ADHESIVE PATCH

Abstract

Provided is an adhesive patch capable of exerting excellent tackiness when the adhesive patch is attached to the skin and having a low incidence of detachment from the skin during attachment. The adhesive patch of the present invention includes a support, and an adhesive layer integrally layered on one surface of the support, the adhesive layer containing an acrylic adhesive, a solid resin that is incompatible with the acrylic adhesive and is in a solid state at 40 C., a plasticizer, and a drug. The combined use of the solid resin and the plasticizer can simultaneously achieve the tackiness and cohesive force of the adhesive layer.

Claims

1-9. (canceled)

10. An adhesive patch comprising: a support; and an adhesive layer integrally layered on one surface of the support, the adhesive layer containing 100 parts by weight of an acrylic adhesive, 1 to 25 parts by weight of a solid resin that is incompatible with the acrylic adhesive and is in a solid state at 40 C., the solid resin containing at least one kind of resin selected from the group consisting of ethyl cellulose, a styrene-isoprene-styrene block copolymer, and a terpene resin, 5 to 80 parts by weight of a plasticizer containing at least one kind selected from the group consisting of octyldodecanol, isopropyl myristate, and a liquid paraffin, and 1 to 40 parts by weight of a liquid drug being in a liquid state at 30 C. and containing at least one kind of the liquid drug having a plasticization effect selected from the group consisting of rivastigmine, selegiline, and ethyl salicylate; wherein a ratio by weight of a total amount of the plasticizer (P.sub.1) and the liquid drug having a plasticization effect (P.sub.2) to an amount of the solid resin (S) [(P.sub.1+P.sub.2)/S] is 1.5 to 25.

11. The adhesive patch according to claim 10, wherein a difference between a solubility parameter of the acrylic adhesive and a solubility parameter of the solid resin is 0.5 (cal/cm.sup.3).sup.1/2 or more.

12. The adhesive patch according to claim 10, wherein the solid resin consists of at least one kind of resin selected from the group consisting of ethyl cellulose, a styrene-isoprene-styrene block copolymer, and a terpene resin.

13. The adhesive patch according to claim 10, wherein the plasticizer consists of at least one kind selected from the group consisting of octyldodecanol, isopropyl myristate, and a liquid paraffin.

14. The adhesive patch according to claim 10, wherein the liquid drug consists of rivastigmine.

15. The adhesive patch according to claim 10, wherein a ratio by weight of a total amount of the plasticizer (P.sub.1) and the liquid drug having a plasticization effect (P.sub.2) to an amount of the solid resin (S) [(P.sub.1+P.sub.2)/S] is 2.5 to 25.

16. The adhesive patch according to claim 10, wherein the acrylic adhesive contains a copolymer of dodecyl methacrylate, 2-ethyl hexyl acrylate, and 2-ethythexyl methacrylate.

17. The adhesive patch according to claim 11, wherein the solid resin consists of at least one kind of resin selected from the group consisting of ethyl cellulose, a styrene-isoprene-styrene block copolymer, and a terpene resin.

Description

DESCRIPTION OF EMBODIMENTS

[0068] Hereinafter, the present invention will be described more specifically by Examples, but the invention is not limited thereto.

EXAMPLES

Preparation of Acrylic Adhesive A

[0069] An acrylic adhesive A was prepared in the following manner. 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 stirred to obtain a reaction liquid. Subsequently, the reaction liquid was supplied to a 40-L polymerization device, and the inside of the polymerization device was set to a nitrogen atmosphere of 80 C. Further, 0.5 parts by weight of benzoyl peroxide was dissolved in 50 parts by weight of cyclohexane, to obtain a polymerization initiator solution. While the polymerization initiator solution was added to the reaction liquid over 24 hours, the monomer was copolymerized. After completion of the copolymerization, ethyl acetate was further added to the reaction liquid, and a solution in which the content of the acrylic adhesive A was 35% by weight was obtained. The solubility parameter of the acrylic adhesive A was 9.0 (cal/cm.sup.3).sup.1/2.

