WO2017034027A1 - Adhesive patch - Google Patents

Abstract

The present invention provides an adhesive patch that is capable of exhibiting excellent tackiness when adhered to the skin and reduces peeling from the skin once adhered thereto. This adhesive patch is characterized by including: a support body; and an adhesive layer that is integrally laminated upon one surface of the support body and includes an acrylic adhesive, polyisobutylene having a weight average molecular weight of 40000–400000, and a drug, with the content ratio of the polyisobutylene and the acrylic adhesive (mass of the polyisobutylene/mass of the acrylic adhesive) being 0.4–0.8.

Description

Patch

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

Traditionally, patches have been used to transdermally absorb drugs into the body. The patch generally includes a support and an adhesive layer containing an adhesive and a drug. As the pressure-sensitive adhesive, an acrylic pressure-sensitive adhesive, a rubber pressure-sensitive adhesive, a silicone pressure-sensitive adhesive, and the like are used. Among these, since the function and the transdermal absorption performance can be selected depending on the combination of the monomers, an acrylic pressure-sensitive adhesive is often used (for example, Patent Document 1).

Patent Document 2 includes a support and a pressure-sensitive adhesive layer disposed on the support and containing a pressure-sensitive adhesive base and a drug. The pressure-sensitive adhesive base has a carboxyl group and a hydroxyl group in the molecule. An acrylic polymer substantially free of rubber and a rubber polymer are contained, the acrylic polymer is 2-ethylhexyl acrylate / vinyl acetate copolymer, and the rubber polymer is styrene- A patch is proposed in which the isoprene-styrene block copolymer and polyisobutylene are at least one selected from the group consisting of basic drugs and pharmacologically acceptable salts thereof. ing.

Japanese Patent No. 4724368 Japanese Patent No. 4261911

The patch according to Patent Document 2 can exhibit sufficient tack when applied to the skin. However, with the movement of the human body after application, there is a problem that the patch applied to the skin easily peels from the skin. Therefore, a patch that can be stably applied to the skin for a long period of time regardless of the movement of the human body is desired.

An object of the present invention is to provide a patch that can exhibit an excellent tack when applied to the skin and that has reduced peeling from the skin during application. Therefore, the patch of the present invention can be stably applied to the skin over a long period of time, and the drug can be stably percutaneously absorbed into the body.

The patch of the present invention comprises a support, laminated and integrated on one surface of the support, and contains an acrylic pressure-sensitive adhesive, a polyisobutylene having a weight average molecular weight of 40,000 to 400,000, and a drug, and the polyisobutylene and And a pressure-sensitive adhesive layer having a content ratio of the acrylic pressure-sensitive adhesive (polyisobutylene / acrylic pressure-sensitive adhesive) of 0.4 to 0.8.

According to the present invention, it is possible to provide a patch that can exhibit an excellent tack to the skin at the time of application and has reduced peeling from the skin during application.

The patch of the present invention includes a support and a pressure-sensitive adhesive layer laminated and integrated on one surface of the support.

[Adhesive layer]
The pressure-sensitive adhesive layer contains an acrylic pressure-sensitive adhesive, polyisobutylene and a drug.

(Acrylic adhesive)
The acrylic pressure-sensitive adhesive is not particularly limited as long as it is a pressure-sensitive adhesive conventionally used in patches. As an acrylic adhesive, the acrylic polymer formed by polymerizing the monomer containing an alkyl (meth) acrylate is mentioned. The alkyl (meth) acrylate preferably does not have a functional group other than an ethylenically unsaturated double bond and an ester bond (—COO—). Moreover, it is preferable that the hydrogen atom of the alkyl group of alkyl (meth) acrylate is not substituted by the functional group. Examples of such a functional group include a hydroxyl group, an amino group, a carboxy group (—COOH), and a halogen atom. In addition, (meth) acrylate means an acrylate or a methacrylate. An acrylic polymer may be used independently or may use 2 or more types together.

Since polyisobutylene is incompatible with the acrylic adhesive, the acrylic adhesive and polyisobutylene do not form a single phase in the adhesive layer, but each phase is separated and exists as an independent phase. .

