MEMANTINE COMBINATIONS AND USE

• US 20180116979A1
• Filed: 10/27/2017
• Published: 05/03/2018
• Est. Priority Date: 10/28/2016
• Status: Active Grant

• Current Assignee: Chase Pharmaceuticals Corp. (Abbvie Incorporated)
• Original Assignee: Chase Pharmaceuticals Corp. (Abbvie Incorporated)
• Inventors: CLARENCE-SMITH, Kathleen E., CHASE, Thomas N.
• Granted Patent: US 10,548,855 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Abstract

A pharmaceutical combination of memantine and a non-anticholinergic antiemetic agent for the treatment of hypocholinergic disorders in further combination with high doses of donepezil and with solifenacin, and kits comprising said combination. A pharmaceutical combination of memantine and solifenacin for the treatment of hypocholinergic disorders, including Alzheimer type dementia, in further combination with high doses of donepezil, and kits comprising said combination.

Claims

1. A pharmaceutical combination comprising, as Components,

(a) memantine or a pharmaceutically acceptable salt thereof;

and

(b) a non-anticholinergic antiemetic agent (naAEA).

2. The combination of claim 1, wherein said memantine or a pharmaceutically acceptable salt thereof Component (a) is in a pharmaceutical composition in dosage unit form, in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier;

and said naAEA Component (b) is in a pharmaceutical composition in dosage unit form, in admixture with a pharmaceutical carrier.

3. The combination of claim 1, wherein said combination is a fixed-dose combination essentially consisting of a pharmaceutical composition comprising

(a) said memantine or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride;

and

(b) said naAEA is selected from the group consisting of alosetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in alosetron) of from 0.25 mg to 6 mg;

azasetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in azasetron) of from 5 mg to 60 mg;

dolasetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in dolasetron) of from 25 mg to 600 mg;

granisetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in granisetron) of from 0.5 mg to 6 mg;

ondansetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in ondansetron) of from 2 mg to 64 mg;

palonosetron and pharmaceutically acceptable salts and solvated thereof, in an amount (in palonosetron) of from 0.25 mg to 3 mg;

ramosetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in ramosetron) of from 0.0125 mg to 0.3 mg;

tropisetron and pharmaceutically acceptable salts and solvates thereof, in an amount of from 2.5 mg to 30 mg;

domperidone and pharmaceutically acceptable salts and solvates thereof, in an amount (in domperidone) of from 5 mg to 60 mg;

haloperidol, in an amount of from 0.5 mg to 60 mg;

chlorpromazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in chlorpromazine) of from 12.5 mg to 600 mg;

prochlorperazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in prochlorperazine) of from 2.5 mg to 30 mg;

metoclopramide and pharmaceutically acceptable salts and solvates thereof, in an amount (in metoclopramide) of from 5 mg to 60 mg;

bromopride and pharmaceutically acceptable salts and solvates thereof, in an amount (in bromopride) of from 5 mg to 60 mg;

clebopride and pharmaceutically acceptable salts and solvates thereof, in an amount (in clebopride) of from 0.25 mg to 3 mg;

levosulpiride, in an amount of from 12.5 mg to 600 mg;

alizapride and pharmaceutically acceptable salts thereof, in an amount (in alizapride) of from 25 mg to 300 mg;

trimethobenzamide and pharmaceutically acceptable salts thereof, in an amount (in trimethobenzamide) of from 50 mg to 600 mg;

meclizine (also called meclozine) and pharmaceutically acceptable salts and solvates thereof, in an amount (in meclizine) of from 6.25 mg to 300 mg;

promethazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in promethazine) of from 12.5 mg to 150 mg;

dronabinol in an amount of from 1.25 mg to 60 mg;

nabilone, in an amount of from 0.5 mg to 6 mg;

aprepitant, in an amount of from 20 mg to 750 mg;

netupitant, in an amount of from 150 mg to 1800 mg;

rolapitant, in an amount of from 30 mg to 360 mg; and

casopitant, in an amount of from 25 mg to 300 mg, in admixture with a pharmaceutical carrier or vehicle.

