JP5064234B2 - Adhesive base and transdermal patch - Google Patents

Description

  The present invention relates to an adhesive base and a transdermal absorption patch.

  In recent years, various transdermal patches that administer drugs to the living body through the skin surface have been developed. The pressure-sensitive adhesive layer constituting such a patch is usually formed from a mixture containing a medicinal component and a pressure-sensitive adhesive base mainly composed of a polymer. Recently, there is a tendency to increase the drug concentration and to contain a large amount of absorption enhancer for the purpose of improving transdermal absorption performance, thus ensuring adhesiveness and cohesion, which are important characteristics of patches. Therefore, a method of forming an adhesive layer with a crosslinked polymer is used. In addition, since the adhesive layer is generally a layered one, the adhesive base is required to have not only desired adhesive properties but also excellent film forming properties. In response to such a demand, for example, a technique has been devised in which a low molecular weight polymer and a crosslinking agent that crosslinks such a polymer are blended into an adhesive base, and this is formed into a layer and then crosslinked.

  By the way, a (meth) acrylic acid ester copolymer is useful as a component blended in an adhesive base because it has excellent adhesiveness. When the above-mentioned crosslinked polymer is formed using this copolymer, for example, a method using a crosslinking agent and a copolymer having a functional group that reacts with the crosslinking agent in the molecule has been proposed (for example, (See Patent Documents 1 to 3). However, in such a method, a highly reactive crosslinking agent such as a metal salt, an isocyanate compound, a metal alcoholate, or a metal chelate is used, and these compounds are likely to chemically react with the medicinal component. The drug transdermal absorbability tended to be impaired.

  Therefore, a method using an amine compound as a crosslinking agent has been proposed for the purpose of avoiding a chemical reaction with a medicinal component (see, for example, Patent Documents 4 and 5).

JP-A-57-176908 Japanese Patent Laid-Open No. 10-192390 JP-A-5-65224 JP 2004-35533 A JP 2002-535475 A

  However, recently, in the situation where a higher level of drug transdermal absorbability is required for transdermal patches, the cross-linking agents described in Patent Documents 4 and 5 are used. Even patches prepared in this manner are not necessarily sufficient for the following reasons, and there is room for further improvement.

  That is, according to the study by the present inventors, when a low molecular weight polyamine such as ethylenediamine is blended as a crosslinking agent, the drug (medicinal component) crystallizes over time and the transdermal absorbability of the drug decreases. Is known. In addition, when a polyamine having a long-chain alkylene group such as dodecamethylenediamine and having a large molecular weight is used, not only drug crystals are produced, but it is also difficult to ensure cohesiveness of the adhesive layer. It turns out.

  The present invention has been made in view of the above circumstances, and is capable of forming an adhesive layer sufficiently excellent in cohesiveness and capable of improving the transdermal absorbability of a drug and percutaneous absorption using the same The purpose is to provide a mold patch.

  As a result of diligent investigations to solve the above problems, the inventors of the present invention combined a polymer having a carboxyl group in the molecule with a polyamine compound having a specific structure as a crosslinking agent for crosslinking the polymer. By blending into the base, it is possible to form an adhesive layer with excellent cohesiveness, and in the formed adhesive layer, it is possible to sufficiently prevent the precipitation of drug crystals and improve the transdermal absorbability of the drug. As a result, the present invention has been completed.

  That is, the adhesive base of the present invention includes a polymer having a carboxyl group in the molecule and a crosslinking agent that crosslinks the polymer, and the crosslinking agent has an ester bond and / or an ether bond in the molecule. It is a compound containing two or more in total and containing in total at least two amino groups selected from the group consisting of primary amino groups, secondary amino groups and tertiary amino groups in the molecule. It is characterized by that.

Here, the “primary amino group” refers to —NH ₂ , the “secondary amino group” refers to —NH— (imino group), and the “tertiary amino group” refers to nitrogen It refers to a group represented by the following general formula (3) in which no hydrogen atom is bonded to the atom.

  According to such an adhesive base, it is possible to form an adhesive layer that is excellent in cohesion and does not easily precipitate drug crystals, even when a large amount of a medicinal ingredient is added or an absorption accelerator is further added. it can. This makes it possible to realize a transdermal patch having a higher level of drug transdermal absorbability than before.

  The reason why the above-described effect is exhibited by the adhesive base of the present invention is not necessarily clear, but the present inventors speculate as follows. First, the polymer chain network constituting the adhesive layer is generated when the carboxyl group of the polymer becomes a carboxyl ion, the amino group of the cross-linking agent becomes an ammonium ion, and ionic bonds with each other to form a crosslinking point. Conceivable. And the said crosslinking agent has two or more in the molecule | numerator the site | part which bridge | crosslinks the polymer which has a carboxyl group, and an ester bond and / or an ether bond. According to such a compound, even when a lipophilic unit such as an alkylene group is introduced between ester bonds, between ether bonds, or between an ester bond and an ether bond, the polymer is well crosslinked and adhered. It is considered that the cohesiveness of the layer can be sufficiently secured. In addition, the lipophilic unit can be introduced without impairing the cohesiveness and the crosslinking agent having an ester bond and / or an ether bond is blended to improve the property of solubilizing the drug in the adhesive layer. It is considered that the drug was sufficiently prevented from crystallizing in the adhesive layer.

  In the pressure-sensitive adhesive base of the present invention, the crosslinking agent is preferably a compound having a polyester structural unit having 2 to 100 ester bonds in the molecule.

  When the crosslinking agent has the polyester structural unit, it is possible to form an adhesive layer that has sufficient cohesiveness and is less likely to cause crystallization of the drug. Such an effect is exhibited by the fact that more lipophilic units can be introduced into the polymer chain network constituting the adhesive layer and that the ester chain can be contained in the polymer chain network at a high concentration. it is conceivable that.

  The cross-linking agent is a compound containing in total at least four amino groups selected from the group consisting of primary amino groups, secondary amino groups, and tertiary amino groups in the molecule. It is preferable. By using such a cross-linking agent, it is possible to achieve a higher level of cohesiveness of the formed adhesive layer and transdermal absorbability of the drug. As the reason why such an effect is obtained, the present inventors infer as follows.