The acrylic pressure-sensitive adhesive contains an acrylic polymer obtained by polymerizing a monomer containing an alkyl (meth) acrylate, and the alkyl (meth) acrylate contains an ethylenically unsaturated double bond and an ester bond (—COO). When there is no functional group other than-), or when the hydrogen atom of the alkyl group of the alkyl (meth) acrylate is not substituted by the functional group, the acrylic pressure-sensitive adhesive and the polyisobutylene have a micro phase separation structure. Mix well while removing. Even when a force is applied to the patch to cause the patch to peel from the skin due to the movement of the human body, the micro-dispersed polyisobutylene aggregates and breaks down over the entire surface of the adhesive layer. While pulling the thread against the skin. The polyisobutylene in the form of a thread prevents the pressure-sensitive adhesive layer from peeling off from the skin surface, and returns the pressure-sensitive adhesive layer to the state of being stuck to the skin surface by elastic restoring force. Therefore, the patch can maintain a state of being stably adhered over a long period of time regardless of the movement of the human body.

The number of carbon atoms in the alkyl group of the alkyl (meth) acrylate is preferably 1 to 16, more preferably 1 to 14, particularly preferably 2 to 14, and most preferably 2 to 12.

Examples of the alkyl (meth) acrylate having an alkyl group having 1 to 16 carbon atoms include methyl (meth) acrylate, ethyl (meth) acrylate, n-propyl (meth) acrylate, isopropyl (meth) acrylate, n-butyl ( (Meth) acrylate, isobutyl (meth) acrylate, 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, and hydroxypropyl (meth) Acrylate and the like. As the alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group, dodecyl (meth) acrylate, n-octyl (meth) acrylate, and 2-ethylhexyl (meth) acrylate are preferable, and dodecyl (meth) acrylate and 2 -Ethylhexyl (meth) acrylate is more preferred, dodecyl methacrylate and 2-ethylhexyl (meth) acrylate are particularly preferred, dodecyl methacrylate, 2-ethylhexyl acrylate and 2-ethylhexyl methacrylate are particularly preferred. Alkyl (meth) acrylate may be used independently or may use 2 or more types together.

The acrylic polymer is an acrylic polymer obtained by copolymerizing the alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group and the alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group. A copolymer is preferred. It is necessary that the alkyl (meth) acrylate having 1 to 16 carbon atoms in the alkyl group is different from the alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group.

Examples of the alkyl (meth) acrylate having 3 to 16 carbon atoms in the alkyl group include n-propyl (meth) acrylate, n-butyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylbutyl (meth) acrylate, Examples include isooctyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, decyl (meth) acrylate, dodecyl (meth) acrylate, and tridecyl (meth) acrylate. Of these, dodecyl (meth) acrylate is preferable.

As the acrylic copolymer, an acrylic copolymer obtained by copolymerizing a monomer containing n-octyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, and dodecyl (meth) acrylate is preferable. An acrylic copolymer obtained by copolymerizing a monomer containing ethylhexyl (meth) acrylate and dodecyl (meth) acrylate is more preferable, and a single amount containing dodecyl methacrylate, 2-ethylhexyl acrylate, and 2-ethylhexyl methacrylate An acrylic copolymer obtained by copolymerizing the body is particularly preferred.

The content of the alkyl (meth) acrylate component having 1 to 16 carbon atoms of the alkyl group in the acrylic copolymer is preferably 40% by mass or more, more preferably 45 to 100% by mass, and 45 to 95% by mass. Particularly preferred.

The content of the alkyl (meth) acrylate having 3 to 16 carbon atoms of the alkyl group in the acrylic copolymer is preferably less than 60% by mass, more preferably 1 to 55% by mass, and particularly preferably 5 to 55% by mass. preferable.

The monomer of the acrylic copolymer may contain other monomers other than alkyl (meth) acrylate. Examples of other monomers include 1-vinyl-2-pyrrolidone, acrylamide, dimethylacrylamide, acrylonitrile, dimethylaminoethyl (meth) acrylate, t-butylaminoethyl (meth) acrylate, vinyl acetate, and vinyl propionate. Etc. In addition, (meth) acrylic acid means acrylic acid or methacrylic acid.

