By a News Reporter-Staff News Editor at Drug Week A patent application by the inventors SUZUKI, Masayuki (Tsukuba-shi, JP); OKUTSU, Hiroaki (Tsukuba-shi, JP); YASUKOCHI, Takashi (Tsukuba-shi, JP); TAKADA, Yasunori (Tsukuba-shi, JP), filed on March 9, 2017, was made available online on June 29, 2017, according to news reporting originating from Washington, D.C., by NewsRx correspondents (see also Hisamitsu Pharmaceutical Co., Inc.).
This patent application is assigned to Hisamitsu Pharmaceutical Co., Inc.
The following quote was obtained by the news editors from the background information supplied by the inventors: "Asenapine (trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[- 4,5-c]pyrrole) is a compound having a central nervous system (CNS)-suppressing activity, an anti-histamine activity, and an anti-serotoninergic activity. Asenapine is known as a drug for use in the treatment of central nervous system diseases such as schizophrenia.
"For example, International Publication No. WO2010/127674 (PTL 1) describes pharmaceutical preparations containing asenapine, in the form of topical agents such as sprays, aerosols, patches, and ointments. Moreover, International Publication No. WO2011/136283 (PTL 2) describes a transdermal preparation containing a skin irritation suppressant including a cholesterol compound, a drug, and a pharmaceutical ingredient. PTL 2 cites asenapine as the drug, and also cites lauric acid diethanolamine, propylene glycol monolaurate, and sorbitan monolaurate as the pharmaceutical ingredient. However, such conventional pharmaceutical preparations containing asenapine have a problem that an adverse effect is likely to occur. In addition, particularly, such topical agents have a problem that it is difficult to keep the plasma concentration of asenapine at a therapeutically effective level.
"On the other hand, heretofore, various patches have been developed in order to improve the skin permeability of a drug contained in the patches. For example, International Publication No. WO01/07018 (PTL 3) discloses a patch containing a basic drug, an organic acid, and an organic acid salt. PTL 3 discloses acetic acid, lactic acid, and the like as the organic acid, and sodium acetate and the like as the organic acid salt. Further, for example, International Publication No. WO2005/115355 (PTL 4) discloses that a patch containing a basic drug and a volatile organic acid further contains an organic acid salt. Furthermore, PTLs 3 and 4 state that the patches may further contain an absorption enhancer (permeation enhancer), and cite various compounds as the absorption enhancer, such as lauryl alcohol, 1-menthol, propylene glycol, pirotiodecane, sorbitan monolaurate, isostearyl alcohol, lauric acid diethanolamide, propylene glycol monolaurate, glycerin monolaurate, lauric acid, and isopropyl myristate."
In addition to the background information obtained for this patent application, NewsRx journalists also obtained the inventors' summary information for this patent application: "Technical Problems
"However, the cited literatures 3 and 4 do not disclose at all a patch using asenapine as a drug. Meanwhile, the present inventors have found that when a pharmaceutical preparation containing asenapine is administered, increasing the amount of asenapine shifted into plasma, in other words, the area under plasma concentration-time curve (AUC) of free asenapine, also increases the amount of an asenapine metabolite in the plasma (the AUC of the asenapine metabolite), so that the incidence proportion of adverse effects is increased.
"The present invention has been made in view of the problems of the conventional techniques, and an object of the present invention is to provide a patch capable of achieving a therapeutically effective level of plasma concentration of asenapine which is sufficiently higher than ever achieved, and also capable of sufficiently suppressing the plasma concentration of an asenapine metabolite.
"Solution to Problems
"The present inventors have conducted earnest study to achieve the above object. As a result, the inventors have found that incorporating a combination of asenapine and/or a pharmaceutically acceptable salt thereof, isopropyl palmitate, and an adhesive base agent into an adhesive agent layer of a patch comprising a support layer and the adhesive agent layer enables the skin permeability of asenapine to be sufficiently high, and makes it possible to achieve a therapeutically effective level of plasma concentration of asenapine which is sufficiently higher than ever achieved. Further, the inventors have found that administering asenapine us ing such a patch can sufficiently suppress the plasma concentration of an asenapine metabolite. These findings have led to the completion of the present invention.
"Specifically, a patch of the present invention is a patch comprising a support layer and an adhesive agent layer, characterized in that the adhesive agent layer comprises asenapine and/or a pharmaceutically acceptable salt thereof, isopropyl palmitate, and an adhesive base agent.
"Moreover, in the patch of the present invention, a mass ratio of the asenapine and/or pharmaceutically acceptable salt to the isopropyl palmitate (a mass of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine:a mass of the isopropyl palmitate) in the adhesive agent layer is preferably 1:0.1 to 1:10.
"Further, in the patch of the present invention, the adhesive agent layer preferably further comprises sodium diacetate; more preferably, a mole ratio of the asenapine and/or pharmaceutically acceptable salt to the sodium diacetate (the number of moles of the asenapine and/or pharmaceutically acceptable salt:the number of moles of the sodium diacetate) in the adhesive agent layer is 1:0.5 to 1:4.
"In addition, in the patch of the present invention, the adhesive base agent is preferably at least one selected from the group consisting of (meth)acrylic ester (co)polymers, rubber-based adhesive agents, silicone polymers, and polyurethane-based adhesive agents.
"Furthermore, in the patch of the present invention, preferably, when a content of the asenapine and/or pharmaceutically acceptable salt in terms of free asenapine is 3.4 mg in the adhesive agent layer,
"an area under plasma concentration-time curve of the free asenapine between 2 and 120 hours for a period starting from the time when the patch is brought into contact with skin for 24 hours (AUC.sub.2-120) 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.
"Advantageous Effects of Invention
"The present invention makes it possible to provide a patch capable of achieving a therapeutically effective level of plasma concentration of asenapine which is sufficiently higher than ever achieved, and also capable of sufficiently suppressing the plasma concentration of an asenapine metabolite."
URL and more information on this patent application, see: SUZUKI, Masayuki; OKUTSU, Hiroaki; YASUKOCHI, Takashi; TAKADA, Yasunori. Patch. Filed March 9, 2017 and posted June 29, 2017. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220170172981%22.PGNR.&OS=DN/20170172981&RS=DN/20170172981
Keywords for this news article include: Hisamitsu Pharmaceutical Co. Inc., Asenapine, Drugs and Therapies, Atypical Antipsychotics, Psychotherapeutic Agents.
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