Claims for Patent: 10,583,121

Summary for Patent: 10,583,121

Title:	Patch
Abstract:	A patch for administering asenapine includes a support layer, and an adhesive agent layer formed on the support layer and including an adhesive base agent and asenapine and/or a pharmaceutically acceptable salt thereof. The adhesive base agent has a content in a range of 10 to 90% by mass in the adhesive agent layer and includes a natural rubber, polyisobutylene, an alkyl vinyl ether(co)polymer, polyisoprene, polybutadiene, a styrene-butadiene copolymer, a styrene-isoprene copolymer, a styrene-isoprene-styrene block copolymer, or a combination thereof. When a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC.sub.2-120 for a period starting from the time when the patch is brought into contact with a skin for 24 hours is 27,000 pghr/mL or more, and an AUC.sub.2-120 of an asenapine metabolite is 20% or less of the AUC.sub.2-120 of the free asenapine.
Inventor(s):	Suzuki; Masayuki (Tsukuba, JP), Okutsu; Hiroaki (Tsukuba, JP), Yasukochi; Takashi (Tsukuba, JP), Takada; Yasunori (Tsukuba, JP)
Assignee:	HISAMITSU PHARMACEUTICAL CO., INC. (Tosu-shi, JP)
Application Number:	15/454,066
Patent Claims:	1. A patch for administering asenapine, comprising: a support layer; and an adhesive agent layer formed on the support layer and comprising an adhesive base agent, sodium diacetate, isopropyl palmitate, and at least one of asenapine and a pharmaceutically acceptable salt thereof, wherein the adhesive base agent has a content in a range of 10 to 90% by mass in the adhesive agent layer and comprises a styrene-isoprene-styrene block copolymer, and the adhesive agent layer is formulated such that when a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC.sub.2-120 of the free asenapine for a period starting from the time when the patch is brought into contact with a skin for 24 hours achieves a therapeutically effective level of 27,000 pg-hr/mL or more, while an AUC.sub.2-120 of an asenapine metabolite is suppressed to 20% or less of the AUC.sub.2-120 of the free asenapine. 2. The patch of claim 1, wherein a mole ratio of the asenapine and/or pharmaceutically acceptable salt to the sodium diacetate in the adhesive agent layer is in a range of 1:0.5 to 1:4. 3. The patch of claim 1, wherein the pharmaceutically acceptable salt is asenapine maleate. 4. The patch of claim 1, wherein a content of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine in the adhesive agent layer is in a range of 1 to 15% by mass. 5. The patch of claim 1, wherein a mass ratio of a mass of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine to a mass of the isopropyl palmitate in the adhesive agent layer is in a range of 1:0.1 to 1:10. 6. The patch of claim 1, wherein the adhesive agent layer further comprises a tackifier. 7. The patch of claim 6, wherein a mass ratio of the content of the adhesive base agent to a content of the tackifier in the adhesive agent layer is in a range of 1:6 to 1.5:1. 8. The patch of claim 1, wherein the adhesive agent layer further comprises a softener. 9. The patch of claim 8, wherein a mass ratio of the content of the adhesive base agent to a content of the softener in the adhesive agent layer is in a range of 1:6 to 5:1. 10. The patch of claim 1, wherein a mole ratio of the asenapine and/or pharmaceutically acceptable salt to the sodium diacetate in the adhesive agent layer is in a range of 1:0.5 to 1:4, and a content of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine in the adhesive agent layer is in a range of 1 to 15% by mass. 11. A method for treating a central nervous system disease, comprising: administering asenapine to a patient in need thereof by applying, on a skin of the patient, a patch comprising a support layer and an adhesive agent layer formed on the support layer and comprising an adhesive base agent, sodium diacetate, isopropyl palmitate, and at least one of asenapine and a pharmaceutically acceptable salt thereof, wherein the adhesive base agent has a content in a range of 10 to 90% by mass in the adhesive agent layer and comprises a styrene-isoprene-styrene block copolymer, and the adhesive agent layer is formulated such that when a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC.sub.2-120 of the free asenapine for a period starting from the time when the patch is brought into contact with a skin for 24 hours achieves a therapeutically effective level of 27,000 pghr/mL or more, while an AUC.sub.2-120 of an asenapine metabolite is suppressed to 20% or less of the AUC.sub.2-120 of the free asenapine. 12. The method of claim 11, wherein a mole ratio of the asenapine and/or pharmaceutically acceptable salt to the sodium diacetate in the adhesive agent layer is in a range of 1:0.5 to 1:4. 13. The method of claim 11, wherein the pharmaceutically acceptable salt is asenapine maleate. 14. The method of claim 11, wherein a content of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine in the adhesive agent layer is in a range of 1 to 15% by mass. 15. The method of claim 11, wherein a mass ratio of a mass of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine to a mass of the isopropyl palmitate in the adhesive agent layer is in a range of 1:0.1 to 1:10. 16. The method of claim 11, wherein the adhesive agent layer further comprises a tackifier. 17. The method of claim 16, wherein a mass ratio of the content of the adhesive base agent to a content of the tackifier in the adhesive agent layer is in a range of 1:6 to 1.5:1. 18. The method of claim 11, wherein the adhesive agent layer further comprises a softener. 19. The method of claim 18, wherein a mass ratio of the content of the adhesive base agent to a content of the softener in the adhesive agent layer is in a range of 1:6 to 5:1. 20. The method of claim 11, wherein a mole ratio of the asenapine and/or pharmaceutically acceptable salt to the sodium diacetate in the adhesive agent layer is in a range of 1:0.5 to 1:4, and a content of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine in the adhesive agent layer is in a range of 1 to 15% by mass.