The acrylic polymer may be polymerized by a conventionally known method. 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, if necessary, a crosslinking agent are supplied to the reactor and heated at a temperature of 60 to 80 ° C. for 4 to 48 hours. The monomer is radically polymerized.

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.

The content of the acrylic pressure-sensitive adhesive in the pressure-sensitive adhesive layer is preferably 35% by mass or more, more preferably 40% by mass or more, and particularly preferably 45% by mass or more. 65 mass% or less is preferable, as for content of the acrylic adhesive in an adhesive layer, 60 mass% or less is more preferable, and 55 mass% or less is especially preferable. When the content of the acrylic pressure-sensitive adhesive is 35% by mass or more, the pressure-sensitive adhesive layer can exhibit more excellent tack on the skin. When the content of the acrylic pressure-sensitive adhesive is 65% by mass or less, a necessary amount of drug can be easily added to the pressure-sensitive adhesive layer.

The solubility parameter of the acrylic pressure-sensitive adhesive is preferably 8.5 to 10 (cal / cm ³ ) ^1/2, more preferably 8.7 to 9.5 (cal / cm ³ ) ^1/2. . When the solubility parameter of the acrylic pressure-sensitive adhesive is 8.5 (cal / cm ³ ) ^1/2 or more, the acrylic pressure-sensitive adhesive and polyisobutylene form a micro phase separation structure. When the solubility parameter of the acrylic pressure-sensitive adhesive is 10 (cal / cm ³ ) ^1/2 or less, the acrylic pressure-sensitive adhesive and polyisobutylene are mixed well in the pressure-sensitive adhesive layer while taking a micro phase separation structure. is doing. Therefore, even when a force for peeling the patch from the skin is applied to the patch, the polyisobutylene pulls the thread on the entire surface of the pressure-sensitive adhesive layer, and the patch is well prevented from peeling from the skin surface.

A solubility parameter (solubility parameter) is the square root of density (cal / cm ³ ) per unit volume (cm ³ ) of cohesive energy (cal) between molecules, as defined by J. H. Hildebrand. Specifically, the solubility parameter δ is determined by the following formula (1).
δ = (E / V) ^1/2 (1)
(In the formula, δ is a solubility parameter [(cal / cm ³ ) ^1/2 ], E is molar cohesive energy (cal), and V is molar volume (cm ³ / mol).)

For the solubility parameter, for example, refer to the values described in “Solubility Parameter Application Examples” (Akitoshi Taniguchi, Information Organization Co., Ltd., March 15, 2007, p.276-282). You can also.

Note that the solubility parameter of the acrylic pressure-sensitive adhesive is the square root of the sum of the values obtained by multiplying the weight percentage of each monomer by the square of the solubility parameter of each monomer. Specifically, it is calculated | required by following formula (2).
δ _A = [(φ ₁ × δ ₁ ² + φ ₂ × δ ₂ ² +... + φ _n × δ _n ² ) / 100] ^1/2 (2)
(In the formula, δ _A is the solubility parameter [(cal / cm ³ ) ^1/2 ] of the acrylic pressure-sensitive adhesive.) Φ _n is the weight percentage (mass%) of the n-th monomer among all monomers. δ _n is the solubility parameter [(cal / cm ³ ) ^1/2 ] of the n-th monomer, where n is an integer representing the number of types of monomers.)

(Polyisobutylene)
The pressure-sensitive adhesive layer contains polyisobutylene. In the pressure-sensitive adhesive layer, polyisobutylene does not form a single phase with the acrylic pressure-sensitive adhesive without being compatible with the acrylic pressure-sensitive adhesive, and exists as an independent phase. And polyisobutylene has rubber elasticity.

The skin surface changes with the movement of the human body. Due to the movement of the human body, a peeling force for peeling the patch from the skin surface may be applied to the patch stuck to the skin surface. Even if the pressure-sensitive adhesive layer tends to float from the skin surface due to this peeling force, the polyisobutylene is in a state where a thread is pulled between the pressure-sensitive adhesive layer and the skin surface. The thread-like polyisobutylene functions to prevent the pressure-sensitive adhesive layer from detaching from the skin surface and to return the pressure-sensitive adhesive layer that is about to leave the skin surface by elastic restoring force to the skin surface. As a result, the pressure-sensitive adhesive layer maintains a state adhered to the skin surface. Therefore, the pressure-sensitive adhesive layer reliably maintains the state of sticking to the skin surface regardless of the movement of the human body, and the patch maintains the state of being securely applied to the skin surface regardless of the movement of the skin after application. To do.

