Cyclodextrin Derivatives for Uniform Pharmaceutical Composition
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Solution Overview
Problem
Current cyclodextrin-based pharmaceutical compounds, such as Captisol and Sugammadex, are mixtures of positional and regioisomers, making it difficult to define and characterize their compositions, leading to variability in pharmaceutical applications.
Innovation Solution
Development of pure polyanionic and non-ionic cyclodextrin-based compounds with specific negatively charged moieties, counter cations, linkers, bridging groups, and substituents, allowing for well-defined structures and improved characterization, using thioether-linked sulfoalkyl and PEG-ylated linkers to create symmetric cavities for enhanced drug formulations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If chemical modification of cyclodextrins is performed to improve water solubility and pharmaceutical properties, then the pharmaceutical utility is improved, but the product becomes a mixture of positional and regioisomers that are difficult to separate and characterize
Solution Approach 1:
The patent applies local quality by selectively modifying only the primary face (C6 positions) of cyclodextrin molecules, leaving the secondary face unchanged. This localized modification approach ensures that all substitution occurs at identical positions, producing pure polyanionic derivatives without positional or regioisomeric mixtures, thereby achieving both pharmaceutical utility and composition definition
Solution Approach 2:
The patent changes the chemical parameter of the cyclodextrin by introducing negatively charged moieties (such as sulfonate, carboxylate, or phosphate groups) at specific positions. This parameter change transforms neutral cyclodextrins into polyanionic derivatives with improved water solubility and pharmaceutical properties, while maintaining structural uniformity through controlled single-face modification
2Adaptability or versatility
If multiple substitution positions are used to increase functionality, then the versatility is improved, but the complexity of separation and characterization increases
Solution Approach 1:
The patent segments the cyclodextrin modification into two distinct parts: the unchanged secondary face that maintains the hydrophobic cavity and inclusion complexation ability, and the modified primary face that provides water solubility and pharmaceutical functionality through negatively charged groups. This segmentation allows functional diversity without creating complex mixtures requiring separation
Solution Approach 2:
Instead of modifying the secondary face as traditionally done to add functionality, the patent inverts the approach by modifying only the primary face. This inversion simplifies the product structure by concentrating all functional modifications at one location, eliminating regioisomer formation while preserving the essential drug-binding capability of the secondary face
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 resulting compounds provide well-defined, symmetric structures that can bind to other molecules with higher affinity, facilitating the creation of stable drug formulations and excipients with consistent compositions, suitable for pharmaceutical applications.
Implementation Method 1
CDs can be used to form 'inclusion complexes' in which a drug is included and carried within the cavity
Implementation Method 2
Y(+) is one or more counter cations
Data Source
AI summary
The present application provides polyanionic and non-ionic cyclodextrin-based compounds, and methods of manufacturing them. The compounds comprise a negatively-charged or neutral moiety (and, for polyanionic compounds, a suitable counter cation), one or more linkers, optionally one or more bridging groups, a cyclodextrin, and one or more substituents on the cyclodextrin. The compounds can be used in pharmaceutical compositions, and as excipients or carriers of guest molecules.