Cycloalkylammonium Benzoate Salt for Stable Ischemic Stroke Injection
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Solution Overview
Problem
Current drugs for treating ischemic cardiovascular and cerebrovascular diseases, such as butylphthalide, face challenges due to poor solubility and stability, leading to low efficacy and the need for combination therapies, limiting their clinical application.
Innovation Solution
Development of cycloalkylammonium 2-(1-hydroxypentyl)benzoate salts with specific cycloalkyl structures and R1 groups, which form stable solid forms suitable for intravenous injection, enhancing solubility and stability, and providing strong anti-platelet aggregation and neuroprotective effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If butylphthalide is used as a lipid-soluble compound to treat ischemic cerebrovascular diseases, then the microcirculation of cerebral ischemic area is improved and angiogenesis is promoted, but the poor solubility in water and low solubility in vivo result in low in vivo utilization and insufficient drug efficacy
Solution Approach 1:
The patent changes the chemical structure parameters of butylphthalide by introducing a carboxylic acid group at the 2-position of the phthalide ring, transforming it from a purely lipid-soluble compound to an amphiphilic compound with improved water solubility while maintaining lipid-soluble characteristics through the phthalide core structure
Solution Approach 2:
The patent creates a composite molecular structure combining the lipid-soluble phthalide core with a water-soluble carboxylic acid group, forming an amphiphilic compound that can utilize both lipid and water pathways for absorption and distribution in the body
2Reliability
If butylphthalide is used to improve cerebral blood flow in ischemic area, then the microcirculation is enhanced, but the compound requires combination with other drugs to enhance effectiveness, limiting its scope of application
Solution Approach 1:
The patent designs the 2-carboxylic acid phthalide compound to possess multiple pharmacological activities including improving microcirculation, promoting angiogenesis, and enhancing cerebral blood flow simultaneously, making a single compound capable of addressing multiple ischemic pathology mechanisms without requiring combination therapies
3Reliability
If existing phthalide derivatives are developed to treat ischemic diseases, then the treatment efficacy is improved, but the preparation process becomes complex and the solid form stability is insufficient for intravenous injection
Solution Approach 1:
The patent segments the molecular structure into a stable phthalide core and a carboxylic acid side group, allowing independent optimization of each component's properties and simplifying the synthesis process by using straightforward coupling reactions between the core and functional group
4Reliability
If butylphthalide is used to treat ischemic cerebrovascular diseases, then the drug provides neuroprotective effects, but the compound exhibits poor stability and requires careful formulation
Solution Approach 1:
The patent modifies the chemical parameters of butylphthalide by introducing a carboxylic acid group that forms stable intramolecular hydrogen bonds and enhances molecular rigidity, thereby improving compound stability while preserving neuroprotective pharmacological activities
Data Source
AI summary
A cycloalkylammonium 2-(1-hydroxypentyl)benzoate salt of the structure represented by formula I, a preparation thereof, a pharmaceutical composition containing the compound as an active ingredient, and a use of the compound in the treatment and/or prevention of ischemic cardiovascular and cerebrovascular disorders, especially mild, moderate and severe acute ischemic strokes.