ADHESIVE PATCH

Abstract

An object is to provide an adhesive patch that is excellent in both percutaneous absorbability of a drug and adhesiveness to the skin. An adhesive patch of the present invention includes a backing and an adhesive layer integrally laminated on one side of the backing, the adhesive layer including a drug, levulinic acid, and an acrylic adhesive including an acrylic polymer (A) containing a vinyl-based monomer (I) moiety having a solubility parameter of 9 (cal/cm.sup.3).sup.1/2 or more. According to the present invention, it is possible to provide an adhesive patch that is excellent in both percutaneous absorbability of a drug and adhesiveness to the skin.

Claims

1. An adhesive patch comprising: a backing; and an adhesive layer integrally laminated on one side of the backing, the adhesive layer including a drug, levulinic acid, and an acrylic adhesive including an acrylic polymer (A) containing a vinyl-based monomer (I) moiety having a solubility parameter of 9 (cal/cm.sup.3).sup.2 or more.

2. The adhesive patch according to claim 1, wherein the drug includes an amine structure in a molecular structure.

3. The adhesive patch according to claim 1, wherein the drug includes at least one selected from the group consisting of blonanserin, buprenorphine, rotigotine, and guanfacine.

4. The adhesive patch according to claim 1, wherein a mass ratio of levulinic acid to the drug [(mass of levulinic acid)/(mass of drug)] is 0.2 or more and 4 or less.

5. The adhesive patch according to claim 1, wherein the vinyl-based monomer (I) moiety contains at least one selected from the group consisting of an N-vinyl-2-pyrrolidone moiety, a diacetone acrylamide moiety, a methyl acrylate moiety, and a 2-hydroxyethyl acrylate moiety.

6. The adhesive patch according to claim 1, wherein the acrylic polymer (A) contains a vinyl-based monomer (II) moiety having a solubility parameter of less than 9 (cal/cm.sup.3).sup.1/2.

7. The adhesive patch according to claim 6, wherein the vinyl-based monomer (II) moiety contains an alkyl (meth)acrylate moiety having an alkyl group having 1 to 16 carbon atoms.

8. The adhesive patch according to claim 6, wherein the vinyl-based monomer (II) moiety contains at least one selected from the group consisting of an ethyl acrylate moiety, a 2-ethylhexyl acrylate moiety, a 2-ethylhexyl methacrylate moiety, an n-octyl acrylate moiety, and a dodecyl methacrylate moiety.

9. The adhesive patch according to claim 6, wherein: the drug includes at least one selected from the group consisting of blonanserin, buprenorphine, rotigotine, and guanfacine; the vinyl-based monomer (I) moiety contains at least one selected from the group consisting of an N-vinyl-2-pyrrolidone moiety, a diacetone acrylamide moiety, a methyl acrylate moiety, a 2-hydroxyethyl acrylate moiety, and an acrylic acid moiety; and the vinyl-based monomer (II) moiety contains at least one selected from the group consisting of an ethyl acrylate moiety, a 2-ethylhexyl acrylate moiety, a 2-ethylhexyl methacrylate moiety, an n-octyl acrylate moiety, and a dodecyl methacrylate moiety.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0125] FIG. 1 is a graph schematically showing a relationship between a moving distance of a cylindrical probe and a load in probe tack testing.

DESCRIPTION OF EMBODIMENTS

[0126] The present invention will be described in more detail below using examples. However, the present invention is not limited to these examples.

EXAMPLES

[0127] (Preparation of Acrylic Polymer (A1))

[0128] A reaction liquid containing monomers including 75 parts by mass of 2-ethylhexyl acrylate and 25 parts by mass of N-vinyl-2-pyrrolidone, and 50 parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 1.2 parts by mass of lauroyl peroxide in 30 parts by mass of ethyl acetate and 20 parts by mass of cyclohexane was added to the above-mentioned reaction liquid over 24 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A1) solution containing 30% by mass of the acrylic polymer (A1).

[0129] (Preparation of Acrylic Polymer (A2))

[0130] A reaction liquid containing monomers including 40 parts by mass of n-octyl acrylate, 50 parts by mass of ethyl acrylate, and 10 parts by mass of N-vinyl-2-pyrrolidone, and parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 1 part by mass of lauroyl peroxide in 30 parts by mass of ethyl acetate and 20 parts by mass of cyclohexane was added to the above-mentioned reaction liquid over 24 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A2) solution containing 30% by mass of the acrylic polymer (A2).

