CNS PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE

• US 20110054038A1
• Filed: 08/20/2010
• Published: 03/03/2011
• Est. Priority Date: 02/20/2008
• Status: Active Grant

• Current Assignee: Targia Pharmaceuticals
• Original Assignee: Targia Pharmaceuticals
• Inventors: Glozman, Sabina
• Granted Patent: US 8,729,070 B2
• Time in Patent Office: Days
• US Class Current: 514/653
• CPC Class Codes: A61K 31/09 having two or more such linkages
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

The present invention is directed to CNS pharmaceutical compositions and methods of use. The pharmaceutical compositions comprise a CNS active agent and preferably at least two vagal neuromodulators, one of which is a mechanoreceptor stimulator. The vagal neuromodulators are preferably in an amount sufficient to reduce a somnolence side-effect of the CNS active agent without changing its therapeutic efficacy/activity. The invention further encompasses a method of reducing CNS active agent side-effects. The method typically comprises oral administration of at least one CNS active agent to a patient at the conventionally accepted dose; and administration of at least two vagal neuromodulators to the patient so that at least one neuromodulator is administered or released from dosage form after the CNS active agent is administered and/or released.

Claims

1. An oral pharmaceutical composition comprising:

at least one central nervous system (CNS) active agent at a conventionally accepted effective dose;

at least two vagal neuromodulators; and

a pharmaceutically-acceptable vehicle, carrier or diluent, wherein the vagal neuromodulators are in an amount sufficient to reduce a side-effect of the CNS active agent at the conventionally accepted dose and at least one of the vagal neuromodulators is a mechanoreceptor stimulator.

2. The pharmaceutical composition of claim 1, wherein the therapeutic activity of the CNS agent is not reduced by the vagal neuromodulators.

3. The pharmaceutical composition of claim 2, wherein mechanoreceptor stimulator is in a modified release form for co-synchronization with the CNS active agent.

4. The pharmaceutical composition of claim 3, wherein the CNS active agent has a time to maximum concentration (Tmax) and the mechanoreceptor stimulator has a Tmax, and release of the mechanoreceptor stimulator is delayed by an amount of time equal to the Tmax of the CNS active agent minus the Tmax of the mechanoreceptor stimulator plus about 5 to about 45 minutes.

5. The pharmaceutical composition of claim 2, wherein the mechanoreceptor stimulator is guaifenesin (GUA).

7. The pharmaceutical composition of claim 1, wherein the side-effect includes at least one selected from the group consisting of:

sedation, somnolence, sleepnece, memory impairment, amnesia, impairment of cognitive and learning function, ataxia, impaired night sleep/day alertness, impaired memory, impaired concentration, impaired appetite, drowsiness, hypotension, fatigue, kinetic disorders, catalepsy, movement disorders, bowel irritation, and impaired reaction.

9. The pharmaceutical composition of claim 1, wherein at least one CNS agent is GABA inhibitor.

11. The method of claim 9, wherein the CNS active agent has a time to maximum concentration (Tmax and the mechanoreceptor stimulator has a Tmax, and administration or release of the mechanoreceptor stimulator is delayed for an amount of time being equal to the Tmax of the CNS active agent minus the Tmax of the mechanoreceptor stimulator plus about 5 to about 45 minutes.

12. The method of claim 11, wherein the mechanoreceptor stimulator is guaifenesin (GUA).

13. The method claim 11, wherein the at least two vagal neuromodulators comprises pseudoephedrine (PSE).

14. The method of claim 12, wherein the GUA is administered about 5 to about 30 minutes after administration of the CNS active agent.

16. The method of claim 9, wherein the side-effect is reduced without reducing the relevant therapeutic efficacy of the CNS active agent or the conventionally accepted effective dose of the CNS active agent.

6. The pharmaceutical composition of claim 6, wherein the at least two vagal neuromodulators comprise pseudoephedrine (PSE).

8. The pharmaceutical composition of claim 6, wherein the side-effect is sedation-related.

10. A method of reducing a side-effect of a central nervous system (CNS) active agent, the method comprising the steps of:

orally administering to a subject at least one CNS active agent at a conventionally accepted effective dose; and

administering to the patient at least two vagal neuromodulators comprising at least one mechanoreceptor stimulator, wherein the at least two vagal neuromodulators are in an amount sufficient to reduce a side-effect associated with the CNS active agent without reducing the therapeutic efficacy of the CNS agent.

15. The method of claim 10, wherein the side-effect is a sedation-related effect including somnolence.

17. A kit comprising:

an oral dosage of at least one central nervous system (CNS) active agent; and

at least two vagal neuromodulators, wherein the vagal neuromodulators are in an amount sufficient to reduce a side-effect of the CNS active agent and at least one of the vagal neuromodulators is a mechanoreceptor stimulator.

18. The kit of claim 17, wherein the at least one CNS agent and the at least two vagal neuromodulators are in separate dosage forms to be administrated separately or together.

19. The kit of claim 17, wherein the side-effect is a sedation-related effect.

20. The kit of claim 19, wherein the sedation-related effect is somnolence.