Lanthanide Metal Phosphate Microspheres for High Loading Capacity
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Solution Overview
Problem
Current holmium-loaded poly-(L)-lactic acid microspheres have a limited holmium loading capacity of around 17 wt.%, which restricts their therapeutic and diagnostic effectiveness, and the use of synthetic organic ligands may pose toxic risks.
Innovation Solution
Preparing microspheres with a lanthanide metal phosphate complex by replacing organic ligands with phosphate in a chimie douce reaction, allowing for higher than 20 wt.% lanthanide content and improved stability, using a method that retains the original microsphere's structure and geometry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If holmium-loaded poly-(L)-lactic acid microspheres are used, then the microspheres can be prepared with a binder stabilizing the structure, but the holmium loading capacity is limited to around 17 wt.%
Solution Approach 1:
The patent changes the chemical composition parameters by replacing the poly-(L)-lactic acid binder with phosphate ligands that form stable complexes with lanthanide metals. This parameter change enables the microspheres to achieve holmium loading capacities exceeding 20 wt.% without requiring traditional binder materials, thus resolving the contradiction between loading capacity and device complexity.
Solution Approach 2:
The patent creates a composite microsphere structure where phosphate complexes with lanthanide metals form the core stabilizing mechanism. This composite approach, combining phosphate ligands with lanthanide ions, replaces the need for separate binder materials while achieving superior loading capacities, effectively resolving the technical contradiction.
2Reliability
If synthetic organic ligands are used to complex with lanthanide metal, then the microspheres can be stabilized, but toxic effects may occur in patients
Solution Approach 1:
The patent replaces complex synthetic organic ligands with simpler phosphate groups that are naturally occurring and biocompatible. This substitution uses a more simple, naturally present chemical group (phosphate) that provides sufficient stabilization without the toxic effects of complex organic ligands, resolving the contradiction between reliability and harmful factors.
Solution Approach 2:
The patent changes the chemical nature of the ligands from synthetic organic compounds to inorganic phosphate groups. This parameter change in ligand type maintains microsphere stability through phosphate-lanthanide complexation while eliminating the toxicity associated with synthetic organic ligands, thus resolving the contradiction.
3Productivity
If high lanthanide content microspheres are prepared with reduced binder material, then the neutron activation time is shortened and specific activity is increased, but the microspheres may disintegrate
Solution Approach 1:
The patent creates a composite structure where phosphate-lanthanide complexes provide both structural stability and high lanthanide content. This composite approach allows the microspheres to maintain structural integrity with reduced binder material, enabling shorter neutron activation times and higher specific activity while preventing disintegration, thus resolving the contradiction between productivity and stability.
Solution Approach 2:
The patent changes the stabilizing mechanism from binder-dependent to complexation-dependent, where phosphate-lanthanide complexation provides structural stability. This parameter change enables high lanthanide content (over 20 wt.%) with minimal binder, achieving both high productivity in neutron activation and maintained structural stability.
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 resulting microspheres have enhanced stability, higher lanthanide content, and improved MRI signals, reducing the amount needed for treatment and diagnosis while minimizing toxicity with naturally occurring ligands.
Implementation Method 1
replacing at least part of the organic ligands in the organic lanthanide metal complex microsphere with phosphate in a chimie douce reaction
Implementation Method 2
the lanthanide metal complex in the resulting microsphere comprises a lanthanide ion and phosphate
Data Source
AI summary
The invention is directed to a method for preparing a microsphere comprising a lanthanide metal phosphate complex, a microsphere, a powder comprising a number of the microspheres, a suspension comprising the microsphere or the powder, the use of the microsphere, a method for detecting a tumour, and a therapeutic composition comprising the microsphere, the powder, or the suspension. The invention provides a method for preparing a microsphere that comprises a lanthanide metal phosphate complex, the method comprising: (a) providing an organic lanthanide metal complex microsphere, wherein the lanthanide metal is present in an amount of more than 20 wt.%, based on total weight of the microspheres, and wherein the organic lanthanide metal complex comprises a lanthanide ion and organic ligands with which the lanthanide ion forms the complex; and thereafter (b) replacing at least part of the organic ligands in the organic lanthanide metal complex microsphere with phosphate in a chimie douce reaction, wherein the lanthanide metal is present in the resulting microsphere in an amount of more than 20 wt.%, based on total weight of the microsphere, and wherein the lanthanide metal complex in the resulting microsphere comprises a lanthanide ion and phosphate.