[0131] (Preparation of Acrylic Polymer (A3))

[0132] A reaction liquid containing monomers including 13 parts by mass of dodecyl methacrylate, 78 parts by mass of 2-ethylhexyl methacrylate, and 9 parts by mass of 2-ethylhexyl acrylate, and 50 parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 0.5 parts by mass of benzoyl peroxide in 10 parts by mass of ethyl acetate and 10 parts by mass of cyclohexane was added to the above-mentioned reaction liquid over 24 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A3) solution containing 30% by mass of the acrylic polymer (A3).

[0133] (Preparation of Acrylic Polymer (A4))

[0134] A reaction liquid containing monomers including 71 parts by mass of 2-ethylhexyl acrylate, 24 parts by mass of methyl acrylate, and 5 parts by mass of 2-hydroxyethyl acrylate, and parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 0.5 parts by mass of benzoyl peroxide in 10 parts by mass of n-hexane was added to the above-mentioned reaction liquid over 24 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A4) solution containing 40% by mass of the acrylic polymer (A4).

[0135] (Preparation of Acrylic Polymer (A5))

[0136] A reaction liquid containing monomers including 50 parts by mass of n-octyl acrylate, 45 parts by mass of ethyl acrylate, and 5 parts by mass of N-vinyl-2-pyrrolidone, and 140 parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 0.4 parts by mass of lauroyl peroxide in 20 parts by mass of ethyl acetate was added to the above-mentioned reaction liquid over 14 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A5) solution containing 30% by mass of the acrylic polymer (A5).

[0137] (Preparation of Acrylic Polymer (A6))

[0138] A reaction liquid containing monomers including 65 parts by mass of 2-ethylhexyl acrylate and 35 parts by mass of N-vinyl-2-pyrrolidone, and 185 parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 0.6 parts by mass of lauroyl peroxide in 17 parts by mass of ethyl acetate was added to the above-mentioned reaction liquid over 14 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A6) solution containing 30% by mass of the acrylic polymer (A6).

[0139] (Preparation of Acrylic Polymer (A7))

[0140] A reaction liquid containing monomers including 75 parts by mass of 2-ethylhexyl acrylate, 3 parts by mass of acrylic acid, and 22 parts by mass of N-vinyl-2-pyrrolidone, and 150 parts by mass of ethyl acetate was supplied to a polymerizer, and the inside of the polymerizer was brought to a nitrogen atmosphere at 80° C. Then, a polymerization initiator solution obtained by dissolving 0.6 parts by mass of lauroyl peroxide in 17 parts by mass of ethyl acetate was added to the above-mentioned reaction liquid over 14 hours to copolymerize the above-mentioned monomers. After the polymerization was completed, ethyl acetate was further added to the above-mentioned reaction liquid to obtain an acrylic polymer (A7) solution containing 30% by mass of the acrylic polymer (A7).

[0141] Solubility parameters of the monomers used for preparing the acrylic polymers (A1) to (A7) are shown in Table 1.

TABLE-US-00001 TABLE 1 Solubility parameter (cal/cm.sup.3).sup.1/2 Ethyl acrylate 8.8 2-Ethylhexyl acrylate 7.8 2-Ethylhexyl methacryate 8.3 n-Octyl acrylate 8.2 Dodecyl methacrylate 8.2 Methyl acrylate 9.4 2-Hydroxyethyl acrylate 12.1 N-Vinyl-2-pyrrolidone 9.7 Acrylic acid 11.7

Example 1

[0142] A free base form blonanserin, levulinic acid, and the acrylic polymer (A1) solution were mixed such that the free base form blonanserin, levulinic acid, and the acrylic polymer (A1) were each comprised in an adhesive layer in a blending amount shown in Table 2, thereby producing an adhesive layer-forming solution. Next, a polyethylene terephthalate film having a thickness of 38 μm and subjected to a silicone release treatment was prepared as a release liner. The adhesive layer-forming solution was applied onto the silicone release-treated side of this polyethylene terephthalate film and dried at 60° C. for 30 minutes, thereby producing a laminate with an 80 μm-thick adhesive layer formed on the silicone release-treated side of the polyethylene terephthalate film. Then, a polyethylene terephthalate film with a thickness of 25 μm was prepared as a backing, and one side of the backing and the adhesive layer of the above-mentioned laminate were laminated so as to face each other, so that the adhesive layer of the laminate was transferred to and integrally laminated on the backing, thereby producing an adhesive patch. The gel fraction of the adhesive layer is shown in Table 2.

