Hydroxypropyl-Beta-Cyclodextrin Isomer Control for Cholesterol Affinity
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Solution Overview
Problem
Existing hydroxypropyl-β-cyclodextrin (HPBCD) products are gross mixtures with uncontrolled alkylation, leading to a vast array of isomeric configurations, making selective solubilization or delivery of guest molecules impractical, particularly for applications like treating Niemann-Pick disease Type C, liver disease, cardiovascular disease, and cholesterol deposits.
Innovation Solution
Isolation and use of specific isomers of HPBCD with controlled alkylation patterns, achieving a mixture with defined substitution levels and chemical properties, suitable for intrathecal, intravenous, or intracerebroventricular administration, enhancing selective solubilization and chelation capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If uncontrolled alkylation is used in HPBCD manufacturing, then production cost is reduced and manufacturing simplicity is improved, but product selectivity and solubilization specificity deteriorate
Solution Approach 1:
The patent applies parameter changes by precisely controlling the degree of substitution (DS) to specific ranges (DS 6-9) and controlling the distribution of hydroxypropyl groups at different positions (2-O-, 3-O-, 6-O-positions) on the cyclodextrin ring. This selective parameter control enables the HPBCD to achieve specific solubilization properties for different guest molecules while maintaining a practical manufacturing process
2Adaptability or versatility
If isomeric purification is performed on HPBCD, then solubilization selectivity is improved, but manufacturing complexity and cost increase
Solution Approach 1:
Rather than performing complex isomeric purification, the patent changes the manufacturing parameters to directly produce HPBCD with controlled degree of substitution (DS 6-9) and controlled positional distribution. This approach achieves the desired selectivity at the synthesis stage, avoiding the need for complex downstream purification equipment and processes
3Adaptability or versatility
If broad substitution patterns are present in HPBCD, then manufacturing flexibility is improved, but affinity for specific guest molecules deteriorates
Solution Approach 1:
The patent resolves this contradiction by implementing controlled parameter ranges: degree of substitution (DS) is controlled to 6-9, and the distribution of hydroxypropyl groups at 2-O-, 3-O-, and 6-O-positions is controlled within specific ranges. This controlled flexibility maintains manufacturing adaptability while ensuring reliable affinity for specific guest molecules like cholesterol and vitamin E
Solution Approach 2:
The patent applies local quality by controlling the specific distribution of hydroxypropyl groups at different positions on the cyclodextrin ring structure. By controlling the substitution pattern at 2-O-, 3-O-, and 6-O-positions independently, the patent creates localized chemical environments that enhance specific guest molecule recognition and binding while maintaining overall manufacturing flexibility
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 purified HPBCD isomers exhibit improved affinity for cholesterol, effectively treating or preventing diseases such as Niemann-Pick disease Type C, liver disease, and cardiovascular disease, with enhanced selectivity and reduced side effects.
Implementation Method 1
HPBCD is usually manufactured by subjecting β-cyclodextrin to propylene oxide in the presence of a base in order to alkylate the cyclodextrin ring with hydroxypropyl groups
Implementation Method 2
there may be a need to selectively solubilize or chelate a specific guest molecule that is found within a mixture of many substituents in a solution or suspension such as cholesterol in blood or spinal fluid
Data Source
AI summary
The present disclosure relates to compositions comprising mixtures of hydroxypropyl-β-cyclodextrin, wherein the compositions may be isomerically purified. The disclosure also relates to methods of isomerically purifying a mixture of hydroxypropyl-β-cyclodextrins.