JP2017178799A - Patches - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide patches which can allow a drug to be contained in a plaster layer at high concentration stably and which simultaneously have excellent adhesiveness and cold flow-resistance of a plaster layer.SOLUTION: Since a patch of the present invention is characterized by containing a support, an acrylic pressure-sensitive adhesive laminated and integrated on one side of the support and having a content of a drug and a crosslinking agent of 0.1 mass% or less, and a plaster layer containing a resin having a softening point of 80°C or more, it allows a drug to be contained in a plaster layer at high concentration stably and simultaneously has excellent adhesiveness and cold flow-resistance of a plaster layer.SELECTED DRAWING: None

Description

  The present invention relates to a patch for transdermal administration of a drug.

  Various developments have been made on patches for transdermal administration of drugs. Patches that have been put to practical use mainly transfer the drug from the plaster to the skin using the concentration difference between the drug concentration in the paste applied on the skin and the drug concentration in the skin. is there.

  The patch area should be small as long as the desired amount of drug can be absorbed into the systemic bloodstream, and it should be small. In order to increase the amount of percutaneous absorption per unit area, the drug is formulated in a high concentration in the plaster. Design has been attempted.

  A high drug transdermal absorption rate can be expected by blending the drug at a high concentration in the plaster layer and increasing the difference between the drug concentration dissolved in the plaster and the drug concentration in the skin. When the drug is deposited in the body layer, the drug is released from the paste layer and the deposited drug dissolves in the paste layer. A high drug transdermal absorption rate can also be expected.

  However, when a high concentration of the drug is blended in the plaster layer, the elasticity and cohesiveness of the adhesive constituting the plaster layer changes greatly, and the desired adhesiveness cannot be obtained. Problems such as cold flow of the paste layer may occur during storage, and various methods are 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 acid ester, an alkyl glyceryl ether, and a non-steroidal analgesic / anti-inflammatory agent.

  In Patent Document 3, a plaster layer is provided on one side of a support, and the adhesive layer contains fentanyl and an adhesive base as active ingredients. In the adhesive base, styrene is used as a rubber component in the adhesive base. -Isoprene-styrene block copolymer and polyisoprene and a terpene resin as a tackifier, and the content of styrene-isoprene-styrene block copolymer is 0.2 mass times to 10 times the content of polyisoprene. A patch for external use having a mass ratio has been proposed.

  In Patent Document 4, in a skin patch in which an adhesive composition layer is formed on a support, the adhesive composition layer is a mixture of at least two polymer materials, and at least one of them is Disclosed is a percutaneous absorption preparation which is a polyether polymer material containing a siloxane bond, wherein at least one of the pressure-sensitive adhesive composition layers contains a physiologically active substance.

Japanese Patent Laid-Open No. 3-220120 JP 2008-013494 A JP 2008-273865 A JP 2008-214312 A

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

  In the patch of Patent Document 2, when the non-steroidal analgesic / anti-inflammatory agent is contained at a high concentration of 10% or more, there is a problem that the adhesiveness of the paste layer is lowered.

  In the external patch of Patent Document 3, when the concentration of fentanyl is 6% by mass or more, there is a problem that the adhesiveness of the paste layer is lowered.

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

  The present invention provides a patch having excellent adhesiveness and cold flow resistance, and having excellent drug storage stability while containing a high concentration of the drug in the plaster layer. provide.

The patch of the present invention comprises a support,
A plaster layer containing an acrylic pressure-sensitive adhesive layered and integrated on one surface of the support and having a drug and a crosslinking agent content of 0.1% by mass or less, and a resin having a softening point of 80 ° C. or higher; 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.

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

(Drug)
The plaster layer contains a drug. Any drug may be used as long as it has a transdermal absorbability. Examples include salts and ester forms.

  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 application area can be reduced, the patch can be made difficult to peel off from the skin, and the period of use of the patch can be prolonged. Therefore, the burden on the patient associated with the patch replacement can be reduced. When the content of the drug is 50 parts by mass or less, the adhesiveness and cold flow resistance of the plaster layer are improved. In the present invention, the content of the acrylic pressure-sensitive adhesive means the amount of the acrylic pressure-sensitive adhesive including the cross-linking agent when a cross-linking 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 adhesive may be selected from those that can stably blend the drug and the resin (A). The main monomer component means the monomer component having the highest content among the monomer components constituting the copolymer. In addition, the said copolymer may be used independently or 2 or more types may be used together. (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.