  That is, as described above, in the polymer chain network constituting the adhesive layer, the carboxyl group of the polymer is a carboxyl ion, the amino group of the cross-linking agent is an ammonium ion, and each other is ionically bonded to form a crosslinking point. This is thought to be caused by And when the crosslinking agent which has four or more amino groups is mix | blended, since there exist four or more parts which can become ammonium ion in 1 molecule, the polymer chain network which has sufficient intensity | strength by more reliable bridge | crosslinking is obtained. It is considered that the flexibility of the polymer chain network is improved by the formation of the ammonium ion, which is a crosslinking point, and the exchange of the crosslinking point due to ion exchange with other amino groups. In such a polymer chain network, even if the amount of the crosslinking agent is further increased, a decrease in cohesion due to insufficient crosslinking can be sufficiently avoided, and the function of solubilizing the drug can be further enhanced. The present inventors infer that this is obtained.

  On the other hand, in the method using the conventional polyamine compound (hereinafter sometimes referred to as “conventional method”), an attempt is made to prevent the crystallization of the drug due to an excess amino group by increasing the blending amount of the crosslinking agent. The cohesive force of the adhesive layer is reduced due to insufficient crosslinking. In order to ensure the formation of a polymer chain network, if a polymer and a cross-linking agent are blended so that both ions are close to the equivalent, a polymer chain network with less flexibility is formed, so that the drug is crystallized. It cannot be prevented sufficiently. In addition, in the conventional method, it may be possible to increase the content ratio of the carboxyl group, but in this case, the glass transition temperature of the polymer chain network is increased and the adhesive layer becomes stiff, making it difficult to obtain a good feeling of use. .

  In the adhesive base of the present invention, the cross-linking agent is preferably a polyester / polyamine copolymer or a polyether / polyamine copolymer.

  In this case, the cohesiveness of the formed adhesive layer and the transdermal absorbability of the drug can be achieved at a higher level.

ここで、式（１）中、Ｒ^１は２価の有機基を示し、Ｒ^２は水素原子又は炭素数１〜１０のアルキル基を示し、ｎ１は２以上の整数を示す。

ここで、式（２）中、Ｒ^３は、３価の有機基を示し、Ｒ^４およびＲ^５はそれぞれ独立に、水素原子又は炭素数１〜１０のアルキル基を示し、ｎ２は２以上の整数を示す。Furthermore, the crosslinking agent is preferably a compound containing a structural unit represented by the following general formula (1) or the following general formula (2).

Here, in the formula (1), R ¹ represents a divalent organic group, R ² represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n1 represents an integer of 2 or more.

Here, in Formula (2), R ³ represents a trivalent organic group, R ⁴ and R ⁵ each independently represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n2 is 2 or more. Indicates an integer.

  When the crosslinking agent contains the above structural unit, the cohesiveness of the formed adhesive layer and the transdermal absorbability of the drug can be achieved at a higher level. Such an effect is considered to be produced because the above-described structural unit has an effect of suppressing the crystallization of the drug while the above-described movement of the crosslinking point becomes easier.

  The cross-linking agent is a compound having a total of 4 to 100 at least one amino group selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule. Preferably there is. Thereby, the crystallization of the drug can be more reliably prevented while enhancing the cohesiveness of the adhesive layer, and the transdermal absorption type patch which satisfies both the feeling of use and the transdermal absorbability of the drug at a higher level. Can be realized.

  Furthermore, it is preferable that the weight average molecular weight of the said crosslinking agent is 2000-20000. By using a cross-linking agent having a molecular weight in such a range, a highly flexible polymer chain network can be more reliably formed, and therefore the effect of preventing drug crystallization can be further improved. If the weight average molecular weight of the crosslinking agent is less than 2,000, it tends to be difficult to suppress crystallization of the drug. On the other hand, if it exceeds 20000, the compatibility with the polymer may decrease.

  In the adhesive base of the present invention, at least selected from the group consisting of a primary amino group, a secondary amino group and a tertiary amino group of the crosslinking agent with respect to the total number A of carboxyl groups of the polymer. The ratio (B / A) of the total number B of one amino group is preferably 1/50 to 2/1. As a result, the crystallization of the drug can be more reliably prevented while sufficiently securing the cohesiveness and adhesiveness of the adhesive layer, and the transdermal system satisfying both the feeling of use and the transdermal absorbability of the drug at a higher level. An absorptive patch can be realized. When (B / A) is less than 1/50, it tends to be difficult to ensure sufficient cohesiveness of the adhesive layer. When (B / A) exceeds 2/1, It tends to be difficult to ensure sufficient adhesiveness of the adhesive layer.

  In the adhesive base of the present invention, it is preferable that a (meth) acrylic acid ester copolymer is included as the polymer. According to such an adhesive base, it is possible to effectively exhibit the excellent adhesiveness possessed by the (meth) acrylic acid ester copolymer while sufficiently preventing the cohesiveness of the adhesive layer from decreasing and crystallization of the drug. Become.

  Further, the present invention is a transdermal absorption device comprising a support and an adhesive layer provided on at least one surface of the support and comprising any one of the adhesive bases of the present invention and a medicinal component. A mold patch is provided.

  According to the transdermal absorption patch of the present invention, an excellent feeling of use and a high level of medicinal effect can be obtained by having an adhesive layer formed by blending the adhesive base of the present invention.

  In the transdermal patch of the present invention, the medicinal component preferably contains a basic drug and / or a pharmaceutically acceptable salt of the basic drug.

  A polymer having a carboxyl group in the molecule can exhibit an appropriate cohesive force by performing sufficient cross-linking, and can improve the physical properties of the adhesive layer. There was a problem that the transdermal absorbability of the drug was lowered due to the influence of the group. In the conventional method using a polyamine compound, the carboxyl group is neutralized at the time of crosslinking, so that improvement in the transdermal absorbability of the drug has been expected. However, it is difficult to reach a sufficient level. That is, as described above, when a polymer and a crosslinking agent are blended so that the carboxyl group can be sufficiently neutralized, crystallization of the drug cannot be sufficiently prevented because a less flexible polymer chain network is formed, It is not possible to sufficiently improve the transdermal absorbability of the drug.

  On the other hand, according to the transdermal patch according to the present invention, since the adhesive layer contains the adhesive base of the present invention, the basic drug and / or the pharmaceutical of the basic drug is used. Even in the case of containing a salt that is acceptable, it is possible to sufficiently improve the transdermal absorbability of the drug while ensuring excellent cohesiveness.

  In the transdermal patch of the present invention, the amount of the crosslinking agent is preferably 1 to 30% by mass based on the total amount of the adhesive layer. If the blending amount is less than 1% by mass, it tends to be difficult to obtain an excellent feeling of use of the patch and a high level of medicinal effect. It tends to decrease, and a residue tends to occur.