Examples 1 to 21 and Comparative Examples 1 and 2

[0070] An acrylic adhesive A, ethyl cellulose (solubility parameter: 10.3 (cal/cm.sup.3).sup.1/2, trade name ETHOCEL available from DOW Chemical Company), a styrene-isoprene-styrene (SIS) block copolymer (solubility parameter: 8.2 (cal/cm.sup.3).sup.1/2, trade name D1117P available from Kraton Corporation), a terpene resin (solubility parameter: 8.3 (cal/cm.sup.3).sup.1/2, trade name YS RESIN PX1150N available from Yasuhara Chemical Co., Ltd.), a hydrogenated resin of C9-based petroleum resin (solubility parameter: 8.2 (cal/cm.sup.3).sup.1/2, trade name ARKON P-100 available from Arakawa Chemical Industries, Ltd.), a terpene phenolic resin (solubility parameter: 8.8 (cal/cm.sup.3).sup.1/2, trade name YS POLYSTER T115 available from Yasuhara Chemical Co., Ltd.), a liquid paraffin (trade name HICALL M-72 available from Kaneda Co., Ltd.), 2-octyldodecanol, isopropyl myristate, caprylic/capric triglyceride (trade name Triester F-810 available from Nikko Chemicals Co., Ltd.), and rivastigmine were mixed in respective amounts each shown in Tables 1 to 3, to obtain a mixture. Ethyl acetate and toluene were added to the mixture so that the concentration of the solid content was 25% by weight, and then mixed until the mixture was uniform to produce an adhesive layer solution. Herein, caprylic/capric triglyceride is a triester of glycerine, and caprylic acid and capric acid.

[0071] Next, as a release liner, a polyethylene terephthalate film (thickness: 38 m) that had been subjected to a silicone release treatment was prepared. The adhesive layer solution was applied to the silicone release-treated surface of the release liner and dried at 80 C. for 15 minutes to form a layered body in which the adhesive layer (thickness: 100 m) was formed on the silicone release-treated surface of the release liner.

[0072] As a support, a polyethylene terephthalate film (thickness: 25 m) was prepared. The support and the layered body were layered so that the support and the adhesive layer were faced to each other, and the adhesive layer of the layered body was integrally layered on one surface of the support, to obtain an adhesive patch.

Evaluation

[0073] For the adhesive patch obtained in each of Examples and Comparative Examples, a ball tackiness test, a constant load peeling test, a 180 peeling test, and a patch test were performed in the following manner. The obtained results were shown in Tables 1 to 3.

[0074] (Ball Tack Test (Tackiness))

[0075] The adhesive patch was cut at an optional part, to obtain three specimens (22.5 mm in width15 mm in length). For each specimen, a maximum ball number was measured in accordance with an inclined ball tack test specified in JIS 20237 (2009). The arithmetic average of maximum ball numbers of the three specimens was shown in Tables 1 to 3.

[0076] (Constant Load Peeling Test (Cohesive Force))

[0077] The adhesive patch was cut at an optional part, to obtain a rectangular specimen (20 mm in width30 mm in length). Part of the release liner was peeled from the specimen so that a 5-mm terminal of the adhesive layer in the longitudinal direction was exposed. A PET film larger than the exposed part of the adhesive layer was attached to the exposed part of the adhesive layer, to form a clip gripping part. The residual release liner was separated from the specimen, and the specimen was attached to a central part of a rectangular test plate having a test surface formed of an ethylene-vinyl acetate copolymer (EVA) (25 mm in width200 mm in length) using the exposed adhesive layer. An 800-g rubber roller was moved back and forth on the specimen one time, and the specimen was allowed to stand at 40 C. for 30 minutes, to obtain a layered body. The layered body was stretched horizontally in a constant temperature bath of 40 C. with the specimen facing downward. After that, a 1-g metal clip was attached to the clip gripping part, and a 1-g weight was hung on the metal clip to initiate the test. 24 hours after initiation of the test, the longest peeling length (mm) of the specimen peeled from the test plate was measured. From the optional part of the adhesive patch, three specimens were prepared, and the longest peeling lengths of the three specimens were each measured in the aforementioned manner. The arithmetic average thereof was shown in Tables 1 to 3.

[0078] (180 Peeling Test (Adhesive force))

[0079] The adhesive patch was cut at an optional part, to obtain three specimens (22.5 mm in width15 mm in length). For each specimen, a peeling adhesive force (g/25 mm) was measured in accordance with 180 peeling test specified in JIS 20237 (2009).

[0080] The arithmetic average thereof was shown in Tables 1 to 3.

[0081] (Patch Test)

[0082] The adhesive patch was cut at an optional part, to obtain ten specimens (area: 10 cm.sup.2). From each specimen, the release liner was separated, and each specimen was attached to upper arm parts of ten adult healthy men. 24 hours after the attachment, the area of the specimen attached to the skin was measured. The attachment property was evaluated in accordance with the following adhesion scores. The arithmetic average of adhesion score of each specimen was shown in Tables 1 to 3.

Adhesion Score

[0083] 0: the adhesion area was 90% or more.

[0084] 1: the adhesion area was 75% or more and less than 90%.

[0085] 2: the adhesion area was 50% or more and less than 75%.

[0086] 3: the adhesion area was less than 50%, but the specimen was not detached.

[0087] 4: the specimen was detached from the skin.