4. The combination of claim 3, wherein said naAEA is a fixed dose combination comprising palonosetron hydrochloride, in an amount of 0.5 mg, and netupitant, in an amount of 300 mg, in admixture with a pharmaceutical carrier or vehicle.

5. The combination according to any one of claims 1, for use for the treatment of a hypocholinergic disorder, in further combination with

(c) a pharmaceutically composition in dosage unit form comprising donepezil or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 10 mg to 92 mg of donepezil hydrochloride, in admixture with a pharmaceutical carrier or vehicle;

and

(d) a pharmaceutically composition in dosage unit form comprising solifenacin or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate, in admixture with a pharmaceutical carrier or vehicle.

6. A method for the treatment of a hypocholinergic disorder, which comprises treating a patient in need of said treatment with an effective dose of a N-methyl-D-aspartate receptor antagonist Component (a) selected from the group consisting of memantine and pharmaceutical acceptable salts thereof and with an effective amount of a naAEA Component (b), in further combination with

(c) donepezil or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 10 mg to 92 mg of donepezil hydrochloride and;

(d) solifenacin or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate.

7. The method of claim 6, wherein said effective amount of memantine or a pharmaceutically acceptable salt thereof Component (a), is a daily dose that is equivalent to from 5 mg to 30 mg of memantine hydrochloride.

8. The method of claim 6, wherein

said Component (a) is a pharmaceutical composition in dosage unit form comprising said memantine or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier or vehicle;

said Component (b) is a pharmaceutical composition in dosage unit form comprising a naAEA selected from the group consisting of alosetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in alosetron) of from 0.25 mg to 6 mg;

azasetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in azasetron) of from 5 mg to 60 mg;

dolasetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in dolasetron) of from 25 mg to 600 mg;

granisetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in granisetron) of from 0.5 mg to 6 mg;

ondansetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in ondansetron) of from 2 mg to 64 mg;

palonosetron and pharmaceutically acceptable salts and solvated thereof, in an amount (in palonosetron) of from 0.25 mg to 3 mg;

ramosetron and pharmaceutically acceptable salts and solvates thereof, in an amount (in ramosetron) of from 0.0125 mg to 0.3 mg;

tropisetron and pharmaceutically acceptable salts and solvates thereof, in an amount of from 2.5 mg to 30 mg;

domperidone and pharmaceutically acceptable salts and solvates thereof, in an amount (in domperidone) of from 5 mg to 60 mg;

haloperidol, in an amount of from 0.5 mg to 60 mg;

chlorpromazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in chlorpromazine) of from 12.5 mg to 600 mg;

prochlorperazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in prochlorperazine) of from 2.5 mg to 30 mg;

metoclopramide and pharmaceutically acceptable salts and solvates thereof, in an amount (in metoclopramide) of from 5 mg to 60 mg;

bromopride and pharmaceutically acceptable salts and solvates thereof, in an amount (in bromopride) of from 5 mg to 60 mg;

clebopride and pharmaceutically acceptable salts and solvates thereof, in an amount (in clebopride) of from 0.25 mg to 3 mg;

levosulpiride, in an amount of from 12.5 mg to 600 mg;

alizapride and pharmaceutically acceptable salts thereof, in an amount (in alizapride) of from 25 mg to 300 mg;

trimethobenzamide and pharmaceutically acceptable salts thereof, in an amount (in trimethobenzamide) of from 50 mg to 600 mg;

meclizine (also called meclozine) and pharmaceutically acceptable salts and solvates thereof, in an amount (in meclizine) of from 6.25 mg to 300 mg;

promethazine and pharmaceutically acceptable salts and solvates thereof, in an amount (in promethazine) of from 12.5 mg to 150 mg;

dronabinol in an amount of from 1.25 mg to 60 mg;