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

  When a larger amount of drug is contained in the plaster layer, the tackiness of the acrylic pressure-sensitive adhesive decreases, and the cohesive force of the acrylic pressure-sensitive adhesive decreases to cause cold flow in the plaster layer. The agent is usually crosslinked using a crosslinking agent.

  As a result of intensive studies by the present inventors, it has been found that the crosslinking agent remaining in the acrylic pressure-sensitive adhesive causes another problem that the storage stability of the drug is lowered. The content of the crosslinking agent contained in the acrylic pressure-sensitive adhesive is 0.1% by mass or less.

  In the acrylic adhesive, the amount of the crosslinking agent contained in the acrylic adhesive is 0.1% by mass or less. By making the content of the crosslinking agent contained in the acrylic pressure-sensitive adhesive 0.1% by mass or less, it is possible to prevent the decomposition of the drug due to the reaction with the crosslinking agent during storage of the patch. The storage stability of the drug can be improved. The content of the crosslinking agent contained in the acrylic adhesive is preferably 0.05% by mass or less, more preferably 0.01% by mass or less, and particularly preferably 0% by mass (no crosslinking agent is contained). Is particularly preferred).

  Examples of the cross-linking agent include cross-linking agents conventionally used for cross-linking the acrylic pressure-sensitive adhesive constituting the 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, Cronium acetylacetonate, Iron acetylacetonate, Cobalt acetylacetonate, Nickel acetylacetonate, Manganese acetylacetonate 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 cross-linked, but is preferably not cross-linked. 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 is a value measured in the following manner. Weigh the acrylic pressure-sensitive adhesive W ₀ g, soak it in xylene at 120 ° C. for 24 hours, filter the insoluble matter with a 200-mesh wire mesh, vacuum dry the residue on the wire mesh, and dry the weight of the residue. Measured (W ₁ g) and calculated by the following formula.
Gel fraction (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. However, 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 test piece is prepared by forming an acrylic paste layer having a thickness of 100 μm 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.

  Prepare a clean stainless steel plate with a length of 50 mm, a width of 125 mm, and a thickness of 2 mm, and paste the test piece on the stainless steel plate so that the end 5 mm in the horizontal direction protrudes from the stainless steel plate, and 2 kg of rubber on the test piece. A test body is produced 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 body was fixed so that the stainless steel plate of the test body was vertical and the end of the test piece protruding from the stainless steel plate was on the lower side. Next, a 50 g weight is attached to the end of the test piece protruding from the stainless steel plate of the test body via a hook, and the test is started in an atmosphere of 40 ° C.

The time from the start of the test until the test piece completely peels off from the stainless steel plate and falls is measured, and this time is taken as the holding force. If the test piece does not completely peel off from the stainless steel plate after 60 minutes from the start of the test and does not drop, the displacement L (mm) of the test piece in the vertical direction is set at the time when 60 minutes have passed since the start of the test. Measure and use the value obtained based on the following formula as the holding force.
Holding power (min) = 60 + (25−L) × 60 / L

  What is necessary is just to perform by the conventionally well-known method as a polymerization method of an acrylic adhesive. For example, a method of polymerizing the above-described monomer in the presence of a polymerization initiator can be mentioned. Specifically, a predetermined amount of a monomer, a polymerization initiator, a polymerization solvent, and the like are supplied to the reactor and heated at a temperature of 60 to 80 ° C. for 4 to 48 hours to radically polymerize the monomer.

  Examples of the polymerization initiator include 2,2′-azobisisobutyronitrile (AIBN), 1,1′-azobis (cyclohexane-1-carbonitrile), 2,2′-azobis- (2,4 ′). -Azobis-based polymerization initiators such as dimethylvaleronitrile); 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. Furthermore, the polymerization reaction is preferably performed in a nitrogen gas atmosphere.