  ADVANTAGE OF THE INVENTION According to this invention, the adhesive base which can form the adhesive layer which is excellent in cohesion sufficiently, and can improve the transdermal absorbability of a drug, and a transdermal absorption type | mold patch using the same can be provided.

It is a perspective view which shows suitable one Embodiment of the transdermal absorption type patch of this invention. It is a graph which shows transition of the drug permeation rate Flux in the skin permeation test of the patches prepared in Examples and Comparative Examples. It is a graph which shows transition of the chemical | medical agent penetration amount in the skin permeation test of the patch produced by the Example and the comparative example. It is a graph which shows transition of the drug permeation rate Flux in the skin permeation test of the patches prepared in Examples and Comparative Examples. It is a graph which shows transition of the chemical | medical agent penetration amount in the skin permeation test of the patch produced by the Example and the comparative example.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Percutaneous absorption type patch, 2 ... Support body, 3 ... Adhesive layer, 4 ... Release sheet.

  DESCRIPTION OF EMBODIMENTS Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the drawings.

<Transdermal absorption patch>
FIG. 1 is a perspective view showing a preferred embodiment of the transdermal absorption patch of the present invention. In FIG. 1, a transdermal absorption patch 1 is composed of a support 2, an adhesive layer 3 disposed on the support 2, and a release sheet 4 disposed on the adhesive layer 3.

  The pressure-sensitive adhesive layer 3 provided in the transdermal absorption patch 1 of the present embodiment is formed by blending the pressure-sensitive adhesive base, medicinal components, and other components as necessary according to the present invention.

  The adhesive base according to the present invention includes a polymer having a carboxyl group in the molecule and a cross-linking agent that cross-links the polymer, and the cross-linking agent has a total of 2 ester bonds and / or ether bonds in the molecule. It is a compound that contains at least one amino group selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule.

(Polymer having a carboxyl group in the molecule)
As the polymer having a carboxyl group in the molecule used in the present embodiment, for example, a monomer having a carboxyl group such as acrylic acid or methacrylic acid from the viewpoint that the adhesive property of the adhesive layer 3 can be easily changed according to the use. It is preferable to use a copolymer obtained by copolymerizing with other monomer components. Examples of the monomer having a carboxyl group include acrylic acid, methacrylic acid, maleic acid, fumaric acid, and itaconic acid. The carboxyl group of the copolymer forms a crosslinking point of the polymer chain network by reacting with a crosslinking agent described later.

  In this embodiment, it is preferable to use a (meth) acrylic acid ester copolymer. Since the (meth) acrylic acid ester copolymer does not have a double bond like a rubber polymer, it is stable against heat. Furthermore, various adhesive properties can be imparted by variously changing the alkyl group of the ester portion of the copolymer.

  Examples of the main monomer component of the (meth) acrylic acid ester copolymer include acrylic acid alkyl esters and methacrylic acid alkyl esters. As the alkyl group possessed by these esters, an alkyl group having 4 to 18 carbon atoms is preferred. Specifically, for example, butyl (meth) acrylate, hexyl (meth) acrylate, octyl (meth) acrylate such as 2-ethylhexyl acrylate, isononyl (meth) acrylate, decyl (meth) acrylate, lauryl (meth) acrylate and Examples include stearyl (meth) acrylate. The above monomers can be used alone or in combination of two or more. Moreover, it is preferable that the mixture ratio of the main monomer in a copolymer is 50-98 mol%.

  Examples of other copolymerization monomers include (meth) acrylic such as methyl acrylate, hydroxyethyl acrylate, hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, hydroxybutyl (meth) acrylate, and diethylaminoethyl (meth) acrylate. Examples include acid esters, (meth) acrylic amides such as isopropylacrylamide, vinyl pyrrolidone, vinyl acetate, vinyl alcohol, and styrene. These copolymerizable monomers may have a functional group for self-crosslinking. The above monomers can be used alone or in combination of two or more. Moreover, it is preferable that the mixture ratio of the said other copolymerization monomer in a copolymer is 0-50 mol%.

  The amount of the polymer blended is preferably in the range of 20 to 95% by mass, more preferably in the range of 30 to 80% by mass, based on the total amount of the adhesive layer 3. If the blending amount is less than 20% by mass, it tends to be difficult to obtain sufficient tackiness and cohesion, while if the blending amount exceeds 95% by mass, the tackiness is too high and causes skin irritation. It tends to be easier.

(Crosslinking agent)
At least one selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule, wherein the molecule contains two or more ester bonds and / or ether bonds in total Examples of the compound containing 2 or more amino groups in total include polyester / polyamine copolymers and polyether / polyamine copolymers.

  The polyester / polyamine copolymer includes a polyamine containing at least one amino group selected from the group consisting of a primary amino group, a secondary amino group and a tertiary amino group, and two ester bonds. Examples thereof include copolymers in which the above-mentioned polyester is bound. The type of bond between the polyamine and the polyester is not particularly limited, but is preferably a condensation polymer of the polyamine and the polyester.

ＰＥＳは、ポリエステル骨格を示す。Examples of the bond between polyamine and polyester include the following.

PES indicates a polyester skeleton.

ここで、式（１）中、Ｒ^１は２価の有機基を示し、Ｒ^２は水素原子又は炭素数１〜１０のアルキル基を示し、ｎ１は２以上の整数を示す。また、式（１）中、Ｒ^１は、置換基を有してもよいアルキレン基であることが好ましく、かかるアルキレン基は炭素数２〜４の分枝状又は直鎖状のアルキレン基であることがより好ましい。アルキレン基が置換基を有する場合、置換基が酸素原子を含むものであることが好ましく、メトキシ基及びエトキシ基などのアルコキシ基であることがより好ましい。また、式（１）中、Ｒ^２が、水素原子であることが好ましく、ｎ１が、２〜１００であることが好ましい。

ここで、式（２）中、Ｒ^３は、３価の有機基を示し、Ｒ^４およびＲ^５はそれぞれ独立に、水素原子又は炭素数１〜１０のアルキル基を示し、ｎ２は２以上の整数を示す。Ｒ^３は、−ＮＲ^４Ｒ^５以外の置換基を有していてもよく、かかる置換基は、酸素原子を含むものであることが好ましく、メトキシ基及びエトキシ基などのアルコキシ基であることがより好ましい。更に、式（２）中、Ｒ^３が、−ＮＲ^４Ｒ^５で置換された炭素数１〜１０の分枝状又は直鎖状のアルキレン基であることが好ましく、ｎ２が、２〜１００であることが好ましい。The copolymer preferably contains a structural unit represented by the following general formula (1) or the following general formula (2) as a polyamine.

