Uses for quaternary ammonium anticholinergic muscarinic receptor antagonists in patients being treated for cognitive impairment or acute delirium

• US 8,097,633 B2
• Filed: 11/06/2007
• Issued: 01/17/2012
• 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): Padmanabhan, Sreeni
• Assistant Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US11/935,483
• Publication Number:
  US 20080114014A1
• Time in Patent Office: 1,533 Days
• Field of Search: 514/278, 514/424
• US Class Current: 514/278
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• 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

A method for treating the adverse effects of acetyl-cholinesterase inhibitors used in the treatment of cognitive disorders such as acute delirium and cognitive impairment in elderly human patients. The administration of a clinically effective amount of a quaternary ammonium anti-cholinergic muscarinic receptor antagonist having very low lipid solubility substantially eliminates the adverse effects of urinary and/or fecal incontinence, nausea, bradycardia, bronchorrhea or brochospasm caused by the acetyl-cholinesterase inhibitors, without affecting the beneficial activity of the acetyl-cholinesterase inhibitors. This permits the administration of the optimum effective dosing of acetyl-cholinesterase inhibitors to provide maximum benefit to the patient with the added benefit of reducing or eliminating the unwanted side effects of fecal and urinary incontinence. Further, the combination of rivastigmine and glycopyrrolate has been effective in significantly improving cognitive function in patients suffering from acute dementia or cognitive impairment.

Claims

1. A method to inhibit undesired side effects of acetyl cholinesterase inhibitors used to treat a patient suffering from a cognitive disorder selected from the group consisting of acute delirium and cognitive impairment comprising administering to the patient a therapeutic amount of a quaternary ammonium anti-cholinergic muscarinic receptor antagonist.

2. The method of claim 1 wherein the quaternary ammonium anti-cholinergic muscarinic receptor antagonist exhibits low lipophilicity.

3. The method of claim 1 wherein the quaternary ammonium anti-cholinergic muscarinic receptor antagonist is selected from the group consisting of trospium and glycopyrrolate.

4. The method of claim 1 wherein a therapeutically efficacious amount of the quaternary ammonium anti-cholinergic muscarinic receptor antagonist is administered to the patient.

5. The method of claim 1 wherein the acetyl-cholinesterase inhibitors are selected from the group consisting of donepezil, rivastigmine, galantamine, tacrine, physostigmine, pyridostigmine and neostigmine.

6. The method of claim 1 wherein the quaternary ammonium anti-cholinergic muscarinic receptor antagonist is glycopyrrolate.

7. The method of claim 6 comprising administering from about 0.1 to about 0.8 mg/day parenterally, or about 3.0 to about 8.0 mg/day orally of glycopyrrolate.

8. The method of claim 1, wherein the acetyl-cholinesterase inhibitor is rivastigmine.

9. The method of claim 1, wherein the undesired side effects comprise urinary and fecal incontinence.

15. The method of claim 8, comprising administering about 24 mg/day orally or about 17.4 mg/day transdermally of rivastigmine.

10. A method to inhibit undesired side effects of rivastigmine used to treat a patient suffering from a cognitive disorder selected from the group consisting of acute delirium and cognitive impairment comprising administering to the patient a therapeutic amount of glycopyrrolate.

11. The method of claim 10 wherein a therapeutically efficacious amount of the quaternary ammonium anti-cholinergic muscarinic receptor antagonist is administered to the patient.

12. The method of claim 10 comprising administering from about 1.5 to about 24 mg/day orally, or about 4.6 to about 17.4 mg/day by transdermal patch of rivastigmine.

13. The method of claim 10 comprising administering from about 0.1 to about 0.8 mg/day parenterally, or about 3.0 to about 8.0 mg/day orally of glycopyrrolate.

14. The method of claim 10 comprising administering the combination of from about 1.5 to about 24 mg/day, orally, or about 4.6 to about 17.4 mg/day transdermally of rivastigmine and from about 0.1 to about 0.8 mg/day, parenterally, or about 3 to about 8 mg/day, orally, of glycopyrrolate.

16. The method of claim 10, comprising administering about 24 mg/day orally or about 17.4 mg/day transdermally of rivastigmine.