nabilone, in an amount of from 0.5 mg to 6 mg;

aprepitant, in an amount of from 20 mg to 750 mg;

netupitant, in an amount of from 150 mg to 1800 mg;

rolapitant, in an amount of from 30 mg to 360 mg; and

casopitant, in an amount of from 25 mg to 300 mg, in admixture with a pharmaceutical carrier or vehicle;

said Component (c) is a pharmaceutical composition in dosage unit form comprising donepezil or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 20 mg to 92 mg of donepezil hydrochloride, in admixture with a pharmaceutical carrier; and

said Component (d) is a pharmaceutical composition in dosage unit form comprising solifenacin or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition comprising said solifenacin or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate, in admixture with a pharmaceutical or vehicle..

9. The method of claim 8, wherein

said Component (a) is a pharmaceutical composition comprising said memantine hydrochloride in an amount of from 7 mg to 28 mg, in admixture with a pharmaceutical carrier in an ER formulation;

and

said Components (c) and (d) are in a fixed-dose (c/d) combination consisting of a pharmaceutical composition in dosage unit form comprising

(c) donepezil hydrochloride, in an amount of from 10 mg to 92 mg; and

(d) solifenacin succinate, in a pharmaceutical composition comprising said solifenacin succinate in an amount of from 10 mg to 30 mg,

in admixture with a pharmaceutical carrier or vehicle, in an IR-formulation.

10. The method of claim 9 wherein , in said fixed-dose combination (c/d) said Component (c) is donepezil hydrochloride, in an amount of from 10 mg to 50 mg;

and said Component (d) is solifenacin succinate, in an amount of 15 mg.

11. A pharmaceutical combination comprising, as Components,

(a) memantine or a pharmaceutically acceptable salt thereof;

and

(b) solifenacin or a pharmaceutically acceptable salt thereof.

12. The combination of claim 11, wherein said memantine or a pharmaceutically acceptable salt thereof [Component (a)] is in a pharmaceutical composition in dosage unit form, in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier;

and said solifenacin or pharmaceutically acceptable salt thereof [Component (b)] is in a pharmaceutical composition in dosage unit form, in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate, in admixture with a pharmaceutical carrier.

13. The combination of claim 11, wherein said combination is a fixed-dose combination essentially consisting of a pharmaceutical composition comprising

memantine or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride;

and

(b) solifenacin or a pharmaceutical acceptable salt thereof, in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate,

in admixture with a pharmaceutical carrier or vehicle.

14. A pharmaceutical combination comprising

(a) memantine or a pharmaceutically acceptable salt thereof;

and

(b) solifenacin or a pharmaceutically acceptable salt thereof,

for use for treating Alzheimer type dementia in further combination with donepezil or a pharmaceutically acceptable salt thereof.

15. The combination of claim 14 wherein, in said combination, memantine or pharmaceutically acceptable salt is in a pharmaceutical composition comprising said memantine or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier or vehicle;

and said solifenacin or pharmaceutically acceptable salt thereof is in a pharmaceutical composition comprising said solifenacin or pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate, in admixture with a pharmaceutical carrier or vehicle.

16. The combination of claim 14, wherein said memantine or pharmaceutically acceptable salt thereof and said solifenacin or pharmaceutically acceptable salt thereof are in a fixed-dose combination essentially consisting of a pharmaceutical composition comprising said memantine or pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 5 mg to 30 mg;

and said solifenacin or pharmaceutically acceptable salt, in an amount that is equivalent to from 10 to 30 mg, in admixture with a pharmaceutical carrier or vehicle.

17. A method for the treatment of Alzheimer type dementia which comprises treating a patient in need of said treatment with an effective amount of a N-methyl-D-aspartate receptor antagonist selected from the group consisting of memantine and pharmaceutical acceptable salts thereof (Component (a)), and with an effective amount of a non-selective peripheral anticholinergic agent selected from the group consisting of solifenacin and pharmaceutically acceptable salts thereof (Component (b)), in combination with a cholinesterase inhibitor selected from the group consisting of donepezil and pharmaceutically acceptable salts thereof (Component (c)), at a daily dose that is equivalent to from 20 mg to 92 mg of donepezil hydrochloride.