Here, in the formula (1), R ¹ represents a divalent organic group, R ² represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n1 represents an integer of 2 or more. In Formula (1), R ¹ is preferably an alkylene group which may have a substituent, and the alkylene group is a branched or straight chain alkylene group having 2 to 4 carbon atoms. It is more preferable. When the alkylene group has a substituent, the substituent preferably contains an oxygen atom, and more preferably an alkoxy group such as a methoxy group and an ethoxy group. Further, in formula (1), ^{R 2} is preferably a hydrogen atom, n1 is preferably 2 to 100.

Here, in Formula (2), R ³ represents a trivalent organic group, R ⁴ and R ⁵ each independently represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n2 is 2 or more. Indicates an integer. R ³ may have a substituent other than —NR ⁴ R ⁵ , and such a substituent preferably contains an oxygen atom, and more preferably an alkoxy group such as a methoxy group and an ethoxy group. . Further, in formula (2), R ³ is preferably a branched or straight chain alkylene group having 1 to 10 carbon atoms substituted with —NR ⁴ R ⁵ , and n2 is 2 to 100. Preferably there is.

  By including the above structural unit, the cohesiveness, adhesiveness and transdermal absorbability of the drug can be achieved at a higher level.

ここで、式（４）中、Ｒ^６は、アルキレン基を示し、ｎ３は、２以上の整数を示す。また、式（４）中、Ｒ^６が、炭素数３〜６のアルキレン基であることが好ましく、ｎ３が、２〜１００であることが好ましい。

ここで、式（５）中、Ｒ^７及びＲ^８はそれぞれ独立に、炭素数１〜１０のアルキレン基を示し、ｎ４は、２以上の整数を示す。また、式（５）中、Ｒ^７が炭素数２〜１０のアルキレン基（より好ましくは、ジメチレン〜デカメチレン）、Ｒ^８が炭素数１〜１０のアルキレン基（より好ましくは、メチレン〜デカメチレン）であることが好ましく、ｎ４が２〜５０であることが好ましい。Moreover, it is preferable that the said copolymer contains the polyester structural unit of 2-100 ester bonds in a molecule | numerator from a viewpoint which suppresses precipitation of the crystal | crystallization of a drug over a long period of time. Examples of such a polyester structural unit include a structural unit represented by the following general formula (4) and a structural unit represented by the following general formula (5).

Here, in Formula (4), R ⁶ represents an alkylene group, and n3 represents an integer of 2 or more. In the formula (4), ^{R 6} is preferably an alkylene group having 3 to 6 carbon atoms, n3 is preferably 2 to 100.

Here, in Formula (5), R ⁷ and R ⁸ each independently represent an alkylene group having 1 to 10 carbon atoms, and n4 represents an integer of 2 or more. In Formula (5), R ⁷ is an alkylene group having 2 to 10 carbon atoms (more preferably, dimethylene to decamethylene), and R ⁸ is an alkylene group having 1 to 10 carbon atoms (more preferably, methylene to decamethylene). It is preferable that n4 is 2 to 50.

  Examples of the polyester / polyamine copolymer containing the structural unit represented by the general formula (4) as the polyester structure include those containing a hydrophilic segment such as poly (alkyleneimine) and poly (carbonylalkyleneoxy) ( And a copolymer having an amide bond with a lipophilic segment such as the structural unit represented by the general formula (4).

  The alkylene group of the poly (alkyleneimine) is preferably a branched or straight chain alkylene group having 2 to 4 carbon atoms, and more preferably an ethylene group.

  The hydrophilic segment preferably has an average molecular weight of 80 to 12000, more preferably 100 to 2000. If the average molecular weight of the segment is less than 80, it tends to be difficult to suppress crystallization of the drug, whereas if it exceeds 12000, the compatibility with the polymer may be lowered.

  The alkylene group of the poly (carbonylalkyleneoxy) is preferably an alkylene group having 3 to 6 carbon atoms, and more preferably a pentamethylene group. Poly (carbonylpentamethyleneoxy) groups can be derived by polymerizing ε-caprolactone. In this case, the polymerization degree of ε-caprolactone is preferably 2 to 100, more preferably 20 to 50. Note that the terminal of poly (carbonylalkyleneoxy) that is not bonded to poly (alkyleneimine) may have an alkyl group, an alkoxyalkyl group, a haloalkyl group, or an acyl group.

  In the polyester / polyamine copolymer, the content of poly (carbonylalkyleneoxy) relative to poly (alkyleneimine) is preferably 1 or more and more preferably 1.5 to 30 in terms of mass ratio. The molar ratio [poly (alkyleneimine)]: [poly (carbonylalkyleneoxy)] is preferably in the range of 1: 1 to 1: 4. In this case, the hydrophilic segment (polyamine) 1 has a structure in which 1 to 4 lipophilic segments (polyester) are bonded.

  Examples of the polyester / polyamine copolymer containing the structural unit represented by the general formula (5) as the polyester structure include poly (alkyleneimine) which is a hydrophilic segment, polyethylene adipate and polyethylene which are lipophilic segments. Examples thereof include copolymers in which sebacate, polypropylene adipate or polypropylene sebacate is amide-bonded.

  As the polyester / polyamine copolymer, a condensation polymer of a polyamine having two or more primary amino groups and a polyester can be used. Examples of the polyamine include epomin (registered trademark, Nippon Shokubai). As polyester, what is obtained by a well-known method can be used. The polyester / polyamine copolymer may be synthesized using a polyamine, a polyol and a polycarboxylic acid.

  In this embodiment, it is preferable to use a polyester / polyamine copolymer as a crosslinking agent. For example, Hypermer PS3, Hypermer KD-1 (both trade names, manufactured by Uniqema) are commercially available. Can be mentioned.

  The polyether / polyamine copolymer includes a polyamine containing at least one amino group selected from the group consisting of a primary amino group, a secondary amino group and a tertiary amino group, and an ether bond. Examples include a copolymer in which a polyether containing two or more is bonded.

  Examples of the polyamine of the copolymer include the polyamines in the polyester / polyamine copolymer described above.