[0143] Note that 0.1 g or more of the free base form blonanserin could be dissolved in 1 mL of levulinic acid at a liquid temperature of 35° C.

Example 2

[0144] An adhesive patch was produced in the same manner as in Example 1 except that the free base form blonanserin, levulinic acid, and the acrylic polymer (A2) solution were mixed such that the free base form blonanserin, levulinic acid, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 2, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 2.

Example 3

[0145] An adhesive patch was produced in the same manner as in Example 1 except that the free base form blonanserin, levulinic acid, and the acrylic polymer (A4) solution were mixed such that the free base form blonanserin, levulinic acid, and the acrylic polymer (A4) were each comprised in the adhesive layer in a blending amount shown in Table 2, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 2.

Comparative Example 1

[0146] An adhesive patch was produced in the same manner as in Example 1 except that the free base form blonanserin, isopropyl myristate, and the acrylic polymer (A2) solution were mixed such that the free base form blonanserin, isopropyl myristate, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 2, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 2.

Comparative Example 2

[0147] An adhesive patch was produced in the same manner as in Example 1 except that the free base form blonanserin, levulinic acid, and the acrylic polymer (A3) solution were mixed such that the free base form blonanserin, levulinic acid, and the acrylic polymer (A3) were each comprised in the adhesive layer in a blending amount shown in Table 2, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 2. However, in the adhesive patch of Comparative example 2, a liquid component, which was considered to be levulinic acid, was leaked excessively to the surface of the adhesive layer immediately after production, resulting in a decrease in the adhesiveness of the adhesive layer. Thus, the adhesive patch of Comparative example 2 was not evaluated for the percutaneous absorbability described below.

Example 4

[0148] A free base form guanfacine, levulinic acid, isopropyl myristate, and the acrylic polymer (A2) solution were mixed such that the free base form guanfacine, levulinic acid, isopropyl myristate, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 3, thereby producing an adhesive layer-forming solution. Next, a polyethylene terephthalate film having a thickness of μm and subjected to a silicone release treatment was prepared as a release liner. The adhesive layer-forming solution was applied onto the silicone release-treated side of this polyethylene terephthalate film and dried at 60° C. for 30 minutes, thereby producing a laminate with a 70 μm-thick adhesive layer formed on the silicone release-treated side of the polyethylene terephthalate film. Then, a polyethylene terephthalate film with a thickness of 38 μm was prepared as a backing, and one side of the backing and the adhesive layer of the above-mentioned laminate were laminated so as to face each other, so that the adhesive layer of the laminate was transferred to and integrally laminated on the backing, thereby producing an adhesive patch. The gel fraction of the adhesive layer is shown in Table 3.

[0149] Note that 0.1 g or more of the free base form guanfacine could be dissolved in 1 mL of levulinic acid at a liquid temperature of 35° C.

Comparative Example 3

[0150] An adhesive patch was produced in the same manner as in Example 4 except that the free base form guanfacine, isopropyl myristate, and the acrylic polymer (A2) solution were mixed such that the free base form guanfacine, isopropyl myristate, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 3, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 3.

[0151] Note that in Table 3, the blending amount of each of the free base form guanfacine, levulinic acid, isopropyl myristate, and the acrylic polymer (A2) in the adhesive layer is indicated by a numerical value not enclosed in parentheses. Furthermore, the content ratio of each of the free base form guanfacine, levulinic acid, and the acrylic polymer (A2) in the adhesive layer in 100 parts by mass of the total amount of the free base form guanfacine, levulinic acid, and the acrylic polymer (A2) is indicated by a numerical value enclosed in parentheses in the column of each component in Table 3. Furthermore, the content of isopropyl myristate in the adhesive layer relative to 100 parts by mass of the acrylic polymer (A2) is indicated by a numerical value enclosed in parentheses in the column of “Isopropyl myristate” in Table 3.

