Compositions and methods for treatment of symptoms in parkinson's disease patients

• US 10,653,686 B2
• Filed: 07/25/2017
• Issued: 05/19/2020
• Est. Priority Date: 07/06/2011
• Status: Active Grant

• Current Assignee: Tyler Medical Research LLC
• Original Assignee: Parkinson's Institute
• Inventors: Azhir, Arasteh Ari
• Primary Examiner(s): Fubara, Blessing M
• Application Number:
  US15/659,383
• Publication Number:
  US 20190054078A1
• Time in Patent Office: 1,029 Days
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2068 Compounds of unknown constitution, e.g. material from plants or animals oils, fats, waxes, shellac A61K9/2013
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61K 9/4891 Coated capsules; Multilayered drug free capsule shells with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

Abstract

The invention provides dosage forms and methods utilizing nicotine to treat symptoms of a neurologic disorder. In some embodiments, the invention provides compositions for treatment of gait and balance problems associated with Parkinson'"'"'s Disease.

Claims

1. A pulsatile release dosage form for twice-daily administration, said form comprising a capsule comprising an effective amount of nicotine for treatment of symptoms of Parkinson'"'"'s Disease or symptoms associated with dopaminergic treatment of Parkinson'"'"'s Disease, wherein said capsule is configured to exhibit pulsatile release of said nicotine when administered, the pulsatile release comprising a first peak and a second peak, wherein the first peak occurs within about two hours of administration and the second peak occurs between about two hours and about twelve hours after administration, wherein said capsule comprises a powder comprising nicotine for providing the first release peak upon administration to a patient, and a bead comprising nicotine for providing the second release peak.

2. The dosage form according to claim 1, wherein said bead is selected from the group consisting of enteric-coated beads, erodible-matrix beads, wax-coated beads, ethylcellulose-coated beads, silicone elastomer coated beads, and combinations thereof.

3. The dosage form according to claim 1, wherein said capsule comprises a water-swellable polymeric membrane.

4. The dosage form according to claim 3, wherein said water-swellable polymeric membrane ruptures following administration to a patient.

5. The dosage form according to claim 1, wherein the dosage form is configured to reduce gait and balance problems.

6. The dosage form according to claim 1, wherein the dosage form is configured to reduce levodopa-induced dyskinesias.

7. The dosage form according to claim 1, wherein nicotine is present at less than 10 mg.

8. The dosage form according to claim 1, wherein about 1-2 mg nicotine is released in a first release, and about 2-3 mg nicotine is released in a second release.

9. The dosage form of claim 8, wherein said dosage form is capable of being administered so that one or more metabolites of said nicotine achieves a plasma level of about 1 to about 500 ng/ml within four hours of administration.

10. The dosage form according to claim 1, wherein said dosage form further comprises levodopa, carbidopa, or a combination thereof.

11. The dosage form according to claim 1 wherein nicotine is present at about 10 mg.

12. A method of treating gait and balance problems in a subject, comprising administering an oral composition comprising the pulsatile release dosage form of claim 1, wherein the gait and balance problems are direct symptoms of Parkinson'"'"'s Disease.