ここで、式（６）中、Ｒ^９は、２価の有機基を示し、ｎ５は、２以上の整数を示す。また、式（６）中、Ｒ^９が、分枝状又は直鎖状のアルキレン基であることが好ましく、炭素数２〜１０の分枝状又は直鎖状のアルキレン基であることがより好ましい。また、式（６）中、ｎ５が、２〜１００であることが好ましく、２〜５０であることがより好ましい。The copolymer preferably has a polyether structural unit having 2 to 100 ether bonds in the molecule from the viewpoint of suppressing the precipitation of drug crystals over a longer period of time. As such a polyether structural unit, the structural unit shown by following General formula (6) is mentioned, for example.

Here, in Formula (6), R ⁹ represents a divalent organic group, and n5 represents an integer of 2 or more. In formula (6), R ⁹ is preferably a branched or linear alkylene group, more preferably a branched or linear alkylene group having 2 to 10 carbon atoms. . Moreover, in Formula (6), it is preferable that n5 is 2-100, and it is more preferable that it is 2-50.

  In this embodiment, the polyester / polyamine copolymer and the polyether / polyamine copolymer are at least selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule. It is preferable that 4 or more of 1 type of amino groups is included. By using such a compound, the cohesiveness, adhesiveness and transdermal absorbability of the formed adhesive layer 3 can be achieved at a higher level.

  The polyester / polyamine copolymer and the polyether / polyamine copolymer should have a melting point in the range of 40 to 80 ° C., solubility in organic solvents, compatibility with acrylate bases, and drugs. It is preferable in that it is excellent in solubilization.

  In addition, the crosslinking agent used in the present embodiment is a total of 4 to 100 at least one amino group selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule. It is preferable that it is a compound containing one piece. As a result, the crystallization of the drug can be more reliably prevented while enhancing the cohesiveness and adhesiveness of the adhesive layer 3, and the transdermal system satisfying both the feeling of use and the transdermal absorbability of the drug at a higher level. The absorption type patch 1 can be realized.

  Furthermore, it is preferable that the crosslinking agent used in this embodiment has a weight average molecular weight of 2000 to 20000. By using a crosslinking agent having a molecular weight in such a range, a highly flexible polymer chain network can be more reliably formed, and the effect of preventing drug crystallization can be further improved. If the weight average molecular weight of the crosslinking agent is less than 2,000, it tends to be difficult to suppress crystallization of the drug. On the other hand, if it exceeds 20000, the compatibility with the polymer may decrease.

  In the adhesive base of the present invention, at least selected from the group consisting of a primary amino group, a secondary amino group and a tertiary amino group of the crosslinking agent with respect to the total number A of carboxyl groups of the polymer. The ratio (B / A) of the total number B of one amino group is preferably 1/50 to 2/1. As a result, the crystallization of the drug can be more reliably prevented while enhancing the cohesiveness and adhesiveness of the adhesive layer 3, and the percutaneous absorption satisfying both the feeling of use and the transdermal absorbability of the drug at a higher level. The mold patch 1 can be realized. When (B / A) is less than 1/50, it tends to be difficult to ensure sufficient cohesiveness of the adhesive layer. When (B / A) exceeds 2/1, It tends to be difficult to ensure sufficient adhesiveness of the adhesive layer.

  In the present embodiment, the (B / A) is more preferably 1/50 to 1/1, and further preferably 1/50 to 1/5.

  In addition, as (B / A), a value (B1 × Mb / A1 × Ma) calculated by using the amine value B1 and the acid value A1 obtained by the following method may be substituted. In addition, Mb shows the compounding quantity (mass part) of a crosslinking agent, Ma shows the compounding quantity (mass part) of a polymer.

  In this specification, “amine value B1” indicates the total amount of 1, 2, and tertiary amines, and is expressed in mg of KOH equivalent to hydrochloric acid required to neutralize 1 g of a sample. Such a value can be determined according to the method described in ASTM D2074.

  In the present specification, “acid value A1” indicates the total amount of carboxyl groups, and is expressed in mg of KOH required to neutralize 1 g of a sample. Such a value can be determined according to the method described in JIS K 0070.

  Moreover, in this embodiment, when calculating | requiring the number of ester bonds of the crosslinking agent which has an ester bond in a molecule | numerator, it can calculate | require according to the method as described in JISK0070.

  The blending amount of the crosslinking agent is preferably in the range of 1 to 30% by mass, more preferably in the range of 1 to 20% by mass, based on the total amount of the adhesive layer 3. If the blending amount is less than 1% by mass, it tends to be difficult to obtain an excellent feeling of use of the patch and a high level of medicinal effect. It tends to decrease, and stringing of the adhesive layer is likely to occur at the time of peeling or a residue is likely to be generated.

  A non-functional adhesive base can be further blended in the adhesive base according to the present invention. Examples of the adhesive base include styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, polyisobutylene, polyisoprene, natural rubber, styrene-isoprene rubber, styrene-butadiene rubber, polydimethyl Well-known adhesive bases, such as siloxane, are mentioned. These additional adhesive bases are preferably blended at 50 mass% or less based on the total amount of the adhesive layer 3.

(Medicinal ingredients)
The medicinal component is not particularly limited, but a basic drug or a pharmaceutically acceptable salt of the basic drug is preferable in that it does not directly chemically react with the crosslinking agent.

  Examples of such drugs include hypnotic / sedatives (flurazepam hydrochloride, rilmazafone hydrochloride, etc.), antipyretic analgesics (butorphanol tartrate, perisoxal citrate, etc.), anti-migraine agents (ergotamine tartrate, ergotamine tartrate, etc.) (Methamphetamine hydrochloride, methylphenidate hydrochloride, etc.), neuropsychiatric agents (chlorpromazine hydrochloride, imipramine hydrochloride, etc.), local anesthetics (lidocaine hydrochloride, procaine hydrochloride, etc.), urinary organ agents (oxybutynin hydrochloride, etc.), skeletal muscle relaxants (Tizanidine hydrochloride, eperisone hydrochloride, pridinol mesylate, etc.), autonomic nerve agents (carpronium chloride, neostigmine bromide, etc.), antiparkinsonian agents (pergolide mesylate, bromocriptine mesylate, trihexyphenidyl hydrochloride, amantadine hydrochloride, etc.), Anti-histami Agents (clemastine fumarate, diphenhydramine tannate, etc.), bronchodilators (tulobuterol hydrochloride, procaterol hydrochloride, etc.), cardiotonic agents (isoprenalin hydrochloride, dopamine hydrochloride, etc.), coronary vasodilators (diltiazem hydrochloride, verapamil hydrochloride, etc.), peripheral vasodilators (Nicamethate citrate, trazoline hydrochloride, etc.), circulatory organ agents (flunarizine hydrochloride, nicardipine hydrochloride, benidipine hydrochloride, efonidipine hydrochloride, bisoprolol fumarate, timolol maleate, diltiazem hydrochloride, metoprolol tartrate), arrhythmic agent (propranolol hydrochloride) , Alprenolol hydrochloride, etc.), antiallergic agents (ketotifen fumarate, azelastine hydrochloride, etc.), antipruritic agents (betahistine mesylate, diphenidol hydrochloride, etc.), serotonin receptor antagonist antiemetics (ondanse hydrochloride) Ron, etc. granisetron hydrochloride), narcotic analgesics (morphine hydrochloride, fentanyl citrate, etc.). These drugs are appropriately selected according to the intended use of the transdermally absorbable preparation.

