point is 80 ° C or higher)
The plaster layer contains a resin (resin (A)) having a softening point of 80 ° C. or higher. Since the plaster layer contains the acrylic pressure-sensitive adhesive and the resin (A) in combination, the plaster layer has excellent adhesiveness even when the plaster layer contains a drug at a high concentration. have.

  Furthermore, since the resin (A) is contained in the plaster layer, the cold flow of the plaster layer can be suppressed. Therefore, the drug can be contained in the plaster layer at a high concentration without significantly reducing the degree of crosslinking of the plaster layer or without crosslinking the plaster layer.

  And since the degree of crosslinking of the plaster layer is extremely low or there is no need to crosslink the plaster layer, the amount of the cross-linking agent used is extremely low or there is no need to use a crosslinking agent, and the drug is used in the production process of the plaster layer. It is possible to suppress the situation that the drug is decomposed by the cross-linking agent during the decomposition or storage of the patch, the drug is contained in the plaster layer at a high concentration, and the drug is contained in the plaster layer for a long time. It can be stably held throughout.

  The resin (A) is not particularly limited as long as it has miscibility with the acrylic resin. Examples of the resin (A) include alicyclic saturated hydrocarbon resins (for example, “Alcon” manufactured by Arakawa Chemical Industries, Ltd.), Terpene resins (eg, “YS resin” manufactured by Yashara Chemical Co., Ltd.), terpene phenol resins (eg, “YS Polystar” manufactured by Yashara Chemical Co., Ltd.), hydrogenated aromatic modified terpene resins (eg, “Clearon” manufactured by Yashara Chemical Co., Ltd.), Examples include aliphatic hydrocarbons (eg, “Escorez” manufactured by ExxonMobil), aromatic petroleum resins (eg, “Nisseki Neopolymer” manufactured by JX Nippon Oil & Energy), and terpene resins and terpene phenol resins. , Hydrogenated aromatic modified terpene resins and aromatic petroleum resins are preferable, and terpene resins and aromatic petroleum resins are more preferable. Ku, aromatic petroleum resins are particularly preferable. The resin (A) may be used alone or in combination of two or more.

  The softening point of the resin (A) is 80 ° C. or higher, since the cohesive force of the plaster layer can be improved to improve the cold flow resistance of the plaster layer and the holding power of the plaster layer. The temperature is preferably 118 ° C. or higher, more preferably 125 ° C. or higher, and particularly preferably 130 ° C. or higher. The softening point of the resin (A) is preferably 250 ° C. or lower, more preferably 200 ° C. or lower, since the tack of the plaster layer can be improved and the patch can be easily and stably adhered to the skin. 170 ° C. or lower is particularly preferred. The softening point of the resin (A) refers to a temperature measured in accordance with JIS K6863: 1994.

  The weight average molecular weight of the resin (A) is preferably from 400 to 10,000, more preferably from 450 to 7000, and particularly preferably from 500 to 4000. When the weight average molecular weight of the resin (A) is 400 or more, the patch can be stably stuck on the skin without accidental peeling during use. When the weight average molecular weight of the resin (A) is 10,000 or less, the resin (A) can be mixed well with the acrylic pressure-sensitive adhesive, thereby improving the adhesiveness and cold flow resistance of the plaster layer, and having a high level in the plaster layer. Drug can be included in the concentration.

  The content of the resin (A) in the plaster layer is preferably from 20 to 80 parts by mass, more preferably from 25 to 75 parts by mass, still more preferably from 30 to 70 parts by mass, based on 100 parts by mass of the acrylic resin. Particularly preferred is from 70 to 70 parts by mass. When the content of the resin (A) is at least 20 parts by mass, the shear viscosity inside the plaster layer can be improved and the adhesiveness of the plaster layer can be improved, which is preferable. When the content of the resin (A) is 80 parts by mass or less, the cold flow resistance of the plaster layer can be improved while maintaining the high adhesiveness of the plaster layer.

(Additive)
The plaster layer may contain additives such as a plasticizer and a filler as long as the physical properties are not impaired.