Example 5

[0152] A free base form rotigotine, levulinic acid, isopropyl myristate, and the acrylic polymer (A2) solution were mixed such that the free base form rotigotine, levulinic acid, isopropyl myristate, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 4, thereby producing an adhesive layer-forming solution. Next, a polyethylene terephthalate film having a thickness of 38 μm and subjected to a silicone release treatment was prepared as a release liner. The adhesive layer-forming solution was applied onto the silicone release-treated side of this polyethylene terephthalate film and dried at 60° C. for 30 minutes, thereby producing a laminate with a 45 μm-thick adhesive layer formed on the silicone release-treated side of the polyethylene terephthalate film. Then, a polyethylene terephthalate film with a thickness of 25 μm was prepared as a backing, and one side of the backing and the adhesive layer of the above-mentioned laminate were laminated so as to face each other, so that the adhesive layer of the laminate was transferred to and integrally laminated on the backing, thereby producing an adhesive patch. The gel fraction of the adhesive layer is shown in Table 4.

[0153] Note that 0.1 g or more of the free base form rotigotine could be dissolved in 1 mL of levulinic acid at a liquid temperature of 35° C.

Comparative Example 4

[0154] An adhesive patch was produced in the same manner as in Example 5 except that the free base form rotigotine, isopropyl myristate, and the acrylic polymer (A2) solution were mixed such that the free base form rotigotine, isopropyl myristate, and the acrylic polymer (A2) were each comprised in the adhesive layer in a blending amount shown in Table 4, thereby producing an adhesive layer-forming solution. The gel fraction of the adhesive layer is shown in Table 4.

Comparative Example 5

[0155] An adhesive patch was produced in the same manner as in Example 5 except that the free base form rotigotine, levulinic acid, isopropyl myristate, and the acrylic polymer (A3) solution were mixed such that the free base form rotigotine, levulinic acid, isopropyl myristate, and the acrylic polymer (A3) were each comprised in the adhesive layer in a blending amount shown in Table 4, thereby producing an adhesive layer-forming solution. However, in the adhesive patch of Comparative example 5, a liquid component, which was considered to be levulinic acid, was leaked excessively to the surface of the adhesive layer immediately after production, resulting in a decrease in the adhesiveness of the adhesive layer. Thus, the adhesive patch of Comparative example 5 was not evaluated for the percutaneous absorbability described below. The gel fraction of the adhesive layer is shown in Table 4.

Examples 6 to 16 and Comparative Examples 6 to 8

[0156] Adhesive patches were produced in the same manner as in Example 5 except that the free base form rotigotine, levulinic acid, isopropyl myristate, the acrylic polymer (A1) solution to the acrylic polymer (A3) solution, and the acrylic polymer (A5) solution to the acrylic polymer (A7) solution were mixed such that the free base form rotigotine, levulinic acid, isopropyl myristate, the acrylic polymer (A1) to the acrylic polymer (A3), and the acrylic polymer (A5) to the acrylic polymer (A7) were each comprised in the adhesive layers in a blending amount shown in Table 4, thereby producing adhesive layer-forming solutions. The gel fraction of the adhesive layers is shown in Table 4.

[0157] Note that in Table 4, the blending amount of each of the free base form rotigotine, levulinic acid, isopropyl myristate, and the acrylic polymer (A) in the adhesive layer is indicated by a numerical value not enclosed in parentheses. Furthermore, the content ratio of each of the free base form rotigotine, levulinic acid, and the acrylic polymer (A) in the adhesive layer in 100 parts by mass of the total amount of the free base form rotigotine, levulinic acid, and the acrylic polymer (A) is indicated by a numerical value enclosed in parentheses in the column of each component in Table 4. Furthermore, the content of isopropyl myristate in the adhesive layer relative to 100 parts by mass of the acrylic polymer (A) is indicated by a numerical value enclosed in parentheses in the column of “isopropyl myristate” in Table 4.

[0158] (Performance Evaluation of Adhesive Patch)

[0159] The adhesive patches of Examples and Comparative examples were evaluated for the percutaneous absorbability according to the following procedure. Furthermore, the adhesive patches of Examples and Comparative examples were evaluated for the adhesiveness according to the following procedure.