  The amount of the medicinal component is preferably in the range of 1 to 25% by mass, more preferably in the range of 5 to 15% by mass, based on the total amount of the adhesive layer 3. When the blending amount is less than 1% by mass, it tends to be difficult to obtain the effect of the medicinal component. On the other hand, when the blending amount exceeds 25% by mass, the adhesive strength and cohesiveness of the adhesive layer are lowered. There is a tendency.

(Other ingredients)
Examples of other components blended in the adhesive layer 3 include an absorption accelerator, a solubilizer, a tackifier, a plasticizer, a filler, and a stabilizer.

  As the absorption enhancer, any compound can be used as long as it is a compound known to promote absorption in the skin, for example, a fatty acid having 1 to 20 carbon chains or a salt thereof, an aliphatic alcohol, a fatty acid ester. Or ether, aromatic organic acid, aromatic alcohol, aromatic organic acid ester or ether (they may be saturated or unsaturated, and may be cyclic, linear or branched), lactic acid Examples include esters, acetate esters, terpenes, Azone, Azone derivatives, glycerin fatty acid esters, sorbitan fatty acid esters, polysorbates, polyethylene glycol fatty acid esters, polyoxyethylene hydrogenated castor oil, and sucrose fatty acid esters. It is done. Among these absorption enhancers, preferred examples include acetic acid, propionic acid, butyric acid, caprylic acid, capric acid, caproic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, Lauryl alcohol, myristyl alcohol, oleyl alcohol, cetyl alcohol, methyl laurate, isopropyl myristate, myristyl myristate, octyldodecyl myristate, cetyl palmitate, salicylic acid, methyl salicylate, ethylene glycol salicylate, cinnamic acid, methyl cinnamate , Cresol, cetyl lactate, ethyl acetate, propyl acetate, geraniol, thymol, eugenol, terpineol, l-menthol, borneolol, d-limonene, isoeugenol, isoborneol Nerol, dl-camphor, glycerol monolaurate, glycerol monooleate, sorbitan monolaurate, sucrose monolaurate, polysorbate 20, propylene glycol, polyethylene glycol monolaurate, polyethylene glycol monostearate, pyrothiodecane, etc. . Particularly preferred examples include lauryl alcohol, 1-menthol, propylene glycol, and pyrothiodecane. The absorption enhancer is appropriately blended according to the necessary transdermal absorption amount of the target drug.

  The solubilizer has an action of enhancing the absorbability of the drug by increasing the solubility of the drug in the pressure-sensitive adhesive layer 3. The solubilizer that can be used is not particularly limited, and a well-known solubilizer depending on the drug. It can be suitably selected from the agents. For example, the above absorption enhancer can be used as a drug solubilizer. In addition, since there exists a possibility that the cohesion force of the adhesion layer 3 may fall by mix | blending a solubilizer, it mix | blends suitably according to the solubility of the target drug in the range which does not impair the adhesion characteristic of the adhesion layer 3.

  A known resin can be used as the tackifier, and examples thereof include petroleum resins, terpene resins, and rosin resins. Examples of petroleum resins include aliphatic petroleum resins, aromatic petroleum resins, aliphatic-aromatic copolymer petroleum resins, and alicyclic petroleum resins. Examples of the terpene resin include β-pinene resin, α-pinene resin, hydrogenated terpene resin, and the like. Examples of the rosin resin include rosin glycerin ester and hydrogenated rosin glycerin ester. The blending amount of the tackifier is preferably 30% by mass or less based on the total amount of the adhesive layer 3 from the viewpoint of sufficiently ensuring the cohesiveness of the adhesive layer.

  The plasticizer can be used to control the adhesive properties of the adhesive layer 3, the flow properties of the coating liquid for forming the adhesive layer, and the drug absorbability. Usually, by blending a plasticizer, the cohesive force of the pressure-sensitive adhesive layer 3 is reduced, it has a flexible property, and the drug absorbability tends to increase somewhat. It does not specifically limit as a plasticizer, A well-known plasticizer or softener can be used. Specific examples include liquid paraffin, liquid polybutene, liquid polyisoprene, castor oil, cottonseed oil, palm oil, coconut oil, and the like. The blending amount of the plasticizer is preferably 30% by mass or less based on the total amount of the adhesive layer 3 from the viewpoint of sufficiently ensuring the cohesiveness of the adhesive layer.

  The filler can be used mainly for controlling the adhesive properties of the adhesive layer 3 and for concealing light rays. In addition, there exists a tendency for adhesive force to be suppressed by mix | blending a filler. It does not specifically limit as a filler, A well-known filler can be used. Specific examples include metal oxides such as zinc oxide and titanium oxide, metal hydroxides such as aluminum hydroxide, silicic acid compounds such as silicic acid and talc, and calcium carbonate. The blending amount of the filler is preferably 10% by mass or less based on the total amount of the adhesive layer 3 so that the filler does not inhibit the crosslinking of the adhesive layer.

  As the stabilizer, in order to enhance the stability of the adhesive layer 3 or the drug, a well-known antioxidant, ultraviolet absorber, or the like can be used. Specific examples of such a stabilizer include ascorbic acid derivatives, tocopherol derivatives, dibutylhydroxytoluene, edetate, 4-tert-butyl-4'-methoxydibenzoylmethane, and the like. The blending amount of the stabilizer is appropriately set according to the purpose of use of the transdermal absorption patch 1.