  The plasticizer is added for the purpose of improving the adhesive properties of the plaster layer. The plasticizer is not particularly limited as long as it is compatible with the acrylic pressure-sensitive adhesive.For example, esters such as isopropyl myristate, decyl oleate, and isopropyl adipate, myristyl alcohol, cetanol, octyl dodecanol, Examples include monohydric alcohols such as isostearyl alcohol and stearyl alcohol, dihydric alcohols such as octanediol, acids such as oleic acid and stearic acid, and liquid paraffin. Liquid paraffin, isopropyl myristate, and octyldodecanol are preferred. .

  The content of the plasticizer in the plaster layer is preferably 5 to 50 parts by mass, more preferably 5 to 45 parts by mass, still more preferably 5 to 15 parts by mass, based on 100 parts by mass of the acrylic pressure-sensitive adhesive. 15 parts by weight are particularly preferred. When the content of the plasticizer is 5 parts by mass or more, a necessary tack can be imparted to the plaster layer when the patch is applied to the skin, which is preferable. When the content of the plasticizer is 50 parts by mass or less, the patch can be stably stuck without causing a shift on the skin, and when the patch is peeled from the skin. This is preferable because a situation in which a part of the plaster layer remains on the surface can be suppressed.

  The filler is added for the purpose of improving the uniformity of the plaster layer. Examples of the filler include light anhydrous silicic acid and crosslinked polyvinylpyrrolidone.

  The thickness of the plaster layer is preferably 30 to 300 μm, more preferably 40 to 250 μm, and particularly preferably 50 to 200 μm. When the thickness of the plaster layer is 30 μm or more, a necessary amount of drug can be contained in the plaster layer to obtain a desired drug effect. When the thickness of the plaster layer is 300 μm or less, since strong drying conditions are not required at the time of production to reduce the residual solvent in the plaster layer, it is possible to suppress the volatilization or decomposition of the drug in the plaster layer. it can.

  The holding power of the plaster layer is preferably 55 minutes or less, more preferably 5 to 50 minutes, further preferably 10 to 48 minutes, and particularly preferably 10 to 45 minutes. If the holding power of the plaster layer is 55 minutes or less, the plaster layer smoothly absorbs the external force even if an external force is applied to the patch stuck on the skin in the peeling direction, and the patch is applied to the skin. Can be prevented from being accidentally peeled off from the substrate. When the holding power of the plaster layer is 5 minutes or more, the cold flow resistance of the plaster layer is improved.

  The holding power of the plaster layer was obtained by measuring the holding force of the acrylic pressure-sensitive adhesive in the above-described method of measuring the holding power of the acrylic pressure-sensitive adhesive. The test piece can be measured in the same manner except that this test piece is used.

(Support)
In the patch of the present invention, the above-mentioned plaster layer is laminated and integrated on one surface of the support. The support is required to have a strength to prevent loss of the drug in the plaster layer and to give the patch a self-holding property. Examples of such a support include a resin film, a nonwoven fabric, a woven fabric, a knitted fabric, and an aluminum sheet.

  As a resin constituting the resin film, for example, cellulose acetate, rayon, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, Examples include polypropylene and polyvinylidene chloride. Of these, polyethylene terephthalate is particularly preferred because even a volatile drug can prevent the loss of the drug from the plaster layer.

  As a material constituting the nonwoven fabric, for example, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ethylene-methyl (meth) acrylate copolymer, nylon, polyester, vinylon, styrene-isoprene-styrene block copolymer, Styrene-ethylene / butylene-styrene block copolymer, rayon, cotton and the like are mentioned, and polyester is preferable. These materials may be used alone or in combination of two or more.

  The support may be a single layer or a laminated sheet in which a plurality of layers are integrally laminated. Examples of the laminated sheet include a laminated sheet in which a polyethylene terephthalate sheet and a nonwoven fabric or a flexible resin sheet are laminated and integrated.

  The thickness of the support is not particularly limited, but is preferably 2 to 200 μm, more preferably 2 to 100 μm.

[Release liner]
In the patch of the present invention, a release liner may be laminated and integrated on one surface of the plaster layer so as to be peelable. The release liner is used to prevent the loss of the drug in the plaster layer and to protect the plaster layer.

  Examples of the release liner include paper and a resin film. Examples of the resin constituting the resin film include polyethylene terephthalate, polyethylene, polypropylene, polyvinyl chloride, polyvinylidene chloride and the like. The surface of the release liner facing the plaster layer is preferably subjected to a release treatment.