[0160] (Percutaneous Absorbability)

[0161] Five flat square test pieces, each with an area of 3 cm.sup.2, were punched out from the adhesive patch. The adhesive layer of each of the three test pieces was dissolved in a solvent, and the amount of the drug was measured using HPLC (high-performance liquid chromatography). The arithmetic mean value of these measurements was calculated as a “pre-test drug amount (μg/cm.sup.2)”. The release liner was peeled off from each of the remaining two test pieces to expose the entire adhesive layer. Then, each test piece was stuck to the back of a Wistar rat (7 weeks old), whose back was shaved, for 24 hours. After removing the test piece from the back of the rat, each adhesive layer was dissolved in a solvent, and the amount of the drug was measured using HPLC. The arithmetic mean value of these measurements was calculated as a “post-test drug amount (μg/cm.sup.2)”. A value obtained by subtracting the “post-test drug amount” from the “pre-test drug amount” was defined as a “percutaneous absorption amount (μg/cm.sup.2)” and shown in Tables 2 to 4.

[0162] As the solvent for dissolving the adhesive layer in the measurement of the drug amount using HPLC, tetrahydrofuran was used in a case where the drug included in the adhesive layer was the free base form blonanserin or the free base form rotigotine, while dimethylformamide was used in a case where the drug included in the adhesive layer was the free base form guanfacine.

[0163] (Adhesiveness Test)

[0164] A test piece (1.7 mm height×1.7 mm width) was cut out from the adhesive patch. The release liner was peeled off and removed from the test piece to expose the adhesive layer, and the test piece was placed on a horizontal surface with the adhesive layer facing up. A cylindrical probe was brought into contact with the surface of the adhesive layer according to “3.4. Probe tack testing” of General Tests “6.13 Methods of Adhesion Testing” of the Japanese Pharmacopoeia, 17th Edition. Then, the cylindrical probe was peeled off while being moved vertically from the surface of the adhesive layer, and the resistance force received by the cylindrical probe due to the adhesive force of the surface of the adhesive layer when peeling off was measured as a load (N/cm.sup.2). Note that the load measurement was performed multiple times while changing the measurement interval for each moving distance of the cylindrical probe in contact with the adhesive layer surface.

[0165] Specifically, the load was measured each time the cylindrical probe moved by 0.01 mm until the moving distance of the cylindrical probe in contact with the adhesive layer surface reached 0.12 mm (number of measurements n: 1st to 12th). The load was measured each time the cylindrical probe moved by 0.02 mm until the moving distance of the cylindrical probe exceeded 0.12 mm and reached 0.48 mm (number of measurements n: 13th to 30th). The load was measured each time the cylindrical probe moved by 0.03 mm until the moving distance of the cylindrical probe exceeded 0.48 mm and reached 1.02 mm (number of measurements n: 31st to 48th). The load was measured each time the cylindrical probe moved by 0.04 mm until the moving distance of the cylindrical probe exceeded 1.02 mm and reached 1.98 mm (number of measurements n: 49th to 72nd). After that, the load was measured each time the cylindrical probe moved by 0.05 mm (number of measurements n: 73rd and thereafter). Then, the maximum load (N/cm.sup.2) and the load area [(N/cm.sup.2)×mm] required to peel off the cylindrical probe are shown in Tables 2 to 4.

[0166] Note that the load area was calculated on the basis of the following formula (1) where Ln (N/cm.sup.2) represented the load measured at the n-th time in the load measured until the moving distance of the cylindrical probe in contact with the adhesive layer surface reached 27 mm. Note that the load area is described below. First, the measured values of the load measured as described above were plotted on a graph with the X-axis representing the moving distance (mm) of the cylindrical probe and the Y-axis representing the load (N/cm.sup.2), thereby drawing a curve. A schematic diagram of the above-mentioned graph is shown in FIG. 1. In the above-mentioned graph, the load area is represented by a value approximated to the area of a part (shaded part in FIG. 1) surrounded by the above-mentioned curve, the X axis, and a straight line L that passes through the point on the X axis at X=27 mm and is parallel to the Y axis. That is, the load area corresponds to an integrated value of the load until the moving distance of the cylindrical probe in contact with the adhesive layer surface reaches 27 mm.

