Purified HPBCD Isomers for Selective Cholesterol Complexation
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Solution Overview
Problem
The commercially available mixture of hydroxypropyl-beta-cyclodextrin (HPBCD) lacks specificity in solubilizing or chelating guest molecules, leading to non-selective delivery and solubilization, which is inadequate for targeted applications such as treating diseases like Niemann-Pick disease Type C, liver disease, cardiovascular disease, and familial hypercholesterolemia.
Innovation Solution
Isolation and use of specific isomers of HPBCD with controlled substitution patterns, allowing for precise solubilization and chelation, achieved through nanofiltration and pH adjustment to create compositions suitable for intrathecal, intravenous, or intracerebroventricular administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a gross mixture of HPBCD is used, then the solubilization capability is sufficient for general applications, but the selectivity for specific guest molecules is lost
Solution Approach 1:
The patent segments the gross HPBCD mixture into distinct isomeric groups based on substitution patterns (DS-0 through DS-14). By separating molecules with different degrees of substitution and substitution patterns, the invention creates purified compositions that maintain solubilization capability while gaining selectivity for specific guest molecules such as cholesterol.
Solution Approach 2:
The patent extracts specific isomeric components from the gross HPBCD mixture through nanofiltration and other purification methods. By taking out and isolating particular isomers with desired substitution patterns, the invention achieves selective solubilization and chelation capabilities while removing unwanted isomers that would interfere with targeted delivery.
2Reliability
If HPBCD is used for targeted delivery to specific organs, then the therapeutic efficacy is improved, but the gross mixture solubilizes non-desirable spectator molecules as well
Solution Approach 1:
The patent applies local quality by creating HPBCD compositions with specific local molecular characteristics - particular substitution patterns and degrees of substitution at specific hydroxyl positions (2-O-, 3-O-, 6-O-). This local molecular differentiation enables selective interaction with target molecules like cholesterol while avoiding non-specific binding to spectator molecules, thereby improving therapeutic efficacy and reducing off-target effects.
3Ease of manufacture
If the alkylation process is left uncontrolled for industrial scale production, then the manufacturing cost is reduced, but the resulting HPBCD product becomes a complex mixture of 117,655 possible isomeric configurations
Solution Approach 1:
The patent applies preliminary action by performing nanofiltration and purification steps after the uncontrolled alkylation process to separate and isolate specific isomeric groups from the complex mixture. This preliminary purification approach allows industrial-scale production to proceed cost-effectively with uncontrolled alkylation, while subsequent separation steps create the desired pure isomeric compositions for targeted applications.
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 enhanced affinity for cholesterol, effectively treating or preventing diseases like Niemann-Pick disease Type C, liver disease, and cardiovascular disease by selectively delivering therapeutic agents.
Implementation Method 1
achieved through nanofiltration and pH adjustment to create compositions suitable for intrathecal, intravenous, or intracerebroventricular administration
Implementation Method 2
achieved through nanofiltration and pH adjustment to create compositions suitable for intrathecal, intravenous, or intracerebroventricular administration
Implementation Method 3
The purified HPBCD isomers exhibit enhanced affinity for cholesterol, effectively treating or preventing diseases like Niemann-Pick disease Type C
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.