TABLE-US-00001 TABLE 1 EXAMPLE 1 2 3 4 5 6 7 8 9 FORMULATION ACRYLIC ADHESIVE A 100 100 100 100 100 100 100 100 100 (PART BY SOLID RESIN (S) ETHYL CELLULOSE 16 16 7 17 16 15 17 0 0 WEIGHT) SIS BLOCK COPOLYMER 0 0 0 0 0 0 0 3 6 PLASTICIZER (P.sub.1) LIQUID PARAFFIN 0 8 7 15 16 0 0 7 7 2-OCTYLDODECANOL 20 14 13 15 6 13 15 13 13 ISOPROPYL MYRISTATE 0 0 0 0 0 7 15 0 0 DRUG (P.sub.2) RIVASTIGMINE 20 21 19 22 21 19 22 18 18 RATIO BY WEIGHT [(P.sub.1 + P.sub.2)/S] 2.6 2.7 5.4 3.1 2.7 2.7 3.1 13.5 6.8 EVALUATION BALL TACK TEST MAXIMUM BALL NUMBER 9 10 10 10 9 9 10 10 11 CONSTANT LOAD LONGEST PEELING 0.6 1.3 1.0 1.0 1.0 1.0 1.0 2.7 2.0 PEELING TEST LENGTH (mm) 180 PEELING TEST PEELING ADHESIVE FORCE 181 198 177 217 235 213 247 187 186 (mg/25 mm) PATCH TEST ADHESION SCORE 0 0 0 0 0 0 0 0 0

TABLE-US-00002 TABLE 2 COMPARATIVE EXAMPLE EXAMPLE 10 11 12 13 14 15 16 1 2 FORMULATION ACRYLIC ADHESIVE A 100 100 100 100 100 100 100 100 100 (PART BY SOLID RESIN (S) ETHYL CELLULOSE 0 15 24 7 14 15 15 0 0 WEIGHT) SIS BLOCK COPOLYMER 3 0 0 0 0 0 0 0 0 PLASTICIZER (P.sub.1) LIQUID PARAFFIN 0 0 0 0 0 13 0 0 0 2-OCTYLDODECANOL 20 13 14 12 7 0 0 13 13 ISOPROPYL MYRISTATE 0 0 0 0 0 0 13 0 0 DRUG (P.sub.2) RIVASTIGMINE 18 19 21 18 18 19 19 0 18 RATIO BY WEIGHT [(P.sub.1 + P.sub.2)/S] 13.5 2.2 1.5 4.4 1.8 2.2 2.2 EVALUATION BALL TACK TEST MAXIMUM BALL NUMBER 10 8 7 10 5 10 8 3 13 CONSTANT LOAD LONGEST PEELING 3.0 2.3 4.8 3.0 3.5 3.3 7.4 25 25 PEELING TEST LENGTH (mm) 180 PEELING TEST PEELING ADHESIVE FORCE 199 178 164 154 176 334 464 873 362 (mg/ 25 mm) PATCH TEST ADHESION SCORE 1 1 1 1 1 1 1 2 2

TABLE-US-00003 TABLE 3 EXAMPLE 17 18 19 20 21 FORMULATION ACRYLIC ADHESIVE A 100 100 100 100 100 (PART BY SOLID RESIN (S) ETHYL CELLULOSE 0 0 0 22 0 WEIGHT) SIS BLOCK COPOLYMER 0 0 0 0 0 TERPENE RESIN 16 0 25 0 0 HYDROGENATED RESIN OF C9-BASED 0 15 0 0 22 PETROLEUM RESIN TERPENE PHENOLIC RESIN 0 0 0 22 0 PLASTICIZER (P.sub.1) LIQUID PARAFFIN 24 0 20 31 0 2-OCTYLDODECANOL 0 13 0 0 6 ISOPROPYL MYRISTATE 0 0 0 11 0 CAPRYLIC/CAPRIC TRIGYLCERIDE 0 0 0 11 0 DRUG (P.sub.2) RIVASTIGMINE 21 19 22 24 19 RATIO BY WEIGHT [(P.sub.1 + P.sub.2)/S] 2.8 2.2 1.7 1.8 1.1 EVALUATION BALL TACK TEST MAXIMUM BALL NUMBER 12 14 5 5 10 CONSTANT LOAD LONGEST PEELING 1.8 3.7 4.4 15.1 20.2 PEELING TEST LENGTH (mm) 180 PEELING TEST PEELING ADHESIVE FORCE 307 572 371 618 512 (mg/25 mm) PATCH TEST ADHESION SCORE 0 1 1 2 2

[0088] (Cross-Reference to Related Applications)

[0089] This application claims priority on the basis of Japanese Patent Application No. 2015-16991, filed on Jan. 30, 2015, the disclosure of which is incorporated herein by reference in its entirety.

INDUSTRIAL APPLICABILITY

[0090] The present invention can provide an adhesive patch capable of exerting excellent tackiness to the skin when the adhesive patch is attached and having a low incidence of detachment from the skin during attachment. According to the adhesive patch of the present invention, a drug can be transdermally administered with stability.