Combined acetylcholinesterase inhibitor and quaternary ammonium antimuscarinic therapy to alter progression of cognitive diseases

• US 8,969,402 B2
• Filed: 02/27/2013
• Issued: 03/03/2015
• Est. Priority Date: 11/15/2006
• Status: Active Grant

• Current Assignee: Qaam Pharmaceuticals, LLC
• Original Assignee: Steven A. Rich
• Inventors: Rich, Steven A.
• Primary Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US13/778,530
• Publication Number:
  US 20130172379A1
• Time in Patent Office: 734 Days
• Field of Search: 514/424, 514/319
• US Class Current: 514/424
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/20 having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
• CPC Class Codes: A61K 31/201 having one or two double bonds, e.g. oleic, linoleic acids
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• 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 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 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms
• CPC Class Codes: C07D 451/00 Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof

Abstract

A method administers quaternary ammonium anti-cholinergic muscarinic receptor antagonists in combination with acetyl-cholinesterase inhibitors to treat either cognitive impairment or acute delirium. This therapy results in a modification of a cognitive disorder or disease, namely a slow down in the disease progression. In one preferred embodiment, the disease is dementia with Lewy Bodies. New formulations for quaternary ammonium anti-cholinergic muscarinic receptor antagonists are also disclosed.

Claims

1. A method for altering a disease progression of dementia with Lewy Bodies comprising administering to a patient a therapeutic amount of glycopyrrolate and a therapeutic amount of rivastigmine.

2. The method of claim 1, wherein the disease progression is altered by slowing the progression of dementia with Lowy Bodies compared to disease progression in patients am treated with glycopyrrolate and rivastigmine.

3. A method for altering a disease progression of a cognitive disorder selected from the group consisting of Alzheimer'"'"'s Disease, Dementia with Lewy Bodies, Parkinson'"'"'s Disease, Fronto-temporal dementia, and Progressive Supranuclear Palsy, comprising administering to a patient a therapeutic amount of glycopyrrolate and a therapeutic amount of rivastigmine.

4. The method of claim 3, wherein the disease progression is altered by slowing the progression of the disease compared to disease progression in patients not treated with rivastigmine and glycopyrrolate.

5. The method of claim 3, comprising administering a minimum of about 2-4 mg/day of glycopyrrolate and a minimum of about 12-48 mg/day of rivastigmine to the patient.

6. The method of claim 3, comprising administering a minimum of about 12 mg/day orally or a minimum of about 9.5 mg/day transdermally of rivastigmine to the patient.

7. The method of claim 3, comprising administering between about 24 and about 48 mg/day orally or administering between about 19 mg and 54 mg transdermally of rivastigmine to the patient.

8. The method of claim 3, wherein an efficacious therapeutic amount of glycopyrrolate is administered to the patient either orally, intravenously or parenterally.

9. The method of claim 3, wherein the therapeutic amount of rivastigmine is administered to the patient either orally or transdermally.