Cross-Linked Polymeric Chelators for Low-Toxicity Iron Removal
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Solution Overview
Problem
Current iron chelation therapies for treating iron overload diseases, such as desferoxamine (DFO), have a narrow therapeutic window, require frequent administration, and cause significant systemic side effects, while orally available chelators like deferiprone and Exjade have adverse effects like neutropenia and hypersensitivity reactions. There is a need for a novel iron chelator that binds iron tightly and removes it from the body with high selectivity and low toxicity.
Innovation Solution
Development of cross-linked polymeric chelators comprising polyamine polymer backbone chains cross-linked with specific molecular weight cross-linkers and coupled with metal chelators, such as 2,3-dihydroxybenzoic acid, to form a composition that can be administered orally or parenterally, selectively binding iron in the gastrointestinal tract or bloodstream.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional iron chelators like desferoxamine are used, then iron binding capacity is achieved, but systemic side effects increase and therapeutic window narrows
Solution Approach 1:
The invention segments the chelation function from systemic circulation by using polymeric chelators that remain confined to the gastrointestinal tract. The polymer structure divides the chelating agents into multiple units attached to a backbone, allowing localized action without systemic distribution. This resolves the contradiction by maintaining iron binding capacity while eliminating systemic side effects through spatial segmentation of the therapeutic action.
Solution Approach 2:
The polymeric structure acts as an intermediary carrier that delivers chelating agents to iron in the gastrointestinal tract without allowing the chelators to enter systemic circulation. The polymer backbone serves as a mediator that binds chelators and targets them to the GI tract, preventing direct contact with systemic tissues and thereby reducing harmful effects while maintaining therapeutic efficacy.
2Reliability
If conventional iron chelators are administered, then iron removal from body is achieved, but administration frequency increases and treatment complexity increases
Solution Approach 1:
The invention merges multiple chelating agent units onto a single polymeric backbone structure, creating a multi-functional chelator that can bind multiple iron ions simultaneously. This combining of chelating functions into one administered unit increases iron removal efficacy per dose and reduces the frequency of administration needed, resolving the contradiction between treatment effectiveness and time loss from frequent dosing.
3Object-affected harmful factors
If oral iron chelators are used, then systemic side effects are reduced, but iron binding affinity may decrease
Solution Approach 1:
The invention creates a composite polymeric structure that combines chelating agent units with a polymer backbone, achieving both high iron binding affinity and oral safety. The composite structure allows the chelators to maintain their affinity for iron while the polymeric framework prevents systemic absorption. This resolves the contradiction by integrating two functional requirements into a single composite material that delivers both high affinity binding and localized action.
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 polymeric chelators demonstrate high iron binding affinity and selectivity, reducing systemic side effects and improving treatment efficacy by preventing iron absorption into the bloodstream, with potential for oral administration and extended circulation half-life.
Implementation Method 1
polymeric chelators that selectively sequester and remove excess dietary iron from the GI tract by binding iron to form nontoxic, inert complexes
Data Source
AI summary
Compositions comprising a polymeric chelator comprising a plurality of polyamine polymer backbone chains and one or more chelators covalently coupled thereto, wherein the plurality of polyamine polymer backbone chains are cross-linked with a plurality of cross-linkers each having a number average molecular weight of 200 Daltons to 6000 Daltons. Also disclosed are methods of making and using the composition, e.g., for removing metal from a medium or treating iron overload disease.