The weight average molecular weight Mw of polyisobutylene is 40,000 to 400,000, preferably 60000 to 150,000, and more preferably 65,000 to 100,000. When the weight average molecular weight of the polyisobutylene is 40000 or more, even if the pressure-sensitive adhesive layer tends to float from the skin surface, it becomes a thread between the pressure-sensitive adhesive layer and the skin surface, and the patch is attached to the skin surface. Make sure to maintain the state. When the weight average molecular weight of the polyisobutylene is 400000 or less, the thread-like polyisobutylene temporarily formed between the pressure-sensitive adhesive layer and the skin surface has elasticity necessary for returning the pressure-sensitive adhesive layer to the skin surface. Since it expresses, it is preferable. In addition, the weight average molecular weight of polyisobutylene says the polystyrene conversion value measured by a gel permeation chromatography (GPC) method.

When the polyisobutylene contains a plurality of types of polyisobutylene, the weight average molecular weight Mw of the polyisobutylene refers to a value calculated based on the following formula (3).
Mw = [M ₁ × W ₁ + M ₂ × W ₂ +... + Mn × Wn] / 100 (3)
(Where Mw is the weight average molecular weight of polyisobutylene; Mn is the weight average molecular weight of the nth polyisobutylene in the total polyisobutylene; Wn is the weight percentage of the nth polyisobutylene in the total polyisobutylene ( N is an integer representing the number of types of polyisobutylene.)

The solubility parameter of polyisobutylene is preferably 7.1 to 8.3 (cal / cm ³ ) ^1/2 . When the solubility parameter of polyisobutylene is 7.1 to 8.3 (cal / cm ³ ) ^1/2 , the acrylic adhesive and polyisobutylene take a micro phase separation structure in the adhesive layer. Mix well. Therefore, even when a force for peeling the patch from the skin is applied to the patch, the polyisobutylene pulls the thread on the entire surface of the pressure-sensitive adhesive layer, and the patch is well prevented from peeling from the skin surface. In addition, the solubility parameter of polyisobutylene can be measured by the same method as the case of an acrylic adhesive.

The absolute value of the difference between the solubility parameter of the acrylic adhesive and the solubility parameter of polyisobutylene is preferably 0.9 to 2.5 (cal / cm ³ ) ^1/2 , 1.1 to 1.9 ( cal / cm ³ ) ^1/2 is more preferable. When the absolute value of the difference between the solubility parameter of the acrylic adhesive and the solubility parameter of polyisobutylene is 0.9 to 2.5 (cal / cm ³ ) ^1/2 , The pressure-sensitive adhesive and polyisobutylene can be well mixed while taking a micro phase separation structure. Therefore, even when a force for peeling the patch from the skin is applied to the patch, the polyisobutylene pulls the thread on the entire surface of the pressure-sensitive adhesive layer, and the patch is well prevented from peeling from the skin surface.

In the pressure-sensitive adhesive layer, the content ratio of polyisobutylene and acrylic pressure-sensitive adhesive (mass of polyisobutylene / weight of acrylic pressure-sensitive adhesive) is 0.4 to 0.8, preferably 0.5 to 0.7, 0.55 to 0.65 is more preferable. When the content ratio of the polyisobutylene and the acrylic pressure-sensitive adhesive is 0.4 or more, the patch can be stably adhered to the skin surface regardless of the movement of the human body. When the content ratio of the polyisobutylene and the acrylic pressure-sensitive adhesive is 0.8 or less, the pressure-sensitive adhesive layer can exhibit more excellent tack to the skin.

The content of polyisobutylene in the pressure-sensitive adhesive layer is preferably 15 to 40% by mass, more preferably 20 to 38% by mass, and particularly preferably 25 to 36% by mass. When the content of polyisobutylene in the pressure-sensitive adhesive layer is 15% by mass or more, the patch can be stably adhered to the skin surface regardless of the movement of the human body. When the content of polyisobutylene in the pressure-sensitive adhesive layer is 40% by mass or less, the pressure-sensitive adhesive layer can exhibit more excellent tack to the skin.

