JP2012513394A5

JP2012513394A5 -

Info

Publication number: JP2012513394A5
Application number: JP2011542272A
Authority: JP
Filing date: 2009-12-10
Publication date: 2016-08-12
Anticipated expiration: 2029-12-10

Description

いくつかの実施形態において、グルタミン酸受容体アンタゴニストは、NMDA受容体アンタゴニストである。いくつかの実施形態において、NMDA受容体を調節する薬剤は、NMDA受容体アンタゴニストである。いくつかの実施形態において、グルタミン酸受容体アンタゴニストは、1-アミノアダマンタン、デキストロメトルファン、デキストロルファン、イボガイン、イフェンプロジル、(S)-ケタミン、(R)-ケタミン、メマンチン、ジゾシルピン(MK-801)、ガシクリジン、AM-101、トラキソプロジル、D-2-アミノ-5-ホスホノペンタン酸(D-AP5)、3-((±)2-カルボキシピペラジン-4-イル)-プロピル-1-ホスホン酸(CPP)、コナントキン、7-クロロキヌレネート(7-CK)、リコスチネル、亜酸化窒素、フェンシクリジン、リルゾール、チレタミン、アプチガネル、レマシミド(remacimide)、DCKA(5、 7-ジクロロキヌレン酸)、キヌレン酸、1-アミノシクロプロパンカルボン酸(ACPC)、AP7(2-アミノ-7-ホスホノヘプタン酸)、APV(R-2-アミノ-5-ホスホノペンタノアート、CPPene(3-[(R)-2-カルボキシピペラジン-4-イル]-1-プロペニル-1-ホスホン酸、(+)-(1S,2S)-1-(4-ヒドロキシフェニル)-2-(4-ヒドロキシ-4-フェニルピペリジノ)-1-プロパノール、(1S,2S)-1-(4-ヒドロキシ-3-メトキシフェニル)-2-(4-ヒドロキシ-4-フェニルピペリジノ)-1-プロパノール、(3R,4S)-3-(4-(4-フルオロフェニル)-4-ヒドロキシピペリジン-1-イル)-クロマン-4,7-ジオール、(1R*,2R*)-1-(4-ヒドロキシ-3-メチルフェニル)-2-(4-(4-フルオロフェニル)-4-ヒドロキシピペリジン-1-イル)-プロパン-1-オールメシル酸塩、またはそれらの組み合わせである。いくつかの実施形態において、NMDA受容体アンタゴニストは、アリールシクロアルキルアミンである。いくつかの実施形態において、NMDA受容体アンタゴニストは(S)-ケタミンまたはその塩である。いくつかの実施形態においてNMDA受容体アンタゴニストは、キナゾリンである。いくつかの実施形態において、NMDA受容体アンタゴニストは7-CKまたはその塩である。いくつかの実施形態において、NMDA受容体アンタゴニストはAM-101またはその塩である。
In some embodiments, the glutamate receptor antagonist is an NMDA receptor antagonist. In some embodiments, the agent that modulates an NMDA receptor is an NMDA receptor antagonist. In some embodiments, the glutamate receptor antagonist is 1-aminoadamantane, dextromethorphan, dextrorphan, ibogaine, ifenprodil, (S) -ketamine, (R) -ketamine, memantine, dizocilpine (MK-801) , Gacyclidine, AM-101, traxoprodil, D-2-amino-5-phosphonopentanoic acid (D-AP5), 3-((±) 2-carboxypiperazin-4-yl) -propyl-1-phosphonic acid ( CPP), conantoquin, 7-chloroquinurenate (7-CK), lycostine, nitrous oxide, phencyclidine, riluzole, tiletamine, aptiganel, remacimide, DCKA (5, 7-dichloroquinurenic acid), Kynurenic acid, 1-aminocyclopropanecarboxylic acid (ACPC), AP7 (2-amino-7-phosphonoheptanoic acid), APV (R-2-amino-5-phosphonopentanoate, CPPene (3-[( R) -2-Carboxypiperazi 4-yl] - 1-pro pane-l-phosphonic acid, (+) - (1S, 2S) -1- (4-hydroxy Schiff Eniru) -2- (4-hydroxy-4-phenylpiperidino ) -1-profile path no le, (1S, 2S) -1- (4-hydroxy-3-methoxyphenyl) -2- (4-hydroxy-4-Fenirupipe lysine Roh) -1-propanol Le, (3R , 4S) -3- (4- (4- fluorophenyl) -4-hydroxypiperidine-1-b le) - chroman-4,7 Jio Le, (1R *, 2R *) - 1- (4- hydroxy 3-methylphenyl) -2- (4- (4-fluoride Mikhailov Eniru) -4-hydroxypiperidine-1-yl) -. a propane-1-O-le main sill acid salt or combinations thereof, a number In some embodiments, the NMDA receptor antagonist is an arylcycloalkylamine.In some embodiments, the NMDA receptor antagonist is (S) -ketamine or a salt thereof.In some embodiments, the NMDA receptor Body antagonist is quinazo In some embodiments, the NMDA receptor antagonist is 7-CK or a salt thereof In some embodiments, the NMDA receptor antagonist is AM-101 or a salt thereof.