(Production method of patch)
The method for producing the patch of the present invention includes, for example, (1) applying a plaster layer solution containing an acrylic pressure-sensitive adhesive, a resin (A), a drug and a solvent onto one surface of a support, followed by drying. Then, the paste layer is laminated and integrated on one surface of the support, and if necessary, the release liner is applied to the paste layer, so that the release-treated surface of the release liner faces the paste layer. A method of laminating, (2) applying the above-mentioned plaster layer solution on the release liner-treated surface of the release liner and drying it to form a plaster layer on the release liner; And a method of laminating and integrating a support.

  The plaster layer solution is obtained by uniformly stirring the acrylic pressure-sensitive adhesive, resin (A), drug and solvent. The solvent is not limited as long as it can dissolve the acrylic pressure-sensitive adhesive and the resin (A). For example, toluene, normal hexane, cyclohexane, normal heptane, and ethyl acetate are preferable.

  Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited thereto.

(Preparation of Acrylic Adhesive A)
A reaction solution consisting of a monomer containing 13 parts by weight of dodecyl methacrylate, 78 parts by weight of 2-ethylhexyl methacrylate and 9 parts by weight of 2-ethylhexyl acrylate, and 50 parts by weight of ethyl acetate is supplied to a separable flask. C. and a nitrogen atmosphere. Then, the monomer was copolymerized while adding a polymerization initiator solution obtained by dissolving 1 part by weight of lauroyl peroxide in 50 parts by weight of cyclohexane to the reaction solution over 24 hours. After the polymerization was completed, ethyl acetate was further added to the reaction solution. Was added to obtain an acrylic pressure-sensitive adhesive solution A having a content of the acrylic pressure-sensitive adhesive A of 35% by mass.

(Preparation of acrylic pressure-sensitive adhesive B)
A reaction solution comprising 100 parts by weight of ethyl acrylate, 80 parts by weight of n-octyl acrylate and 20 parts by weight of 1-vinyl-2-pyrrolidone, and 200 parts by weight of ethyl acetate was supplied to a separable flask. The inside of the bull flask was set to a nitrogen atmosphere at 80 ° C. Then, the monomer was polymerized while adding a polymerization initiator solution obtained by dissolving 1 part by weight of lauroyl peroxide in 50 parts by weight of cyclohexane to the reaction solution over 27 hours. After the polymerization was completed, ethyl acetate was further added to the reaction solution. In addition, an acrylic pressure-sensitive adhesive solution B having an acrylic pressure-sensitive adhesive B content of 32% by mass was obtained.

[Resin whose softening point is 80 ° C or higher]
・ Terpene resin (trade name “YS Resin PX1150N” manufactured by Yashara Chemical Co., Ltd.)
(Point: 115 ° C., weight average molecular weight: 3400)
・ Terpene phenol resin (trade name “YS Polystar T115” manufactured by Yashara Chemical Co., Ltd.)
(Softening point: 115 ° C, weight average molecular weight: 500 to 1050)
・ Hydrogenated aromatic modified terpene resin (trade name “Clearon M115” manufactured by Yasuhara Chemical Co., Ltd.)
(Softening point: 115 ° C, weight average molecular weight: 600 to 700)
・ Aromatic petroleum resin (trade name “Nisseki Neopolymer 120” manufactured by JX Nippon Oil & Energy)
(Softening point: 120 ° C, weight average molecular weight: 1500)
・ Aromatic petroleum resin (trade name “Nisseki Neopolymer 170S” manufactured by JX Nippon Oil & Energy Corporation, softening point: 160 ° C, weight average molecular weight: 3000)

(Examples 1 to 13, Comparative Examples 1 to 3)
Drug, acrylic adhesive A (crosslinking agent: 0% by mass, gel fraction: 0% by mass), acrylic resin B (crosslinking agent: 0% by mass, gel fraction: 0% by mass), acrylic adhesive C (Henkel's trade name "Duro-tack", content of crosslinking agent: more than 0.1% by mass, gel fraction: 70% by mass), resin having a softening point of 80 ° C or higher, liquid paraffin, myristic acid Isopropyl and octyl dodecanol were blended in predetermined amounts shown in Table 1, and ethyl acetate was added so that the solid concentration became 25% by weight, and then mixed until uniform to prepare a plaster layer solution. did.