(Resin having a softening point of 80 ° C or higher)
The plaster layer contains a resin [resin (A)] having a softening point of 80 ° C. or higher. By including the acrylic adhesive and the resin (A) in combination in the paste layer, the paste layer has excellent adhesiveness even when the paste layer contains a drug at a high concentration. have.

  Furthermore, the cold flow of the paste layer can be suppressed by containing the resin (A) in the paste layer. Therefore, a high concentration of the drug can be contained in the plaster layer without extremely reducing the degree of crosslinking of the plaster layer or without crosslinking the plaster layer.

  And since the degree of cross-linking of the plaster layer is extremely low or it is not necessary to cross-link the plaster layer, the amount of the cross-linking agent used is extremely low or it is not necessary to use a cross-linking agent. It is possible to prevent the drug from being decomposed or decomposed by the crosslinking agent during storage of the patch, and to contain the drug in a high concentration in the plaster layer and to keep the drug in the plaster layer for a long period of time. It can be stably held over.

  The resin (A) is not particularly limited as long as it has miscibility with the acrylic resin. For example, an alicyclic saturated hydrocarbon resin (for example, “Arcon” manufactured by Arakawa Chemical Industries), Terpene resin (for example, “YS Resin” manufactured by Yasuhara Chemical Co., Ltd.), terpene phenol resin (for example, “YS Polystar” manufactured by Yasuhara Chemical Co., Ltd.), hydrogenated aromatic modified terpene resin (for example, “Clearon” manufactured by Yasuhara Chemical Co., Ltd.), Aliphatic hydrocarbons (for example, “Escorez” manufactured by ExxonMobil), aromatic petroleum resins (for example, “Nisseki Neopolymer” manufactured by JX Nippon Mining & Energy Corporation), terpene resins, terpene phenol resins Hydrogenated aromatic modified terpene resins and aromatic petroleum resins are preferred, terpene resins and aromatic petroleum resins are more preferred. Ku, aromatic petroleum resins are particularly preferable. In addition, resin (A) may be used independently or 2 or more types may be used together.

  The softening point of the resin (A) is 80 ° C. or higher because it can improve the cold flow resistance of the paste layer and the holding power of the paste layer by improving the cohesive strength of the paste layer. The above is preferable, 118 ° C. or higher is more preferable, 125 ° C. or higher is further preferable, and 130 ° C. or higher is particularly preferable. The softening point of the resin (A) improves the tackiness of the plaster layer and allows the patch to be easily and stably attached to the skin. Therefore, the softening point is preferably 250 ° C or lower, more preferably 200 ° C or lower, 170 degrees C or less is especially preferable. In addition, the softening point of resin (A) means the temperature measured based on JISK6863: 1994.

  400-10000 are preferable, as for the weight average molecular weight of resin (A), 450-7000 are more preferable, and 500-4000 are especially preferable. When the weight average molecular weight of the resin (A) is 400 or more, the patch can be stably stuck on the skin without being accidentally peeled off during use. When the weight average molecular weight of the resin (A) is 10,000 or less, the resin (A) can be well mixed with the acrylic pressure-sensitive adhesive, and can improve the adhesiveness and cold flow resistance of the plaster layer. The drug can be included in the concentration.

  The content of the resin (A) in the plaster layer is preferably 20 to 80 parts by mass, more preferably 25 to 75 parts by mass, and still more preferably 30 to 70 parts by mass with respect to 100 parts by mass of the acrylic resin. -70 mass parts is especially preferable. When the content of the resin (A) is 20 parts by mass or more, it is preferable because the shear viscosity inside the paste layer can be improved and the adhesiveness of the paste layer can be improved. When the content of the resin (A) is 80 parts by mass or less, the cold flow resistance of the paste layer can be improved while maintaining high adhesiveness of the paste layer.

(Additive)
The plaster layer may contain additives such as plasticizers and fillers as long as the physical properties thereof 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, isopropyl adipate, myristyl alcohol, cetanol, octyldodecanol, Examples thereof 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, further preferably 5 to 15 parts by mass, with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive. 15 parts by mass is particularly preferred. When the content of the plasticizer is 5 parts by mass or more, a tack necessary for sticking the patch to the skin can be imparted to the plaster layer, which is preferable. When the content of the plasticizer is 50 parts by mass or less, it is possible to maintain a state in which the patch is stably adhered without causing displacement on the skin, and when the patch is peeled from the skin It is possible to suppress a situation in which a part of the plaster layer remains.

