HPBCD Isomer Purification for Selective Cholesterol Chelation
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Solution Overview
Problem
The commercially available mixture of hydroxypropyl-beta-cyclodextrin (HPBCD) lacks specificity in solubilizing or delivering guest molecules due to its uncontrolled alkylation process, leading to a wide range of isomeric configurations, making it difficult to selectively target specific environments or organs.
Innovation Solution
The isolation and use of specific isomers of HPBCD with controlled alkylation patterns, such as DS-6 to DS-14, which are purified through nanofiltration and adjusted to a pH of 6.0 to 7.9, allowing for precise solubilization or chelation of guest molecules like cholesterol.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If uncontrolled alkylation process is used to manufacture HPBCD on large scale, then productivity is improved, but manufacturing precision deteriorates due to wide range of isomeric configurations
Solution Approach 1:
The patent segments the complex mixture of HPBCD isomers into distinct fractions based on their alkylation degree (DS values). By using nanofiltration membranes with specific pore sizes, the process separates molecules into groups (e.g., DS-6 to DS-14), transforming an uncontrolled mixture into defined compositional ranges that maintain productivity while improving precision.
Solution Approach 2:
The patent changes the physical-chemical parameters of the separation process by using nanofiltration under controlled pH conditions (pH 6.0 to 7.9). This parameter control enables selective passage of specific isomer groups through the membrane, achieving precision in isomeric configuration while maintaining industrial-scale productivity.
2Ease of manufacture
If gross mixture of HPBCD isomers is used, then ease of manufacture is improved, but reliability deteriorates due to inability to selectively solubilize or deliver specific guest molecules
Solution Approach 1:
The patent divides the HPBCD mixture into segments with specific DS ranges (e.g., DS-6 to DS-14). Each segment has distinct solubilization properties that enable selective interaction with specific guest molecules, thereby improving reliability while maintaining manufacturing simplicity through the nanofiltration process.
Solution Approach 2:
The patent assigns different functional qualities to different isomer groups based on their DS values. Specific DS ranges are optimized for specific applications (e.g., cholesterol solubilization), creating local quality variations that enhance selective delivery capability while keeping the overall manufacturing process simple.
3Reliability
If specific isomers of HPBCD are isolated and purified, then reliability is improved for selective guest molecule delivery, but device complexity increases due to additional purification steps
Solution Approach 1:
The patent introduces nanofiltration membranes as intermediary elements that facilitate the separation of HPBCD isomers. These membranes act as mediators between the crude mixture and the purified fractions, enabling reliable selective delivery capability while keeping the purification process relatively simple through a single-pass nanofiltration step.
Solution Approach 2:
The patent controls pH parameters (maintaining pH 6.0 to 7.9) during the nanofiltration process to optimize the separation efficiency. This parameter control enhances reliability of isomer isolation without significantly increasing process complexity, as it involves simple pH adjustment rather than multiple complex purification steps.
4Manufacturing precision
If nanofiltration is used to purify HPBCD isomers, then manufacturing precision is improved, but use of energy increases due to additional processing requirements
Solution Approach 1:
The nanofiltration membrane serves as an energy-efficient intermediary that separates isomers based on size and charge differences without requiring high energy input. Unlike chromatography or distillation methods, nanofiltration achieves precise isomer separation with minimal energy consumption, maintaining manufacturing precision while reducing energy use.
Solution Approach 2:
The patent uses hydraulic pressure-driven nanofiltration to achieve isomer separation. This hydraulic approach is more energy-efficient than thermal methods, as it utilizes pressure differentials rather than heat energy to drive the separation process, thereby reducing overall energy consumption while maintaining high precision.
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 conditions like Niemann-Pick disease Type C, liver disease, cardiovascular disease, and familial hypercholesterolemia by selectively delivering and releasing the guest molecule.
Implementation Method 1
The mixture may be further purified by nanofiltration as described in U.S. Pat. No. 11,958,917, the entire content of which is incorporated by reference herein.
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.