(Plasticizer)
The pressure-sensitive adhesive layer preferably contains a plasticizer. It is preferable that the plasticizer is compatible with both the acrylic pressure-sensitive adhesive and the polyisobutylene because the pressure-sensitive adhesive layer exhibits a better tack with respect to the skin. When polyisobutylene is contained in the pressure-sensitive adhesive layer, the tackiness of the pressure-sensitive adhesive layer with respect to the skin is reduced as compared with the case where polyisobutylene is not contained in the pressure-sensitive adhesive layer. By including a plasticizer in the pressure-sensitive adhesive layer, the acrylic pressure-sensitive adhesive can be plasticized and the anchoring property of the pressure-sensitive adhesive layer to the skin surface can be improved. Thereby, when sticking a patch on the skin surface, the adhesive layer can exhibit an excellent tack to the skin, and the patch can be reliably stuck to the skin. Therefore, by using a combination of polyisobutylene and a plasticizer, the patch can be firmly attached to the skin surface, and the patch can be stably applied after the application regardless of the movement of the human body. Can be attached to the skin surface.

Examples of the plasticizer include esters such as isopropyl myristate, decyl oleate, isopropyl adipate, glyceryl tricaprylate, glyceryl tricaprate, glyceryl tri (caprylate / caprate); myristyl alcohol, cetanol, octyldodecanol, 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. As the plasticizer, esters and liquid paraffin are preferable, and esters of monovalent carboxylic acid and monohydric alcohol and liquid paraffin are more preferable. Examples of the monovalent carboxylic acid include myristic acid and oleic acid. Examples of the monohydric alcohol include isopropyl alcohol, decyl alcohol, myristyl alcohol, cetanol, octyldodecanol, isostearyl alcohol, stearyl alcohol and the like. In addition, a plasticizer may be used independently or may use 2 or more types together.

In the pressure-sensitive adhesive layer, the content ratio (plasticizer mass / polyisobutylene mass) of the plasticizer and polyisobutylene is preferably 2 or less, more preferably 0.4 or less, and particularly preferably 0.35 or less. When the content ratio of the plasticizer and polyisobutylene is 2 or less, the filamentous polyisobutylene that is temporarily formed between the adhesive layer and the skin surface is necessary to restore the adhesive layer to the skin surface. It is preferable because it exhibits excellent elasticity. The content ratio of the plasticizer to the polyisobutylene (the mass of the plasticizer / the mass of the polyisobutylene) is preferably 0.1 or more, and more preferably 0.15 or more. When the content ratio of the plasticizer and polyisobutylene is 0.1 or more, even if the distance between the adhesive layer and the skin surface increases, the polyisobutylene pulls the thread, and the adhesive layer is more securely attached to the skin surface. Return to.

The content of the plasticizer in the pressure-sensitive adhesive layer is preferably 0.1 to 35% by mass, more preferably 1 to 15% by mass, and particularly preferably 2 to 10% by mass. When the content of the plasticizer is 0.1% by mass or more, the pressure-sensitive adhesive layer can exhibit excellent tack to the skin. It is preferable for the content of the plasticizer to be 35% by mass or less because cold flow of the pressure-sensitive adhesive layer during storage can be suppressed.

The solubility parameter of the plasticizer is preferably 6.5 to 9.2 (cal / cm ³ ) ^1/2, more preferably 6.5 to 8.4 (cal / cm ³ ) ^1/2 , and 6.7 ˜8.2 (cal / cm ³ ) ^1/2 is particularly preferred, and 7.0 to 8.0 (cal / cm ³ ) ^1/2 is most preferred. When the solubility parameter of the plasticizer is 6.5 to 9.2 (cal / cm ³ ) ^1/2 , the plasticizer is well compatible with both the acrylic adhesive and polyisobutylene, The pressure-sensitive adhesive layer can exhibit better tack. In addition, the solubility parameter of a plasticizer means the value measured in the same way as the solubility parameter of an acrylic adhesive.