[00001]$\left[\mathrm{Mathematical}\mathrm{formula}1\right]$$\begin{array}{cc}\mathrm{Load}\mathrm{Area}\left[\left(N/{\mathrm{cm}}^2\right)\times \mathrm{mm}\right]=\underset{n=1}{\overset{12}{.Math.}}\left[\frac{\left(L_n+L_{n-1}\right)}{2}\right]\times 0.01+\underset{n=13}{\overset{30}{.Math.}}\left[\frac{(L_n+L_{n-1}}{2}\right]\times 0.02+\underset{n=31}{\overset{48}{.Math.}}\left[\frac{\left(L_n+L_{n-1}\right)}{2}\right]\times 0.03+\underset{n=49}{\overset{72}{.Math.}}\left[\frac{\left(L_n+L_{n-1}\right)}{2}\right]\times 0.04+\underset{n=73}{\overset{574}{.Math.}}\left[\frac{\left(L_n+L_{n-1}\right)}{2}\right]\times 0.05& \left(1\right)\end{array}$

[0167] The maximum load in the probe tack testing is preferably 23 N/cm.sup.2 or more. The maximum load of 23 N/cm.sup.2 or more means that the adhesive layer exhibits excellent adhesiveness, allowing for reduction of peeling of the adhesive patch from the skin during application and stably stick the adhesive patch to the skin. Note that if the maximum load is too high, the skin may be damaged when the adhesive patch is removed from the skin. Thus, the maximum load in the probe tack testing is preferably 100 N/cm.sup.2 or less.

[0168] Furthermore, the load area in the probe tack testing is preferably 20 (N/cm.sup.2)×mm or more. The load area of 20 (N/cm.sup.2)×mm or more means that the adhesive layer exhibits further excellent adhesiveness, allowing for further reduction of the adhesive patch peeling off of the skin during application and further stability in the adhesive patch sticking to the skin. Note that if the load area is too high, the skin may be damaged when the adhesive patch is removed from the skin. Thus, the load area in the probe tack testing is preferably 120 (N/cm.sup.2)×mm or less.

TABLE-US-00002 TABLE 2 Comparative Comparative Example 1 Example 2 Example 3 Example 1 Example 2 Adhesive layer Free base form blonanserin 6.5 6.5 6.5 6.5 6.5 composition Levulinic acid 10 10 10 0 10 [Parts by mass] Isopropyl myristate 0 0 0 10 0 Acrylic polymer (A1) 83.5 0 0 0 0 Acrylic polymer (A2) 0 83.5 0 83.5 0 Acrylic polymer (A3) 0 0 0 0 83.5 Acrylic polymer (A4) 0 0 83.5 0 0 Mass ratio [(mass of levulinic acid)/(mass of drug)] 1.5 1.5 1.5 — 1.5 Gel fraction of adhesive layer [% by mass] 1 or less 1 or less 1 or less 1 or less 1 or less Percutaneous absorption amount [μg/cm.sup.2] 102 98 102 46 — Probe tack testing maximum load [N/cm.sup.2] 74 57 40 50 19 Probe tack testing load area [(N/cm.sup.2) × mm] 94 80 48 57 8

TABLE-US-00003 TABLE 3 Comparative Example 4 example 3 Adhesive Free base form 5 (5.6) 5 (5.6) layer guanfacine composition Levulinic 2.6 (2.9) 0 (0) [Parts by acid mass] Isopropyl myristate 10 (12.1) 10 (11.8) Acrylic polymer (A2) 82.4 (91.5) 85 (94.4) Mass ratio [(mass of 0.5 — levulinic acid)/(mass of drug)] Gel fraction of adhesive layer 1 or less 1 or less [% by mass] Percutaneous absorption amount 38 0 [(μg/cm.sup.2] Probe tack testing maximum load 39 36 [N/cm.sup.2] Probe tack testing load area 37 28 [(N/cm.sup.2)xmm]