(Support)
The support 2 is a sheet-like substance that physically supports the adhesive layer 3 and protects the adhesive layer 3 from an external environment. Therefore, in order to handle the patch by hand or to apply it to the skin, it is necessary to have a physical support function, and the component in the adhesive layer 3 penetrates or breaks when the patch is peeled from the skin. Such is not preferred. As the support, a film, a fabric, a porous sheet, a paper-like material, or a laminate of these is used, and a film is most preferable. Examples of the material for the support include polyesters such as polyethylene terephthalate and polybutylene terephthalate, polyolefins such as polyethylene and polypropylene, and metal foils such as nylon, rayon, polyurethane, and aluminum. Of these, polyester is preferable in terms of flexibility according to the movement of the skin and difficulty in penetrating drugs.

(Peeling sheet)
The release sheet 4 is not particularly limited, and a known release sheet can be used. The release sheet 4 is coated and laminated on the adhesive layer 3 for protection during storage, and is peeled off when the transdermal absorption patch 1 is used. The release sheet is not particularly limited, such as a film, a paper-like one, or a laminate of these, but is most preferably a film. Specific examples of the material of the release sheet include polyesters such as polyethylene terephthalate, polybutylene terephthalate, and polyethylene naphthalate, polyolefins such as polyethylene and polypropylene, and metal foils such as nylon and aluminum. Of these, polyester is preferred from the viewpoint of temporal stability of the physical properties of the patch. The release sheet is preferably subjected to release treatment such as silicon treatment on the surface in order to facilitate peeling.

<Method for producing transdermal patch>
The transdermal patch 1 is prepared by, for example, applying a coating solution for forming an adhesive layer in which the adhesive base of the present embodiment, the medicinal component, and other components are dissolved or uniformly dispersed in a solvent. It can be manufactured by laminating the support 2 after uniformly coating on the release sheet 4 and removing the solvent of the coating film to form the adhesive layer 3.

  As the solvent, a known solvent can be used, and examples thereof include toluene, xylene, hexane, cyclohexane, ethyl acetate, propyl acetate and the like.

  The viscosity of the coating liquid for forming the adhesive layer is preferably in the range of 2000 to 6000 cps from the viewpoint of uniform spreadability during film formation.

  Moreover, the solid content concentration in the coating liquid for forming an adhesive layer is preferably in the range of 30 to 60% by mass in terms of uniform spreadability during film formation.

  As drying conditions for removing the solvent of a coating film, it is preferable to carry out at 60-100 degreeC for about 2 to 20 minutes. At this time, the crosslinking reaction between the polymer and the crosslinking agent also proceeds.

  Although the thickness of the adhesion layer 3 is suitably set according to the medicine to mix | blend, it is appropriate to set it as about 30-150 micrometers.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples.

Example 1
1.78 g (solid content: 0.8 g) of acrylic pressure-sensitive adhesive (trade name “Duro-Tak 87-2194”, manufactured by National Starch Co., Ltd., solid content: 45%), 0.2 g of fentanyl, 0.8 g of isopropyl myristate, Then, 0.2 g of a polyester / polyamine copolymer (Uniqema, trade name “Hypermer PS3”, base equivalent: 1100 to 1600, melting point: about 54 ° C.) dissolved in 0.4 g of ethyl acetate was added and stirred to be homogeneous A coating solution for forming an adhesive layer was prepared.

The coating solution obtained above is spread on the silicon-treated surface of a release sheet (polyethylene terephthalate film, thickness: 75 μm) so that the pressure-sensitive adhesive after drying is 50 g / m ^2, and dried to have a thickness of 50 μm. An adhesive layer was formed. Thereafter, a support (polyethylene terephthalate film, sand mat treatment, thickness: 25 μm) was laminated on the adhesive layer to obtain the transdermal absorption patch of Example 1. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Example 2)
Example 2 was the same as Example 1 except that the amount of the acrylic pressure-sensitive adhesive was 1.34 g (solid content: 0.6 g) and the amount of the polyester-polyamine copolymer “Hypermer PS3” was 0.4 g. A transdermal absorption patch was obtained. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Example 3)
The transdermal patch of Example 3 was used in the same manner as in Example 1 except that 0.2 g of polyester / polyamine copolymer “Hypermer KD-1” (Uniqema) was used instead of “Hypermer PS3”. Got. Table 1 shows the blending ratio of each component in the formed adhesive layer.

Example 4
The same procedure as in Example 3 was performed except that the blending amount of the acrylic pressure-sensitive adhesive was 1.34 g (solid content: 0.6 g) and the blending amount of the polyester / polyamine copolymer “Hypermer KD-1” was 0.4 g. The transdermal absorption patch of Example 4 was obtained. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Comparative Example 1)
The transdermal patch of Comparative Example 1 was obtained in the same manner as in Example 1 except that the polyester / polyamine copolymer was not blended and the blending amount of the acrylic pressure-sensitive adhesive was 2.22 g. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Comparative Example 2)
A transdermal absorption patch of Comparative Example 2 was obtained in the same manner as in Example 1 except that 0.2 g of ethylenediamine was added instead of the polyester / polyamine copolymer. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Comparative Example 3)
A transdermal absorption patch of Comparative Example 3 was obtained in the same manner as in Example 1 except that 0.2 g of dodecamethylenediamine was added instead of the polyester / polyamine copolymer. Table 1 shows the blending ratio of each component in the formed adhesive layer.

(Comparative Example 4)
A transdermal absorption patch of Comparative Example 4 was obtained in the same manner as in Example 1 except that 0.2 g of diethylenetriamine was added instead of the polyester / polyamine copolymer. Table 1 shows the blending ratio of each component in the formed adhesive layer.

  The cohesiveness, adhesiveness and storage stability of the patches obtained in Examples 1 to 4 and Comparative Examples 1 to 4 were evaluated based on the following evaluation criteria, and the probe tack value was measured according to the following method. did. The obtained results are summarized in Table 2.