(Drug)
The pressure-sensitive adhesive layer contains a drug. Any drug may be used as long as it can be absorbed transdermally. For example, Alzheimer's drugs such as donepezil, rivastigmine, galantamine, tacrine, and memantine; Parkinson's disease drugs such as selegiline and rotigotine; Anti-inflammatory drugs such as diclofenac, indomethacin, and ethyl salicylate.

The drug is preferably a liquid drug that is liquid at 30 ° C. and has a plasticizing effect. Examples of such liquid drugs include rivastigmine, selegiline, memantine, and ethyl salicylate. According to these liquid drugs, the acrylic adhesive can be plasticized to further improve the anchoring property of the adhesive layer to the skin surface. Thereby, when sticking a patch, the adhesive layer can exhibit the tack which was more excellent with respect to skin.

The content of the drug in the pressure-sensitive adhesive layer is preferably 1 to 40 parts by weight, more preferably 1 to 30 parts by weight, and particularly preferably 5 to 25 parts by weight with respect to 100 parts by weight of the acrylic pressure-sensitive adhesive. If the drug content is low, the drug blood concentration may not be improved to the desired range. In addition, if the content of the drug is high, excessive drug may be wasted.

(Other additives)
The pressure-sensitive adhesive layer may contain other additives in addition to the above-mentioned acrylic pressure-sensitive adhesive, polyisobutylene and plasticizer. Examples of other additives include absorption promoters, stabilizers, fillers, and the like.

The filler is used to adjust the shape retention of the pressure-sensitive adhesive layer. Examples of the filler include inorganic fillers such as silicic anhydride, titanium oxide, and zinc oxide; organometallic salts such as calcium carbonate and magnesium stearate; cellulose such as lactose, crystalline cellulose, ethyl cellulose, and low-substituted hydroxypropyl cellulose. Derivatives and the like.

The content of the filler in the pressure-sensitive adhesive layer is preferably 5 parts by mass or less and more preferably 2 parts by mass or less with respect to 100 parts by mass of the acrylic pressure-sensitive adhesive. When the content of the filler is high, the tackiness of the pressure-sensitive adhesive layer may be lowered.

The thickness of the pressure-sensitive adhesive layer is not particularly limited, but is preferably 10 to 250 μm, more preferably 20 to 200 μm, and particularly preferably 40 to 150 μm. A thin adhesive layer may not contain a sufficient amount of drug. In addition, a thick adhesive layer may reduce the cohesive force.

[Support]
In the patch of the present invention, the above-mentioned pressure-sensitive adhesive layer 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 pressure-sensitive adhesive 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 these, polyethylene terephthalate is particularly preferable because it can prevent loss of the drug from the pressure-sensitive adhesive layer even if it is a volatile drug.

Examples of the material constituting the nonwoven fabric include polyethylene, polypropylene, ethylene-vinyl acetate copolymer, ethylene-methyl (meth) acrylate 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.

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 pressure-sensitive adhesive layer so as to be peeled off. The release liner is used for preventing loss of the drug in the pressure-sensitive adhesive layer and protecting the pressure-sensitive adhesive layer.

Examples of the release liner include paper and resin film. Examples of the resin constituting the resin film include polyethylene terephthalate, polyethylene, polypropylene, polyvinyl chloride, and polyvinylidene chloride. It is preferable that the surface of the release liner facing the pressure-sensitive adhesive layer is subjected to a mold release treatment.

[Manufacturing method of patch]
As a method for producing the patch of the present invention, for example, (1) a pressure-sensitive adhesive layer solution containing an acrylic pressure-sensitive adhesive and polyisobutylene, a drug and a solvent is applied to one surface of the support and then dried. A pressure-sensitive adhesive layer is laminated and integrated on one surface of the body, and if necessary, a release liner is laminated on the pressure-sensitive adhesive layer so that the surface where the release treatment of the release liner is performed faces the pressure-sensitive adhesive layer. Method (2) The pressure-sensitive adhesive layer solution is applied onto the release liner surface, and dried to form a pressure-sensitive adhesive layer on the release liner, which is then supported by the pressure-sensitive adhesive layer. Examples include a method of stacking and integrating the body.