  Next, a 38 μm-thick polyethylene terephthalate film having been subjected to a silicone release treatment was prepared as a release liner, and the above-mentioned plaster layer solutions were applied to the silicone release-treated surface of the polyethylene terephthalate film. For 20 minutes to produce a laminate in which a plaster layer having a thickness shown in Table 1 was formed on the silicone release treated surface of the polyethylene terephthalate film.

  Then, a polyethylene terephthalate film having a thickness of 38 μm is prepared as a support, and one surface of the support is superimposed on the plaster layer of the laminate so that the plaster layer of the laminate faces the support. The patch was manufactured by transferring and laminating and integrating.

  With respect to the obtained patch, the adhesive strength, storage stability (cold flow) and storage stability (drug concentration) were measured in the following manner, and the results are shown in Table 1.

  With respect to the obtained patch, the holding power of the plaster layer was measured in the manner described above, and the results are shown in Table 1. The holding power of the acrylic pressure-sensitive adhesive constituting the plaster layer was measured as described above, and the results are shown in Table 1.

〔Adhesive force〕
Three test pieces (width 25 mm × length 15 mm) were cut out from the patch. For each test piece, the peeling adhesive strength (g / 25 mm) was measured according to the 180 ° peeling test specified in JIS Z0237 (2009), and the addition of the peeling adhesive strength of three test pieces was performed. The average value was defined as the adhesive strength of the patch.

[Storage stability (cold flow)]
An arbitrary portion of the patch was cut to obtain one test piece (3 cm ^{2 in} area). The test piece was sealed in a transparent, patch-like packaging material having a square shape of 5 cm on a side and stored at 60 ° C. for 1 week, and then the cold flow was visually evaluated based on the following criteria.
-: There was no protrusion of the plaster layer.
+/-: Slight protrusion was found on a part of the plaster layer.
+: The plaster layer protruded all around the test piece.
++: The plaster layer of 0.5 mm or more protruded.

[Storage stability (drug concentration)]
By cutting an arbitrary part of the patch, six test pieces (area 3 cm ² ) were obtained. The test piece was sealed in a light-shielding patch packaging material having a flat square shape with a side of 5 cm, and three pieces were stored at 4 ° C., and the remaining three pieces were stored at 60 ° C. for 2 weeks. After storage, the weight Wt of each test piece was measured, the release liner was removed, and then the drug in the plaster layer was extracted using an extract (ethyl acetate: methanol = 3: 2), and then HPLC was used. The drug weight Wr in the patch was quantified. After the support was washed with ethyl acetate or toluene and dried, the weight Wp of the release liner and the support together was measured. The drug concentration in the plaster layer was calculated using the following formula (1).
Drug concentration (%) = 100 × Wr / (Wt−Wp) Formula (1)

The arithmetic mean of the drug concentration in the plaster layer of the three test pieces stored at 4 ° C. is C ₄ , the arithmetic mean value of the drug concentration in the plaster layer of the three test pieces stored at 60 ° C. Was _defined as C _60, and the residual ratio of the drug was calculated using the following equation (2).
Drug residual rate (%) = 100 × C ₆₀ / C ₄ (2)

  The patch of the present invention can stably contain a drug at a high concentration in the plaster layer, and the plaster layer has excellent adhesiveness and cold flow resistance.

Claims (5)

A support,
10 to 50 parts by mass of a drug laminated and integrated on one surface of the support, 100 parts by mass of an acrylic pressure-sensitive adhesive having a crosslinking agent content of 0.1% by mass or less, and a softening point of 110 ° C or more . An adhesive patch comprising a plaster layer containing 20 to 80 parts by mass of a resin (excluding a case where a rubber-based polymer is contained) . The patch according to claim 1, wherein the resin having a softening point of 110 ° C or higher has a weight average molecular weight of 400 to 10,000. The patch according to claim 1 or 2, wherein the plaster layer contains 5 to 50 parts by mass of a plasticizer with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive.   The patch according to any one of claims 1 to 3, wherein the holding power of the acrylic pressure-sensitive adhesive is 60 minutes or more. The patch according to any one of claims 1 to 4 , wherein a holding force of the plaster layer is 55 minutes or less.