Claims

A sterile pharmaceutical compositions for use in the treatment of tinnitus occurs with hourglass by that Xing奮毒or excitotoxic indoors administration in the round window membrane or the round window membrane near the ear ,
The pharmaceutical composition comprises
(I) include a polyoxypropylene and polyoxyethylene polymers acceptable to the ear containing a thermoreversible aqueous gel, an ear sensory cells regulators that are not fine powdered by and coating,
And,
(Ii) such that the sustained release of the ear sensory cell modulator to the cochlea occurs for at least 5 days;
The ear sensory cell modulator is 1-aminoadamantane, dextromethorphan, dextrorphan, ibogaine, ifenprodil, (S) -ketamine, (R) -ketamine, memantine, dizocilpine (MK-801), gacyclidine, traxoprodil, D 2-amino-5-phosphonopentanoic acid (D-AP5), 3-((±) 2-carboxypiperazin-4-yl) -propyl-1-phosphonic acid (CPP), conanthquine, 7-chloroquinure sulfonates (7-CK), Rikosuchineru, full Enshikurijin, riluzole, tiletamine, aptiganel, Remashimido, DCKA (5,7-dichloro-silk Ren acid), kynurenic acid, 1-amino cyclopropane carboxylic acid (ACPC), AP7 (2- Amino-7-phosphonoheptanoic acid), APV (R-2-A Bruno 5- phosphono pentanoate), CPPene (3 - [( R) -2- carboxy-piperazin-4-yl] - 1-pro pane-l-phosphonic acid), (+) - (1S , 2S ) -1- (4-hydroxy Schiff Eniru) -2- (4-hydroxy-4-phenylpiperidino) -1-profile path no le, (1S, 2S) -1- (4-hydroxy-3- methoxyphenyl) -2- (4-hydroxy-4-Fenirupipe lysine Roh) -1-propanol Le, (3R, 4S) -3- ( 4- (4- fluorophenyl) -4-hydroxypiperidine-1-b le ) - chroman-4,7 Jio Le, (1R *, 2R *) - 1- (4- hydroxy-3-methylphenyl) -2- (4- (4-fluoride Mikhailov Eniru) -4-hydroxypiperidine - 1-yl) - propane-1-O-le main Le salt, or a salt thereof, or a pharmaceutical composition which is a combination thereof.

The composition according to claim 1, wherein the ear sensory cell modulator is (S) -ketamine or a salt thereof, or 7-CK or a salt thereof.

The composition according to claim 1, wherein the ear sensory cell regulator is gacyclidine or a salt thereof.

The composition according to any one of claims 1 to 3 , wherein the polymer of polyoxypropylene and polyoxyethylene is poloxamer 407.

The composition according to any one of claims 1 to 4 , which is a sterile pharmaceutical composition for use in the treatment of tinnitus caused by excitotoxicity .

6. The composition according to any one of claims 1 to 5 , wherein the ear sensory cell modulator is gradually released to the cochlea for at least 7 days.

A composition according to any one of claims 1 to 6 wherein the composition to provide a real osmolality of 300 mOsm / L 250.