Method and composition for treating alzheimer-type dementia

• US 9,278,092 B2
• Filed: 09/18/2014
• Issued: 03/08/2016
• Est. Priority Date: 09/18/2009
• Status: Active Grant

• Current Assignee: Chase Pharmaceuticals Corp. (Abbvie Incorporated)
• Original Assignee: Chase Pharmaceuticals Corp. (Abbvie Incorporated)
• Inventors: Chase, Thomas N., Clarence-Smith, Kathleen E.
• Primary Examiner(s): Ivanova, Svetlana M
• Application Number:
  US14/489,827
• Publication Number:
  US 20150005292A1
• Time in Patent Office: 537 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• 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 31/4965 Non-condensed pyrazines
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0056 : Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/2018 : Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/205 : Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 : Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 : Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 1/08 : for nausea, cinetosis or vertigo; Antiemetics
• 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
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

There is described a method for increasing the maximal tolerated close and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-anticholinergic antiemetic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-anticholinergic antiemetic agent for the preparation of a pharmaceutical composition for the treatment of Alzheimer type dementia in combination with an acetyl choline esterase inhibitor (AChEI) and pharmaceutical compositions comprising (a) a 5HT₃ receptor antagonist, a dopamine antagonist, a H1-receptor antagonist, a cannabinoid agonist, aprepitant or casopitant as an antiemetic agent and (b) an acetylcholine esterase inhibitor are also described.

Claims

1. A composition comprising an acetyl choline esterase inhibitor (AChEI) selected from the group consisting of tacrine, donepezil, rivastigmine, galantamine, and pharmaceutically acceptable salts thereof and a non-anticholinergic antiemetic agent, said AChEI being present at a level from 1.1 to 4 times greater than a recommended maximal dose level approved by the U.S. FDA.

2. The composition of claim 1, wherein said non-anticholinergic antiemetic agent is selected from the group consisting of the following anticholinergic antiemetic agent:

5-HT3 receptor antagonists, dopamine antagonists, H1 histamine receptor antagonists, NK1 receptor antagonists and cannabinoid agonists.

3. The composition of claim 2, wherein said 5-HT3 receptor antagonist is selected from group consisting of ondansetron, the pharmaceutically acceptable salts and solvates of ondansetron, granisetron, the pharmaceutically acceptable salts and solvates of granisetron, tropisetron, the pharmaceutically acceptable salts and solvates of tropisetron, lerisetron, the pharmaceutically acceptable salts and solvates of lerisetron, ramosetron and the pharmaceutically acceptable salts and solvates of ramosetron.

4. The composition of claim 2, wherein said dopamine antagonist is selected from group consisting of domperidone, the pharmaceutically acceptable salts and solvates of domperidone, metoclopramide, the pharmaceutically acceptable salts and solvates of metoclopramide, bromopride, the pharmaceutically acceptable salts of bromopride, clebopride, the pharmaceutically acceptable salts of clebopride, alizapride and the pharmaceutically acceptable salts of alizapride.

5. The composition of claim 2, wherein said HI histamine receptor antagonist is meclizine or a pharmaceutically acceptable salt or solvate thereof.

6. The composition of claim 2, wherein said cannabinoid agonist is dronabinol or nabilone.

7. The composition of claim 2, wherein said NK1 receptor antagonist is aprepitant or casopitant.

8. The composition of claim 1 wherein said AChEI is selected from the group consisting of donepezil, rivastigmine, galantamine, and pharmaceutically acceptable salts thereof.

9. The composition of claim 1, wherein said non-anticholinergic antiemetic agent is a 5-HT3 receptor antagonist;

and said AChEI is selected from the group consisting of donepezil and pharmaceutically acceptable salts thereof.

10. The composition of claim 9, wherein said 5-HT3 receptor antagonist is selected from the group consisting of ondansetron, the pharmaceutically acceptable salts and solvates of ondansetron, granisetron, the pharmaceutically acceptable salts and solvates of granisetron, tropisetron, the pharmaceutically acceptable salts and solvates of tropisetron, lerisetron, the pharmaceutically acceptable salts and solvates of lerisetron, ramosetron and the pharmaceutically acceptable salts and solvates of ramosetron.

11. A composition comprising an acetyl choline esterase inhibitor (AChEI) selected from the group consisting of donepezil and pharmaceutically acceptable salts thereof and a non-anticholinergic antiemetic agent consisting of a 5-HT3 receptor antagonist selected from the group consisting of granisetron and pharmaceutically acceptable salts and solvates thereof, said AChEI being present at a level from 1.1 to 4 times greater than a recommended maximal dose level approved by the U.S. FDA.

12. The composition of claim 11, wherein said 5-HT3 receptor antagonist is administered at a daily dose, in granisetron, of from 1 mg to 6 mg.

13. The composition of claim 12, wherein said AChEI is administered orally or parenterally.

14. The composition of claim 12, wherein said combination is orally administered in an IR dosage unit form comprising from 0.5 mg to 3 mg of said 5-HT3 receptor antagonist and from 15 mg to 30 mg of said AChEI, in admixture with a pharmaceutical carrier.