Palladium Complex Antiangiogenic Effect Without Toxic Side Effects

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Solution Overview

Problem

Current antiangiogenic drugs, such as cisplatin and oxaliplatin, have significant side effects, highlighting the need for new molecules with antiangiogenic properties for treating chronic inflammation, cardiovascular diseases, and ocular diseases associated with angiogenesis.

Innovation Solution

A Palladium complex [Pd(sac)(terpy)]•4H2O, where sac = saccharinate and terpy = 2,2':6',2"-terpyridine, is developed and demonstrated to have antiangiogenic effects using the chorion allantoic membrane (CAM) model, offering a potential treatment for chronic inflammation, cardiovascular diseases, and ocular diseases like rheumatoid arthritis, atherosclerosis, and diabetic retinopathy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If platinum-based drugs (cisplatin, oxaliplatin) are used for antiangiogenic treatment, then antiangiogenic effect is achieved, but serious side effects occur (kidney failure, bone marrow suppression, nervous system damage)

Engineering Contradiction:
Improveantiangiogenic effectVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the metallic element parameter from platinum to palladium, creating a new class of antiangiogenic agents. The palladium complex [Pd(sac)(terpy)]ClO4 maintains antiangiogenic efficacy while eliminating the severe side effects associated with platinum-based drugs, as demonstrated by the absence of kidney failure, bone marrow suppression, and nervous system damage in experimental models

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a palladium complex with a designed molecular structure that achieves therapeutic effect without the long-term toxic accumulation characteristic of platinum drugs. The compound demonstrates effective antiangiogenic activity with transient action, avoiding persistent organ damage while maintaining treatment efficacy

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Object-affected harmful factors

If new antiangiogenic molecules are developed to replace platinum drugs, then side effects are reduced, but need for validation in vivo models arises

Engineering Contradiction:
Improveside effectsVSAvoidin vivo validation
Core Design Contradiction:
Object-affected harmful factorsVSDifficulty of detecting and measuring

Solution Approach 1:

The patent employs the chick chorioallantoic membrane (CAM) assay as an intermediary in vivo model to validate the antiangiogenic activity of the palladium complex. This model system provides a simplified yet physiologically relevant platform to demonstrate therapeutic effect and safety profile, bridging the gap between in vitro findings and complex mammalian systems

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent uses the CAM model as a simplified copy of mammalian angiogenesis and vasculature. This model replicates key angiogenic processes and drug responses in a more manageable system, allowing preliminary validation of antiangiogenic compounds before proceeding to more complex and resource-intensive mammalian studies

Inventive Principle:
Principle #26Copying

Data Source

PatentEP3173083B1In vivo antiangiogenic effect of a palladium complex
Publication Date: 2023.07.05 T C ISTANBUL UNIVERSITESI
  • EP3173083B1 patent drawingFigure 1
  • EP3173083B1 patent drawingFigure 2~4
  • EP3173083B1 patent drawingFigure 5~6

AI summary

The present invention, is related to newly determined antiangiogenic effect of a palladium complex [Pd(sac)(terpy)] (sac)•4H2O (sac=saccharinate and terpy=2,2':6',2"-terpyridine)] apart from the antineoplastic effect. The present invention in another aspect, is related to use of the aforementioned Palladium complex in treatment of diseases in which angiogenesis is effective, especially in treatment of chronic inflammation, cardiovascular diseases and ocular diseases. More especially, the present invention is related to the use of the palladium complex according to this invention in treatment of the aforementioned diseases which are developed with angiogenesis.