18. The method of claim 17, wherein said Component (a) is memantine or a pharmaceutically acceptable salt thereof, at a daily dose that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, and said Component (b) is solifenacin or a pharmaceutically acceptable salt thereof, at a daily dose that is equivalent to from 10 mg to 30 mg of solifenacin succinate.

19. The method of claim 17, wherein said Component (a) is memantine or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition comprising said memantine or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier or vehicle;

said Component (b) is solifenacin or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition comprising said solifenacin or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 10 mg to 30 mg of solifenacin succinate; and

said Component (c) is donepezil or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition comprising said donepezil or pharmaceutically acceptable salt thereof in an amount that is equivalent to from 20 mg to 92 mg of donepezil hydrochloride.

20. The method of claim 17, wherein said Component (a) is memantine hydrochloride, in a pharmaceutical composition comprising said memantine hydrochloride in an amount of from 7 mg to 28 mg, in admixture with a pharmaceutical carrier in an extended-release formulation;

and said Component (b) is solifenacin succinate, in a pharmaceutical composition comprising said solifenacin succinate in an amount of from 10 mg to 30 mg, in admixture with a pharmaceutical carrier or vehicle in an immediate-release formulation.

21. The method of claim 17 wherein said Component (a) is memantine hydrochloride, in a pharmaceutical composition comprising said memantine hydrochloride in an amount of from 5 mg to 10 mg, in admixture with a pharmaceutical carrier in an immediate-release formulation;

and said Component (b) is solifenacin succinate, in a pharmaceutical composition comprising said solifenacin succinate in an amount of from 10 mg to 30 mg, in admixture with a pharmaceutical carrier or vehicle in an immediate-release formulation.

22. The method of claim 17 wherein said Component (a) is memantine hydrochloride, in a pharmaceutical composition comprising said memantine hydrochloride in an amount of from 5 mg to 10 mg, in admixture with a pharmaceutical carrier in an immediate-release formulation;

said Component (b) is solifenacin succinate, in a pharmaceutical composition comprising said solifenacin succinate in an amount of from 10 mg to 30 mg, in admixture with a pharmaceutical carrier or vehicle in an immediate release formulation, and said Component (c) is donepezil hydrochloride, in a pharmaceutical composition comprising said donepezil hydrochloride, in an amount of from 20 mg to 70 mg, in admixture with a pharmaceutical carrier or vehicle.

23. The method of claim 17 wherein said Component (a) and said Component (b) are in a fixed-dose combination consisting of a pharmaceutical composition comprising memantine or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 5 mg to 30 mg of memantine hydrochloride, in admixture with a pharmaceutical carrier or vehicle as Component (a);

and solifenacin or a pharmaceutically acceptable salt thereof, in an amount that is equivalent to from 5 mg to 30 mg of solifenacin succinate as Component (b), in admixture with a pharmaceutical carrier or vehicle.

24. The method of claim 17, wherein said combination is included in a kit.

25. A pharmaceutical composition in dosage unit form, which comprises (a) memantine hydrochloride, in an amount of from 5 mg to 30 mg;

and (b) solifenacin succinate, in an amount of from 10 mg to 30 mg, in admixture with a pharmaceutical carrier or vehicle.

26. A pharmaceutical unit form comprising (a) memantine hydrochloride, in a pharmaceutical composition comprising said memantine hydrochloride in an amount of from 5 mg to 30 mg, in admixture with a pharmaceutical carrier in extended-release formulation;

and (b) solifenacin succinate, in a pharmaceutical composition comprising said solifenacin succinate in an amount of from 10 mg to 30 mg, in admixture with a pharmaceutical carrier or vehicle in an immediate release formulation.