Metal-Salen Complex Grain Size Control for Magnetic Drug Delivery

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Solution Overview

Problem

Metal-salen complex compounds face challenges in achieving an optimal grain size for capillary passage and magnetic guidance, as sizes too small lack magnetism and sizes too large cannot pass through capillaries, necessitating a controlled grain size for effective drug delivery.

Innovation Solution

The metal-salen complex compound is formulated to have a crystal grain size of 1 µm or less to ensure capillary passage and ferromagnetism, with a preferred range of 100 nm to 500 nm, allowing for targeted delivery and retention with an external magnetic field.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Force

If the grain size of metal-salen complex is increased to enhance magnetic properties, then magnetic guidance capability is improved, but the ability to pass through capillaries deteriorates

Engineering Contradiction:
Improvemagnetic propertiesVSAvoidgrain size
Core Design Contradiction:
ForceVSLength of moving object

Solution Approach 1:

The patent applies parameter changes by precisely controlling the grain size of metal-salen complex particles to fall within the 100 nm to 500 nm range. This specific parameter range simultaneously satisfies two contradictory requirements: it is large enough to exhibit sufficient ferromagnetic properties for magnetic guidance, yet small enough to pass through biological capillaries for systemic delivery to the target site.

Inventive Principle:
Principle #35Parameter changes

2Length of moving object

If the grain size of metal-salen complex is decreased to improve capillary passage, then ability to pass through capillaries is improved, but magnetic properties deteriorate

Engineering Contradiction:
Improvegrain sizeVSAvoidmagnetic properties
Core Design Contradiction:
Length of moving objectVSForce

Solution Approach 1:

The patent resolves this contradiction by establishing a lower bound for grain size at 100 nm. Particles smaller than this would lack sufficient magnetic moment for effective magnetic guidance and retention at the target site. By setting this minimum size threshold while maintaining the upper bound of 500 nm for capillary passage, the patent optimizes both magnetic responsiveness and biodistribution.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If large grain size is used to ensure magnetic guidance, then magnetic retention at target site is improved, but capillary clogging occurs

Engineering Contradiction:
Improvemagnetic retentionVSAvoidcapillary clogging
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent prevents capillary clogging by strictly limiting the maximum grain size to 500 nm, which is smaller than the typical diameter of biological capillaries (5-10 µm). This parameter control ensures that particles can navigate the vascular system without obstruction while still being large enough to exhibit ferromagnetic behavior for reliable magnetic retention at the target site through external magnetic field application.

Inventive Principle:
Principle #35Parameter changes

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

This controlled grain size enables the compound to be effectively guided to and retained at the target site, minimizing adverse reactions and maximizing therapeutic effects while avoiding capillary clogging.

Implementation Method 1

the usability of the metal-salen complex may be further improved if the dynamics of the metal-salen complex can be controlled, such as by inducing the metal-salen complex to be retained in the affected tissue with a magnetic field after local application to the affected tissue

Methodology Applied
Scientific EffectMagnetic field interaction: Magnetic Field

Implementation Method 2

The metal-salen complex compound is auto-magnetic, and is capable of being retained in the affected site with an external magnetic field

Methodology Applied
Scientific EffectFerromagnetism: Ferromagnetism

Data Source

PatentEP2944627B1Nanometersized metal salen complex compounds, their preparation and their use as systemic antitumor agents
Publication Date: 2021.01.27 IHI CORP
  • EP2944627B1 patent drawingFigure 1~2
  • EP2944627B1 patent drawingFigure 3
  • EP2944627B1 patent drawing

AI summary

The present invention provides a metal-salen complex compound of the formula shown below having a controlled grain size that enables the metal-salen complex compound to exert its pharmacological effects as anticancer drug, at a target region, when guided by magnetic fields to the affected tissue. This metal-salen complex compound has a crystal grain size of 8 µm or less, and that is represented by the chemical formula below. N,N'-Bis(salicylidene)ethylenediamine metal M is Fe, Cr, Mn, Co, Ni, Mo, Ru, Rh, Pd, W, Re, Os, Ir, Pt, Nd, Sm, Eu, or Gd.