Acyclic CB[n] Molecular Containers for Drug Solubility
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Solution Overview
Problem
Many drug candidates fail to reach pharmacy shelves due to poor aqueous solubility, leading to low bioavailability, as existing solubility enhancement methods like cyclodextrin-based solutions are not universal and do not effectively address the issue of poor bioavailability for all drug candidates.
Innovation Solution
Development of acyclic CB[n]-type compounds that form non-covalent complexes with pharmaceutical agents, enhancing their solubility in aqueous solutions and improving bioavailability, with solubilizing groups such as sulfonic acid and polyethylene glycol, and targeting groups for specific delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cyclodextrin-based solubility enhancement is used, then solubility of some drugs is improved, but it is not a universal solution and fails for many drug candidates
Solution Approach 1:
The patent develops calixarene-based molecular containers with multiple functional groups (sulfonic acid, carboxylic acid, hydroxyl, amine) that can interact with diverse pharmaceutical agents through various mechanisms (ion-dipole, hydrogen bonding, hydrophobic interactions), making the solubility enhancement method universally applicable to different drug classes including basic drugs, acidic drugs, and neutral drugs, unlike cyclodextrins which are limited to specific drug types
Solution Approach 2:
The calixarene molecules are designed with specific functional groups positioned at different locations (upper rim, lower rim, sidewalls) to create distinct interaction zones that can simultaneously accommodate different types of pharmaceutical agents with varying chemical properties, enabling broad-spectrum solubility enhancement
2Reliability
If high potency drug candidates are selected, then therapeutic efficacy is improved, but poor aqueous solubility leads to low bioavailability and abandonment
Solution Approach 1:
The calixarene-based molecular containers act as intermediaries between high-potency but poorly soluble drug candidates and the aqueous environment, forming non-covalent inclusion complexes that enhance solubility up to 2750-fold while maintaining drug stability and bioavailability, thereby enabling the clinical use of high-potency compounds that would otherwise be abandoned
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 acyclic CB[n]-type compounds significantly enhance the solubility of pharmaceutical agents, improving their bioavailability and therapeutic efficacy, as demonstrated by increased solubility enhancements of up to 2750-fold for various drugs, and show non-toxicity to human cells and tissues.
Implementation Method 1
compounds having the following structure: where each R is independently hydrogen, C1 to C20 alkyl group, C3 to C20 carbocyclic group, C1 to C20 heterocyclic group, carboxylic acid group, ester group, amide group, hydroxy, or ether group. Each is independently a C5 to C20 carbocyclic ring system or C2 to C20 heterocyclic ring system, where the ring system comprises one or more rings.
Implementation Method 2
The present invention provides compounds having the following structure... The present invention also provides compositions comprising a compound of the present invention and a pharmaceutical agent. The pharmaceutical agent can be non-covalently complexed to the compound.
Implementation Method 3
At least one of the ring systems has at least one solubilizing group selected from sulfonic acid, sulfonate salt, phosphonic acid, phosphonate salt, and polyethylene glycol.
Data Source
AI summary
Acyclic CB[n]-type compounds, methods of making such compounds, and uses of the compounds. For example, these compounds can be used as nanocontainers to solubilize pharmaceutical agents. Also provided are compositions and methods of using them for therapy or prophylaxis of a wide variety of conditions for which therapy or prophylaxis is desirable.