Claims for Patent: 10,814,002

Summary for Patent: 10,814,002

Title:	Patch and method for producing the same
Abstract:	A method for producing a patch including a support layer, and an adhesive agent layer formed on the support layer and including sodium diacetate, a pressure-sensitive adhesive base agent, and asenapine and/or a pharmaceutically acceptable salt thereof. The sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or salt thereof, a content of the asenapine and/or salt thereof in terms of free asenapine in the adhesive agent layer is in range of 3.0 to 20 mg, and when a content of the asenapine and/or salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, C.sub.max of free asenapine is in range of 0.5 to 6.0 ng/mL and t.sub.max of free asenapine is in range of 8 to 28 hr.
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:	16/209,084
Patent Claims:	1. A patch for administering asenapine, comprising: a support layer; and an adhesive agent layer formed on the support layer and comprising sodium diacetate, a pressure-sensitive adhesive base agent, and at least one of asenapine and a pharmaceutically acceptable salt thereof, wherein the sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or pharmaceutically acceptable salt thereof, the adhesive agent layer has an area of an application surface per the patch in a range of 20 to 40 cm.sup.2, a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is in a range of 6.4 to 12.8 mg, and when a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, a Cmax of free asenapine is in a range of 0.5 to 6.0 ng/mL and a tmax of free asenapine is in a range of 8 to 28 hr. 2. The patch according to claim 1, wherein when the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, an AUC0-inf of free asenapine is 36 nghr/mL or more. 3. The patch according to claim 1, wherein when the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, a t1/2 of free asenapine is in a range of 17 to 55 hr. 4. The patch according to claim 1, wherein when the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, a Cmax of an asenapine metabolite is 20% or less of the Cmax of free asenapine. 5. The patch according to claim 1, wherein when the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, an AUC0-inf of an asenapine metabolite is 22% or less of an AUC0-inf of free asenapine. 6. The patch according to claim 1, wherein when the patch is in contact with skin once daily for 7 days, a Dopamine D2 receptor occupancy of free asenapine is in a range of 14 to 70%. 7. The patch according to claim 1, wherein the adhesive agent layer further comprises an absorption enhancer. 8. The patch according to claim 1, wherein the adhesive agent layer has the area of the application surface per the patch of 20 cm.sup.2 . 9. The patch according to claim 1, wherein the adhesive agent layer has the area of the application surface per the patch of 40 cm.sup.2 . 10. The patch according to claim 1, wherein the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg. 11. The patch according to claim 1, wherein the pharmaceutically acceptable salt of asenapine is asenapine maleate. 12. The patch according to claim 11, wherein when the content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, an AUC0-inf of free asenapine is 36 nghr/mL or more. 13. The patch according to claim 11, wherein when the content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, a t1/2 of free asenapine is in a range of 17 to 55 hr. 14. The patch according to claim 11, wherein when the content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, a Cmax of an asenapine metabolite is 20% or less of the Cmax of free asenapine. 15. The patch according to claim 11, wherein when the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 6.4 mg and the patch is in contact with skin for 24 hours, an AUC0-inf of an asenapine metabolite is 22% or less of an AUC0-inf of free asenapine. 16. The patch according to claim 11, wherein when the patch is in contact with skin once daily for 7 days, a Dopamine D2 receptor occupancy of free asenapine is in a range of 14 to 70%. 17. The patch according to claim 1, wherein the content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 12.8 mg. 18. A method for treating schizophrenia, comprising: administering the patch of claim 1 to a patient in need thereof. 19. A method for treating schizophrenia, comprising: administering the patch of claim 7 to a patient in need thereof. 20. A method for treating schizophrenia, comprising: administering the patch of claim 11 to a patient in need thereof.