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

Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited thereto.

[Preparation of acrylic adhesive A]
Acrylic adhesive A was prepared as follows. 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 was added to 50 parts by weight of ethyl acetate, and these were stirred to obtain a reaction solution. . Next, the reaction solution was supplied to a 40 liter polymerization machine, and the inside of the polymerization machine was set to a nitrogen atmosphere at 80 ° C. On the other hand, 0.5 parts by mass of benzoyl peroxide was dissolved in 50 parts by mass of cyclohexane to obtain a polymerization initiator solution. Then, the monomer is copolymerized while adding the polymerization initiator solution to the reaction solution over 24 hours, and after completion of the polymerization, ethyl acetate is further added to the reaction solution, and the content of the acrylic pressure-sensitive adhesive A is 35% by mass. A solution was obtained. The solubility parameter of the acrylic pressure-sensitive adhesive A was 9.0 (cal / cm ³ ) ^1/2 .

(Examples 1 to 19 and Comparative Examples 1 to 4)
Acrylic pressure-sensitive adhesive A, ethyl cellulose (coagulation modifier, solubility parameter: 10.3 (cal / cm ³ ) ^1/2 , trade name “Etocel” manufactured by Dow Chemical Co.), polyisobutylene A (weight average molecular weight: 340000, Solubility parameter: 7.6 (cal / cm ³ ) ^1/2 , product name “Oppanol B50” manufactured by BASF), polyisobutylene B (weight average molecular weight: 200000, solubility parameter: 7.6 (cal / cm ³⁾ ) ^1/2 , a product name “OPPANOL B30” manufactured by BASF), polyisobutylene C (weight average molecular weight: 75000, solubility parameter: 7.6 (cal / cm ³ ) ^1/2 , a product name “OPPANOL” manufactured by BASF B15 "), polyisobutylene D (weight average molecular weight: 51000, solubility parameter: 7.6 ( al / cm ^{3) 1/2,} BASF Corporation, trade name "Oppanol B12"), liquid paraffin (solubility ^{parameter: 7.1 (cal / cm 3)} 1/2, Kaneda Corporation, trade name "Haikoru M-72 )), Isopropyl myristate (solubility parameter: 8.0 (cal / cm ³ ) ^1/2 ), octyldodecanol (solubility parameter: 8.9 (cal / cm ³ ) ^1/2 ), diisopropyl adipate (Solubility parameter: 8.5 (cal / cm ³ ) ^1/2 ), tri (caprylic acid / capric acid) glyceryl (solubility parameter: 9.1 (cal / cm ³ ) ^1/2 ) and rivastigmine, Each mixture was blended so as to have the blending amounts shown in Tables 1 to 3, and a mixture was obtained. After adding ethyl acetate and toluene so that the solid content was 25% by mass, And mixed until homogeneous these to prepare a pressure-sensitive adhesive layer solution. In the table, the solubility parameter is expressed as “SP”. Tri (caprylic acid / capric acid) glyceryl is a triester of glycerin and carboxylic acid containing caprylic acid and capric acid.

Next, a polyethylene terephthalate film (thickness 38 μm) subjected to silicone release treatment was prepared as a release liner. A laminate in which a pressure-sensitive adhesive layer (thickness: 100 μm) is formed on the silicone release treatment surface of the release liner by applying a pressure-sensitive adhesive layer solution to the silicone release treatment surface of the release liner and drying at 80 ° C. for 15 minutes. Got the body.

A polyethylene terephthalate film (thickness 25 μm) was prepared as a support. The support and the laminate were overlapped so that the support and the pressure-sensitive adhesive layer faced each other, and the adhesive layer of the laminate was laminated and integrated on one surface of the support to obtain a patch.

[Evaluation]
The patches immediately after obtained in Examples and Comparative Examples were subjected to 180 ° peeling test, ball tack test, probe tack test and storage test (cold flow resistance) in the following manner, and the obtained results were shown It is shown in the column of “initial” 1 to 3.

