Patch and method for producing the same

Patent metadata

Field	Value
Publication number	US-10080738-B2
Application number	US-201615331939-A
Country	US
Kind code	B2
Filing date	Oct 24, 2016
Priority date	Jul 26, 2012
Publication date	Sep 25, 2018
Grant date	Sep 25, 2018

Abstract

A method for producing a patch comprising a support layer and an adhesive agent layer comprises:
a mixture preparation step of mixing asenapine or a pharmaceutically acceptable salt thereof with sodium acetate whose particle diameter D 50 at a cumulative volume of 50% in a particle diameter distribution is 40 to 1000 μm, in such a manner that the sodium acetate and sodium diacetate generated from the sodium acetate have a particle diameter D 50 of 10 μm or smaller, thereby obtaining a mixture containing the sodium diacetate and the asenapine or pharmaceutically acceptable salt; and an adhesive-agent-layer formation step of forming the adhesive agent layer comprising the sodium diacetate, the asenapine or pharmaceutically acceptable salt, and a pressure-sensitive adhesive base agent, by using an adhesive agent layer composition obtained by mixing the mixture with the pressure-sensitive adhesive base agent.

First claim

The invention claimed is:

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 asenapine maleate,
wherein the sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or asenapine maleate, the sodium diacetate has a particle diameter D 50 of 10 μm or smaller, the asenapine and/or asenapine maleate has a content in terms of free asenapine in a range of 1% to 15% relative to the adhesive agent layer, a mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.5 to 1:4, the adhesive agent layer measured by X-ray diffraction has a peak intensity from the sodium diacetate which is higher than a peak intensity from sodium acetate, and when a content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC 2-120 of free asenapine for a period starting from the time when the patch is brought into contact with skin for 24 hours is 8,077 pg·hr/mL or more.

2. The patch according to claim 1 , wherein the adhesive agent layer comprises the asenapine maleate.

3. The patch according to claim 1 , wherein the adhesive agent layer further comprises an absorption enhancer.

4. The patch according to claim 3 , wherein a mass ratio of the asenapine and/or asenapine maleate to the absorption enhancer where a mass of the asenapine and/or asenapine maleate is in terms of free asenapine is in a range of 1:0.1 to 1:10.

5. The patch according to claim 1 , wherein the content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is in a range of 1.5% to 12% relative to the adhesive agent layer.

6. The patch according to claim 1 , wherein an AUC 2-120 of an asenapine metabolite is 20% or less of the AUC 2-120 of the free asenapine.

7. The patch according to claim 2 , wherein an AUC 2-120 of an asenapine metabolite is 20% or less of an AUC 2-120 of free asenapine.

8. The patch according to claim 1 , wherein the sodium diacetate has a content in a range of 0.3% to 10% or less relative to the adhesive agent layer.

9. The patch according to claim 1 , wherein the sodium diacetate has a content in a range of 0.5% to 6% or less relative to the adhesive agent layer.

10. The patch according to claim 5 , wherein the sodium diacetate has a content in a range of 0.3% to 10% or less relative to the adhesive agent layer.

11. The patch according to claim 5 , wherein the sodium diacetate has a content in a range of 0.5% to 6% or less relative to the adhesive agent layer.

12. The patch according to claim 1 , wherein the mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.75 to 1:2.

13. The patch according to claim 12 , wherein the sodium acetate has a content of 10% or less relative to the adhesive agent layer.

14. The patch according to claim 12 , wherein the sodium acetate has a content of 5% or less relative to the adhesive agent layer.

15. 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 sodium diacetate, a pressure-sensitive adhesive base agent, and at least one of asenapine and asenapine maleate such that when a content of the asenapine and/or asenapine maleate in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC 2-120 of free asenapine for a period starting from the time when the patch is brought into contact with the skin for 24 hours is 8,077 pg·hr/mL or more,
wherein the sodium diacetate is generated from sodium acetate in the presence of the asenapine and/or asenapine maleate, the sodium diacetate has a particle diameter IC 50 of 10 μm or smaller, the asenapine and/or asenapine maleate has a content in terms of free asenapine in a range of 1% to 15% relative to the adhesive agent layer, a mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.5 to 1:4, and the adhesive agent layer measured by X-ray diffraction has a peak intensity from the sodium diacetate which is higher than a peak intensity from sodium acetate.

16. The method of claim 15 , wherein an AUC 2-120 of an asenapine metabolite is 20% or less of the AUC 2-120 of the free asenapine.

17. The method of claim 15 , wherein the adhesive agent layer comprises the asenapine maleate.

18. The method of claim 15 , wherein the adhesive agent layer further comprises an absorption enhancer.

19. The method of claim 15 , wherein the central nervous system disease is schizophrenia.

20. The method of claim 15 , wherein the mole ratio of the asenapine and/or asenapine maleate to the sodium diacetate is in a range of 1:0.75 to 1:2.

Assignees

• Hisamitsu Pharmaceutical Co
• Hisamitsu Pharmaceutical Co Ltd

Inventors

• Suzuki Masayuki
• Okutsu Hiroaki
• Yasukochi Takashi
• Takada Yasunori

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K9/7061

  Polyacrylates · CPC title

• A61K31/407 Primary

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title