  The filler is added for the purpose of improving the uniformity of the paste layer. Examples of the filler include light silicic anhydride and cross-linked polyvinyl pyrrolidone.

  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 in order to obtain a desired medicinal effect. If the thickness of the plaster layer is 300 μm or less, it does not require strong drying conditions at the time of manufacture in order to reduce the residual solvent in the plaster layer, thereby suppressing 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, still more preferably 10 to 48 minutes, and particularly preferably 10 to 45 minutes. When the retention strength of the plaster layer is 55 minutes or less, even if an external force is applied to the patch applied on the skin in the peeling direction, the plaster layer absorbs the external force smoothly and the patch is applied on the skin. Can be prevented from being accidentally peeled off. When the holding power of the paste layer is 5 minutes or more, the cold flow resistance of the paste layer is improved.

  Note that the holding power of the plaster layer is the same as that of the above-described method for measuring the holding power of the acrylic pressure-sensitive adhesive on the support made of a polyethylene terephthalate film having a thickness of 100 μm instead of an acrylic plaster layer. The test piece can be prepared in the same manner except that this test piece is used.

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

  Examples of the resin constituting the resin film include cellulose acetate, rayon, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, Examples thereof include polypropylene and polyvinylidene chloride. Among them, polyethylene terephthalate is particularly preferable because it can prevent loss of the drug from the plaster layer even if it is a volatile drug.

  Examples of the material constituting the nonwoven fabric include polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ethylene- (meth) acrylate methyl copolymer, nylon, polyester, vinylon, styrene-isoprene-styrene block copolymer, Examples thereof include styrene-ethylene / butylene-styrene block copolymers, rayon, and cotton, and polyester is preferred. In addition, these materials may be used independently or 2 or more types may be used together.

  The support may be a single layer or a laminated sheet in which a plurality of layers are laminated and integrated. 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.

  Although the thickness in particular of a support body is not restrict | limited, 2-200 micrometers is preferable and 2-100 micrometers is more preferable.

[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 peeled off. The release liner is used for preventing loss of the drug in the paste layer and protecting the paste 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, and polyvinylidene chloride. It is preferable that a release treatment is performed on the surface of the release liner facing the plaster layer.

(Manufacturing method of patch)
As a method for producing the patch of the present invention, for example, (1) a plaster layer solution containing an acrylic pressure-sensitive adhesive, a resin (A), a drug and a solvent is applied to one surface of a support and then dried. The plaster layer is laminated and integrated on one surface of the support, and if necessary, the release liner is applied to the plaster layer, and the surface of the release liner that has been subjected to the release treatment faces the plaster layer. (2) The plaster layer solution is coated on the release liner surface of the release liner and dried to form a paste layer on the release liner. And a method in which the support is laminated and integrated.

  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 specifically described with reference to examples, but the present invention is not limited thereto.

(Preparation of acrylic adhesive A)
A reaction solution comprising 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 was supplied to the separable flask. A nitrogen atmosphere was used. Then, the monomer is 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, and further ethyl acetate is added to the reaction solution after the polymerization is completed. Was added to obtain an acrylic adhesive solution A having an acrylic adhesive A content of 35% by mass.

(Preparation of acrylic adhesive B)
After supplying a reaction solution consisting of 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 to a separable flask, The inside of the bull flask was made into a nitrogen atmosphere at 80 ° C. Then, the monomer is polymerized while adding a polymerization initiator solution in which 1 part by weight of lauroyl peroxide is dissolved in 50 parts by weight of cyclohexane to the reaction liquid over 27 hours. After the polymerization is completed, ethyl acetate is further added to the reaction liquid. In addition, an acrylic adhesive solution B having an acrylic adhesive B content of 32% by mass was obtained.

