Controlled-release CNS modulating compositions and methods for the treatment of otic disorders

Patent metadata

Field	Value
Publication number	US-9333171-B2
Application number	US-201414300011-A
Country	US
Kind code	B2
Filing date	Jun 9, 2014
Priority date	Jun 27, 2008
Publication date	May 10, 2016
Grant date	May 10, 2016

Abstract

Disclosed herein are compositions and methods for the treatment of otic disorders with CNS modulating agent compositions and compositions administered locally to an individual afflicted with an otic disorder, through direct application of these compositions and compositions onto or via perfusion into the targeted auris structure(s).

First claim

We claim:

1. An intratympanic composition for use in the treatment of an otic disease or condition by administration on or near the round window membrane of the ear, the intratympanic composition comprising
a micronized Central Nervous System (CNS) modulator, or pharmaceutically acceptable salt thereof; and
an auris acceptable gel, wherein the auris acceptable gel has a viscosity between about 15,000 cP and about 1,000,000 cP,
wherein the micronized Central Nervous System (CNS) modulator, or pharmaceutically acceptable salt thereof is not provided as polymer-containing particles, and is suspended in the auris acceptable gel; and wherein sustained release of the CNS modulator into the cochlea occurs for a period of at least 5 days after a single administration.

2. The intratympanic composition of claim 1 , wherein the auris acceptable gel is an auris acceptable hydrogel.

3. The intratympanic composition of claim 1 , wherein the auris acceptable gel is capable of being injected by a narrow gauge needle or cannula through the tympanic membrane to an area on or near the round window membrane.

4. The intratympanic composition of claim 1 , wherein the intratympanic composition has an osmolarity of from about 150 mOsm/L to about 1000 mOsm/L.

5. The intratympanic composition of claim 1 , wherein the intratympanic composition has a pH between 7.0 and 8.0.

6. The intratympanic composition of claim 1 , wherein the CNS modulator is a GABA receptor modulator or an antihistamine.

7. The intratympanic composition of claim 6 , wherein the antihistamine is selected from meclizine, diphenhydramine, dimenhydrinate, loratadine, quetiapine, mepyramine, piperoxan, antazoline, carbinoxamine, doxylamine, clemastine, pheniramine, chlorphenamine, chlorpheniramine, dexchlorpheniramine, brompheniramine, triprolidine, cyclizine, chlorcyclizine, hydroxyzine, promethazine, alimemazine, trimeprazine, cyproheptadine, azatadine, ketotifen, oxatomide and betahistine.

8. The intratympanic composition of claim 6 , wherein the GABA receptor modulator agonizes the activity of a GABA receptor.

9. The intratympanic composition of claim 6 , wherein the GABA receptor modulator partially or fully inhibits the repolarization of a neuron.

10. The intratympanic composition of claim 6 , wherein the GABA receptor modulator is selected from a benzodiazepine, a loop diuretic, or a GABA analogue.

11. The intratympanic composition of claim 6 , wherein the GABA receptor modulator is selected from alprazolam, bromazepam, brotizolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, loprazolam, lorazepam, lormetazepam, idazolam, nimetazepam, nitrazepam, oxazepam, prazepam, temazepam, and triazolam or combinations thereof.

12. The intratympanic composition of claim 1 , wherein the otic disease or condition is endolymphatic hydrops, kinetosis, labyrinthitis, mal de debarquement, Meniere's disease, Meniere's syndrome, Ramsay Hunt's syndrome (Herpes zoster infection), recurrent vestibulopathy, tinnitus, vertigo, microvascular compression syndrome, utricular dysfunction, vestibular neuronitis, benign paroxysmal positional vertigo, or combinations thereof.

13. The intratympanic composition of claim 1 , wherein the otic disease or condition is tinnitus.

14. The intratympanic composition of claim 1 , wherein sustained release of the CNS modulator into the cochlea occurs for a period of at least 7 days after a single administration.

15. The intratympanic composition of claim 1 , wherein sustained release of the CNS modulator into the cochlea occurs for a period of at least 10 days after a single administration.

Assignees

• Otonomy Inc
• Univ California

Inventors

• Lichter Jay
• Trammel Andrew M
• Piu Fabrice
• Ye Qiang
• Scaife Michael Christopher
• Vollrath Benedikt
• Duron Sergio G
• Dellamary Luis A
• Lebel Carl
• Harris Jeffrey P

Classifications

• A61P27/16

  Otologicals · CPC title

• A61K31/195

  having an amino group · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• A61K9/0046 Primary

  Ear · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title