Benzothiazole Pamoate and Palmitate Salts for Sustained Dopamine Release
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Solution Overview
Problem
Current treatments for Parkinson's disease and restless leg syndrome, such as quick release and sustained release hydrochloride tablets, require frequent administration, leading to compliance issues and fluctuating dopamine levels, which can exacerbate symptoms and increase the risk of aspiration pneumonia due to dysphagia, and there is a need for long-acting sustained release formulations to maintain stable drug concentrations.
Innovation Solution
Development of salts and crystal forms of (S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole, specifically pamoate and palmitate, which exhibit low solubility and enable sustained release formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If quick release hydrochloride tablets are used, then the drug can be administered frequently, but the compliance deteriorates and dopamine levels fluctuate
Solution Approach 1:
The patent changes the chemical form of the drug from hydrochloride salt to pamoate or palmitate salt, which fundamentally alters the release characteristics. This parameter change enables long-acting sustained release over 24 hours, transforming the administration frequency from multiple times daily to once daily, thereby improving compliance while maintaining stable dopamine levels
Solution Approach 2:
The patent creates composite salt compounds by combining the active ingredient with pamoic acid or palmitic acid. These composite salt forms exhibit different solubility and release properties compared to the parent compound, enabling sustained release formulations that improve both administration convenience and patient compliance
2Loss of time
If sustained release hydrochloride tablets are used, then the administration frequency is reduced, but the solubility is insufficient for optimal release
Solution Approach 1:
The patent modifies the salt form parameter to achieve optimal balance between solubility and sustained release. By using pamoate or palmitate salts instead of hydrochloride, the compound maintains adequate solubility for effective release while providing prolonged duration of action, resolving the contradiction between reduced administration frequency and sufficient solubility
3Ease of operation
If frequent administration is required, then the dose can be adjusted, but the compliance deteriorates and adverse effects increase
Solution Approach 1:
The patent achieves continuous and stable dopamine stimulation through long-acting sustained release formulation. The pamoate or palmitate salt forms maintain consistent drug levels in the brain over 24 hours, eliminating the pulsatile stimulation pattern that causes adverse effects, while once-daily administration maintains dose adjustment flexibility through appropriate formulation design
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The salts and crystal forms provide a long-acting sustained release effect, improving patient compliance and reducing the frequency of drug administration while maintaining stable dopamine levels, thereby minimizing adverse effects and the risk of aspiration pneumonia.
Implementation Method 1
The salts or crystal forms of the compound of formula I of present disclosure have a low solubility, which can achieve the sustained release effect
Data Source
AI summary
Provided in the present invention are a salt of a benzothiazole compound as represented by formula I and a crystal form and the use thereof. The salt is selected from pamoate and palmitate. Further provided is the use of the salt of the compound of formula I and the crystal form thereof in the preparation of a drug for treating Parkinson's disease and restless leg syndrome.