[Resin having a softening point of 80 ° C. or higher]
-Terpene resin (trade name “YS Resin PX1150N” manufactured by Yasuhara Chemical Co., Ltd.)
Point: 115 ° C., weight average molecular weight: 3400)
・ Terpene phenol resin (trade name “YS Polystar T115” manufactured by Yasuhara 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 Corporation)
(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 1-13, Comparative Examples 1-3)
Drug, acrylic adhesive A (crosslinking agent: 0 mass%, gel fraction: 0 mass%), acrylic resin B (crosslinking agent: 0 mass%, gel fraction: 0 mass%), acrylic adhesive C (Product name “Duro-tack” manufactured by Henkel, content of crosslinking agent: more than 0.1% by mass, gel fraction: 70% by mass), resin having softening point of 80 ° C. or higher, liquid paraffin, myristic acid Isopropyl and octyldodecanol are blended in the prescribed amounts shown in Table 1, and ethyl acetate is added so that the solid content is 25% by weight. did.

  Next, a 38 μm thick polyethylene terephthalate film subjected to silicone release treatment was prepared as a release liner, and each plaster layer solution was applied to the silicone release treatment surface of the polyethylene terephthalate film at 80 ° C. Was dried for 20 minutes to produce a laminate in which the plaster layer having the thickness shown in Table 1 was formed on the silicone release treatment surface of the polyethylene terephthalate film.

  Then, a polyethylene terephthalate film having a thickness of 38 μm is prepared as a support, and is laminated so that one surface of the support and the paste layer of the laminate are opposed to each other, and the paste layer of the laminate is used as a support. A patch was produced by transferring and laminating and integrating.

  The adhesive patch obtained was measured for adhesive strength, storage stability (cold flow) and storage stability (drug concentration) in the following manner, and the results are shown in Table 1.

  About the obtained patch, the retention strength of the paste layer was measured as 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 peel adhesive strength (g / 25 mm) was measured according to the 180 ° peel test specified in JIS Z0237 (2009), and the addition of the peel adhesive strength of the three test pieces was measured. The average value was defined as the adhesive strength of the patch.

[Storage stability (cold flow)]
One specimen (area 3 cm ² ) was obtained by cutting an arbitrary part of the patch. The test piece was sealed in a flat patch-shaped packaging material having a flat square shape with a side of 5 cm, and stored at 60 ° C. for 1 week, and then the cold flow was visually evaluated based on the following criteria.
−: The plaster layer did not protrude.
+/-: There was a slight protrusion in a part of the plaster layer.
+: The paste layer protruded over the entire circumference of the test piece.
++: The plaster layer protruded by 0.5 mm or more.

[Storage stability (drug concentration)]
Six test pieces (area 3 cm ² ) were obtained by cutting any part of the patch. The test piece was enclosed in a light-shielding patch packaging material having a flat square shape with a side of 5 cm, 3 pieces were stored at 4 ° C., and the remaining 3 pieces were stored at 60 ° C. for 2 weeks. After storage, the weight Wt of each test piece is measured, and the release liner is removed. Then, the drug in the plaster layer is extracted using an extract (ethyl acetate: methanol = 3: 2), and HPLC is used. The drug weight Wr in the patch was quantified. The support was washed with ethyl acetate or toluene and dried, and the combined weight Wp of the release liner and the support 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 value of the drug concentration in the paste layer of the three test pieces stored at 4 ° C. is C ₄ , and the arithmetic average value of the drug concentration in the paste layer of the three test pieces stored at 60 ° C. Was C _60, and the residual rate of the drug was calculated using the following formula (2).
Residual rate of drug (%) = 100 × C ₆₀ / C ₄ Formula (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 (6)

A support;
A plaster layer containing an acrylic pressure-sensitive adhesive layered and integrated on one surface of the support and having a drug and a crosslinking agent content of 0.1% by mass or less, and a resin having a softening point of 80 ° C. or higher; A patch comprising the following:   The patch according to claim 1, wherein the resin having a softening point of 80 ° C or higher has a weight average molecular weight of 400 to 10,000.   The patch according to claim 1 or 2, comprising 20 to 80 parts by mass of a resin having a softening point of 80 ° C or higher with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive.   The adhesive patch according to any one of claims 1 to 3, wherein the holding power of the acrylic adhesive is 60 minutes or more.   The adhesive patch according to any one of claims 1 to 4, which contains 10 to 50 parts by mass of a drug with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive.   The adhesive patch according to any one of claims 1 to 5, wherein the holding power of the plaster layer is 55 minutes or less.