<Evaluation of cohesiveness>
Each patch was cut into a circular test piece having a diameter of 25 mm, and then the separator was peeled off and the adhesive layer was attached to a bakelite plate. After 10 minutes, the state of the adhesive (adhesive layer) when the patch was peeled from the bakelite plate was observed and evaluated according to the following criteria.
A: No residue (adhesive) remaining. (Good)
B: The residue (adhesive) remainder is seen partially.
C: No residue (adhesive) remaining is observed, or when the patch is peeled off, adhesive threading is observed. (Bad)

<Evaluation of adhesiveness>
Each patch was cut into a circular test piece having a diameter of 25 mm, the separator was peeled off, and the adhesive layer was attached to a bakelite plate, and sensory evaluation was performed according to the following criteria.
A: Adhesiveness is suitable. (Good)
B: Although it has adhesiveness, it is easy to peel off.
C: Not sticky. (Bad)

<Storage stability>
The adhesive layer after each patch was stored at a temperature of 25 ° C. for 7 days and the adhesive layer after it was stored at a temperature of 25 ° C. for 1 month were visually observed to confirm the presence or absence of crystal precipitation. Table 2 shows the case where no crystal precipitation was observed as “no problem” and the case where crystal precipitation was observed as “crystal precipitation”.

<Probe tack value>
A patch of an appropriate size is applied to a ring load of 20 g, set on a probe tack tester in accordance with ASTM D-2979, and a stainless steel probe having a diameter of 5 mm is applied to the adhesive surface of the patch for 1 second at a speed of 5 mm / sec. The force (gf) required for pressing and peeling the probe at a speed of 5 mm / sec was measured.

  The patches obtained in Examples 1 to 4 and Comparative Examples 1, 2 and 4 were subjected to the following skin permeation test to evaluate the transdermal absorbability of the drug. In the skin permeation test, a patch that had undergone the above storage stability test (7 days and 1 month) was used.

<Skin penetration test>
The skin of the ventral side of the hairless mouse was peeled off, and the dermis side was set as the receptor tank side, and it was attached to a flow-through cell in which 37 ° C. warm water was circulated around the outer periphery. Next, a patch was applied to the stratum corneum side of the skin with an application area of 5 cm ² , and physiological saline was passed through the receptor tank at a flow rate of 10 ml / hour (hr), and sampling was performed every hour up to 12 hours. About the receptor solution obtained for every time, while measuring the flow volume, the drug concentration was measured using the high performance liquid chromatography. The drug permeation rate Flux (μg / cm ² / hr) per unit area of skin per hour was calculated from the obtained measured values. Graphs plotting the calculated values are shown in FIGS. Table 2 shows the maximum value of the drug permeation rate Flux (μg / cm ² / hr) per unit area of the skin. Further, graphs plotting cumulative drug permeation (μg / cm ² ) per unit area of skin are shown in FIGS. The cumulative drug permeation amount was calculated using the average value of drug permeation rates obtained by measuring multiple times.

  Note that the skin permeation test of the patch of Comparative Example 3 could not be performed because a part of the adhesive layer was peeled off when the patch separator was peeled off.

  As shown in Table 2, the patches of Examples 1 to 4 have moderate probe tack values, are sufficiently excellent in cohesiveness and adhesiveness, and are stored at 25 ° C. for 1 month. It was also confirmed that the drug has excellent transdermal absorbability. In addition, it was found that the patches of Examples 1 to 4 sufficiently prevented crystallization of the drug over time, and were sufficiently excellent in storage stability. In the patches of Examples 1 to 4, it is considered that a high drug permeation rate was stably obtained over a long period by sufficiently suppressing the crystallization of the drug.

  In addition, although “Duro-Tak 87-2194” used in the examples contains a metal chelate as a crosslinking agent, the patches of Examples 1 to 4 should contain the crosslinking agent according to the present invention. Thus, even in a system containing a metal chelate, the transdermal absorbability of the drug is increased to a sufficiently high level.

  On the other hand, it is also clear from Table 2 that the patch of Comparative Example 1 in which only a metal chelate is blended as a crosslinking agent cannot obtain a sufficient drug permeation rate. Further, in the patches of Comparative Example 2 in which ethylenediamine was blended as a cross-linking agent and Comparative Example 4 in which diethylenetriamine was blended, drug crystals precipitated over time. In addition, it was confirmed that the patches of Comparative Examples 2 and 4 after being stored at 25 ° C. for 1 month have a low drug permeation rate and are insufficient to obtain an excellent medicinal effect. The drug permeation rate of the patch of Comparative Example 2 after storage at 25 ° C. for 7 days was high in the initial value of the measurement, but after 4 hours, the drug permeation rate was lower than that of Comparative Example 1, and excellent drug efficacy. It was confirmed that it was insufficient to obtain This is because although the drug dissolved in the adhesive layer was released, a high drug permeation rate was initially obtained, but when it was consumed, the rate at which the crystallized drug dissolved in the adhesive layer was rate-limiting and permeated. This is thought to be the result of a decrease in speed.

  As described above, the adhesive base and the transdermal absorption patch of the present invention are particularly useful in the field of the pharmaceutical industry for the purpose of preventing or treating diseases.

Claims (9)

Acrylic acid or methacrylic acid include a copolymer comprising a monomer component, a crosslinking agent for crosslinking the copolymer, and
The cross-linking agent is selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule containing two or more ester bonds and / or ether bonds in the molecule in total. Ri compounds der comprising at least one of the two or more amino groups in total is,
The adhesive base whose said crosslinking agent is a polyester / polyamine copolymer or a polyether / polyamine copolymer .   The pressure-sensitive adhesive base according to claim 1, wherein the crosslinking agent is a compound having a polyester structural unit having 2 to 100 ester bonds in the molecule.   The cross-linking agent is a compound containing a total of four or more at least one amino group selected from the group consisting of a primary amino group, a secondary amino group, and a tertiary amino group in the molecule. Item 3. The adhesive base according to Item 1 or 2. The pressure-sensitive adhesive base according to any one of claims 1 to 3 , wherein the crosslinking agent has a weight average molecular weight of 2000 to 20000. The total number B of at least one amino group selected from the group consisting of a primary amino group, a secondary amino group and a tertiary amino group of the crosslinking agent with respect to the total number A of carboxyl groups of the polymer. The pressure-sensitive adhesive base according to any one of claims 1 to 4 , wherein the ratio (B / A) is 1/50 to 2/1. Comprising the copolymer as (meth) acrylic acid ester copolymer, adhesive base agent according to any one of claims 1-5. A percutaneous absorption comprising: a support; and an adhesive layer provided on at least one surface of the support and comprising the adhesive base according to any one of claims 1 to 6 and a medicinal component. Mold patch. The transdermal patch according to claim 7 , wherein the medicinal component comprises a basic drug and / or a pharmaceutically acceptable salt of the basic drug. The transdermal patch according to claim 7 or 8 , wherein the amount of the crosslinking agent is 1 to 30% by mass based on the total amount of the adhesive layer.

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