Suppose the patch (after use) immediately after peeling off the skin after the patch was applied to the skin for 20 hours. Specifically, for a patch containing 10 parts by mass of rivastigmine in the pressure-sensitive adhesive layer, a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 2 parts by mass was prepared. For a patch containing 11 parts by mass of rivastigmine in the pressure-sensitive adhesive layer, a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 3 parts by mass was prepared. For a patch containing 12 parts by mass of rivastigmine in the pressure-sensitive adhesive layer, a patch (after use) in which the content of rivastigmine in the pressure-sensitive adhesive layer was 3 parts by mass was prepared. The patch (after use) was subjected to a 180 ° peel test, a ball tack test, and a probe tack test in the following manner, and the obtained results are shown in the “API low concentration” column of Tables 1 to 3.

(180 ° peel test (adhesive strength))
Three test pieces (22.5 mm wide × 15 mm long) were obtained by cutting any part of the patch. For each test piece, the peel adhesive strength (g / 25 mm) was measured in accordance with the 180 ° peel test specified in JIS Z0237 (2009), and the arithmetic average values thereof are shown in Tables 1 to 3. Indicated.

(Ball tack test (tack))
Three test pieces (22.5 mm wide × 15 mm long) were obtained by cutting any part of the patch. About each test piece, the maximum ball number was measured according to the inclination type ball tack test prescribed | regulated to JISZ0237 (2009). Tables 1 to 3 show the arithmetic average values of the maximum ball numbers of the three test pieces.

(Probe tack test)
Three test pieces (area 3 cm ² ) were obtained by cutting an arbitrary part of the patch. About each test piece, the probe was press-bonded to the surface of the pressure-sensitive adhesive layer of the test piece with a pressure of 1000 g for 3 seconds using a probe tack tester (trade name “TA-500” manufactured by UBM). Next, the probe was pulled away from the pressure-sensitive adhesive layer at a speed of 0.01 mm / s, and the tensile force was continuously measured until the pressure-sensitive adhesive layer of the test piece and the probe were completely peeled to obtain a tensile peak. The area of the measured tensile peak is shown in Tables 1-3.

(Storage test (cold flow resistance))
One specimen (area 3 cm ² ) was obtained by cutting an arbitrary part of the patch. The test piece was encapsulated in a 5 cm × 5 cm flat rectangular transparent packaging material for patch, stored at 60 ° C. for 1 week, and then visually evaluated the cold flow based on the following criteria. The evaluation results are shown in Tables 1 to 3.
-: The adhesive layer did not protrude.
+/-: There was a slight protrusion in a part of the pressure-sensitive adhesive layer.
+: The pressure-sensitive adhesive layer protruded all around the test piece.
++: The adhesive layer protruded 0.5 mm or more.

(Cross-reference of related applications)
This application claims priority based on Japanese Patent Application No. 2015-168095 filed on Aug. 27, 2015, the disclosure of which is incorporated herein by reference in its entirety.

The patch of the present invention can exhibit an excellent tack to the skin at the time of application, and the peeling from the skin during the application is reduced, so that various drugs can be stably percutaneously absorbed and the drug administration effect can be obtained. It can be obtained stably.

Claims (4)

A support;
An acrylic pressure-sensitive adhesive, a polyisobutylene having a weight average molecular weight of 40,000 to 400,000, and a drug are laminated and integrated on one surface of the support, and the content ratio of the polyisobutylene and the acrylic pressure-sensitive adhesive (polyisobutylene) And a pressure-sensitive adhesive layer having a weight ratio of 0.4 to 0.8. The adhesive patch according to claim 1, wherein the pressure-sensitive adhesive layer further contains a plasticizer, and the content ratio of the plasticizer and polyisobutylene (the mass of the plasticizer / the mass of the polyisobutylene) is 2 or less. . The solubility parameter of the acrylic pressure-sensitive adhesive is 8.5 to 10 (cal / cm ³ ) ^1/2 and the solubility parameter of the plasticizer is 6.5 to 9.2 (cal / cm ³ ) ^1/2. The patch according to claim 2, wherein the patch is. The acrylic pressure-sensitive adhesive contains a polymer of a monomer containing an alkyl (meth) acrylate, and the alkyl (meth) acrylate does not have a functional group other than an ethylenically unsaturated double bond and an ester bond. The patch according to claim 1, wherein