Nicotine Pulsatile Dosage for Parkinson's Gait and Balance
Solution Overview
Problem
Current treatments for Parkinson's Disease, particularly those involving dopaminergic agents like levodopa, often become ineffective as the disease progresses and can cause side effects such as dyskinesia, necessitating a need for alternative therapeutic approaches to manage motor symptoms and associated balance and gait issues.
Innovation Solution
A pulsatile or extended release dosage form of nicotine is developed, providing a first and second release peak within specific time frames, and a delayed release formulation using enteric-coated tablets or capsules to maintain effective plasma concentrations of nicotine for an extended period, thereby treating symptoms of Parkinson's Disease and reducing side effects associated with dopaminergic treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dopaminergic agents like levodopa are used to treat Parkinson's Disease, then motor symptoms are managed, but the treatment becomes ineffective as the disease progresses and causes side effects such as dyskinesia
Solution Approach 1:
The patent changes the chemical parameter by using nicotine (a nicotinic receptor agonist) instead of dopaminergic agents. This parameter substitution allows treatment of Parkinson's Disease through a different mechanism of action, potentially avoiding the progression-related ineffectiveness and dyskinesia side effects associated with levodopa and dopamine agonists
2Speed
If standard release formulations are used, then immediate symptom relief is achieved, but plasma concentrations fluctuate causing dyskinesia and treatment ineffectiveness
Solution Approach 1:
The patent segments the nicotine dosage into multiple formulations with different release characteristics (immediate release, extended release, pulsatile release). This segmentation allows different portions of the dosage to provide different functions: immediate release for rapid onset and extended/pulsatile release for maintaining stable plasma concentrations over time
Solution Approach 2:
The patent employs pulsatile release formulations that deliver nicotine in periodic bursts rather than continuous release. This periodic action maintains plasma concentrations within the therapeutic window (0.5-5 ng/mL) by providing regular dosing peaks, preventing both subtherapeutic periods and toxic peaks that cause dyskinesia
3Reliability
If frequent dosing is administered to maintain therapeutic levels, then symptom control is improved, but patient compliance decreases and treatment complexity increases
Solution Approach 1:
The patent uses extended release formulations that maintain continuous therapeutic levels of nicotine in the plasma over extended periods (24 hours or more). This continuity eliminates the need for frequent dosing while maintaining reliable symptom control, as the drug is released slowly and steadily to keep plasma concentrations within the therapeutic window without requiring multiple daily administrations
Data Source
AI summary
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.