TABLE-US-00004 TABLE 4 Exam- Exam- Exam- Exam- Exam- Exam- Exam- Exam- Exam- Exam- ple 5 ple 6 ple 7 ple 8 ple 9 ple 10 ple 11 ple 12 ple 13 ple 14 Adhesive layer Free base form 10 25 25 25 25 25 20 25 25 25 composition rotigotine (13.2) (28.4) (28.4) (28.4) (28.4) (28.4) (22.7) (28.4) (28.4) (25.0) [Parts by Levulinic acid 10 10 10 10 10 10 8 5 15 10 mass] (13.2) (11.4) (11.4) (11.4) (11.4) (11.4) (9.1) (5.7) (17.1) (10.0) Isopropyl myristate 24 12 12 12 12 12 12 12 12 0 (42.9) (22.6) (22.6) (22.6) (22.6) (22.6) (20.0) (20.7) (25.0) (0) Acrylic polymer (A2) 56 53 0 0 0 0 60 58 48 65 (73.6) (60.2) (0) (0) (0) (0) (68.2) (65.9) (54.5) (65.0) Acrylic polymer (A5) 0 0 53 0 0 0 0 0 0 0 (0) (0) (60.2) (0) (0) (0) (0) (0) (0) (0) Acrylic polymer (A1) 0 0 0 53 0 0 0 0 0 0 (0) (0) (0) (60.2) (0) (0) (0) (0) (0) (0) Acrylic polymer (A6) 0 0 0 0 53 0 0 0 0 0 (0) (0) (0) (0) (60.2) (0) (0) (0) (0) (0) Acrylic polymer (A7) 0 0 0 0 0 53 0 0 0 0 (0) (0) (0) (0) (0) (60.2) (0) (0) (0) (0) Acrylic polymer (A3) 0 0 0 0 0 0 0 0 0 0 (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) Mass ratio [(mass of levulinic acid)/   1.0   0.4   0.4   0.4 0.4   0.4   0.4   0.2   0.6   0.4   (mass of drug)] Gel fraction of adhesive layer 1 or 1 or 1 or 1 or 1 or 1 or 1 or 1 or 1 or 1 or [% by mass] less less less less less less less less less less Percutaneous absorption amout 152  250  203  163  160  149  182  191  219  155  [μg/cm.sup.2] Probe tack testing maximum load 25 33 36 38 34 39 37 36 33 40 [N/cm.sup.2] Probe tack testing load area 32 25 24 28 22 26 27 27 23 27 [N/cm.sup.2) × mm] Compar- Compar- Compar- Compar- Compar- Exam- Exam- ative ative ative ative ative ple 15 ple 16 example 4 example 5 example 6 example 7 example 8 Adhesive layer Free base form 25 30 10 10 25 25 25 composition rotigotine (26.0) (34.1) (13.2) (13.2) (28.4) (28.4) (28.4) [Parts by Levulinic acid 10 12 0 10 0 0 0 mass] (10.5) (13.6) (0) (13.2) (0) (0) (0) Isopropyl myristate 4 12 24 24 12 12 12 (6.6) (26.1) (36.4) (42.9) (19.0) (19.0) (19.0) Acrylic polymer (A2) 61 46 66 0 63 0 0 (63.5) (52.3) (86.8) (0) (71.6) (0) (0) Acrylic polymer (A5) 0 0 0 0 0 0 0 (0) (0) (0) (0) (0) (0) (0) Acrylic polymer (A1) 0 0 0 0 0 63 0 (0) (0) (0) (0) (0) (71.6) (0) Acrylic polymer (A6) 0 0 0 0 0 0 0 (0) (0) (0) (0) (0) (0) (0) Acrylic polymer (A7) 0 0 0 0 0 0 63 (0) (0) (0) (0) (0) (0) (71.6) Acrylic polymer (A3) 0 0 0 56 0 0 0 (0) (0) (0) (73.6) (0) (0) (0) Mass ratio [(mass of levulinic acid)/   0.4   0.4 —   1.0 — — — (mass of drug)] Gel fraction of adhesive layer 1 or 1 or 1 or 1 or 1 or 1 or 1 or [% by mass] less less less less less less less Percutaneous absorption amout 238  253  114  — 112  59 53 [μg/cm.sup.2] Probe tack testing maximum load 42 37 34 20 23 32 22 [N/cm.sup.2] Probe tack testing load area 31 28 36 17 14 20 12 [N/cm.sup.2) × mm]

INDUSTRIAL APPLICABILITY

[0169] According to the present invention, it is possible to provide an adhesive patch that is excellent in both percutaneous absorbability of a drug and adhesiveness to the skin.

CROSS-REFERENCE TO RELATED APPLICATION

[0170] The present application claims the priority under Japanese Patent Application No. 2020-138958, filed on Aug. 19, 2020, the disclosure of which is hereby incorporated in its entirety by reference.