Platinum Complexes for PEDF Expression and Neuroprotection

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Solution Overview

Problem

Current methods for stabilizing Pigment Epithelial Derived Factor (PEDF) expression in vivo have been ineffective, limiting their use in treating neurological diseases and cancer-related vascularization issues.

Innovation Solution

The use of isolated monomeric platinum complexes, such as cis-diammine-trans-dihydroxo(dihydrogen pyrophosphato)platinum(IV) and 1,2-ethanediamine(dihydrogen pyrophosphato)platinum(II), to increase PEDF gene expression, which are effective in treating neurodegenerative diseases and inhibiting angiogenesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If prior art methods are used to stabilize PEDF expression in vivo, then PEDF expression stability is improved, but the treatment effectiveness for neurological diseases and cancer-related vascularization issues remains insufficient

Engineering Contradiction:
ImprovePEDF expression stabilityVSAvoidtreatment effectiveness
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent employs platinum complexes with specific chemical structures (Pt(II) and Pt(IV) complexes with pyrophosphato ligands) to induce stable PEDF expression. The chemical parameters of the platinum complexes (oxidation state, ligand configuration) are optimized to achieve both stable expression and therapeutic effectiveness, resolving the contradiction between expression stability and treatment reliability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If aggressive cancer treatments are administered, then tumor treatment effectiveness is improved, but neurotoxicity increases

Engineering Contradiction:
Improvetumor treatment effectivenessVSAvoidneurotoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses platinum complexes as intermediary agents that indirectly treat cancer by inducing PEDF expression rather than directly attacking tumor cells. This intermediary approach maintains treatment effectiveness while reducing direct neurotoxicity associated with conventional chemotherapeutic drugs.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the potential harm of chemotherapy-induced neurotoxicity into a benefit by using platinum complexes that stimulate endogenous PEDF production, which then provides neuroprotective effects while maintaining anti-cancer activity.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Quantity of substance

If adenoviral vectors are used for PEDF gene delivery, then PEDF expression is achieved, but inflammatory response and immune rejection occur

Engineering Contradiction:
ImprovePEDF expression levelVSAvoidinflammatory response
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent extracts the gene delivery vector (adenovirus) from the therapeutic approach and replaces it with small molecule platinum complexes. This removal of the viral vector eliminates the source of inflammatory response and immune rejection while maintaining the ability to induce PEDF expression through epigenetic modulation.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP2958568B1Phosphaplatins as neuroprotective agents
Publication Date: 2020.03.04 UNIV HOUSTON SYST
  • EP2958568B1 patent drawingFigure 1
  • EP2958568B1 patent drawingFigure 2A~2F
  • EP2958568B1 patent drawingFigure 3A~3C

AI summary

The present disclosure provides for compositions for the treatment of neurodegenerative diseases comprising one or more isolated phosphate complexes of platinum and methods of uses thereof for treating neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease, stroke, epilepsy, Parkinsons, Huntington's disease and diabetes associated peripheral neuropathy The present disclosure is also directed towards an anti-angiogenic composition useful for inhibiting angiogenesis related to age-related macular degeneration, diabetic retinopathy and tumor-associated angiogenesis. An embodiment of the present disclosure is also directed towards a method for modulating the expression of Pigment Epithelial Derived Factor (PEDF) gene in an individual in need thereof. The present disclosure also provides for a method of reducing neurotoxicity associated with the administration of a cancer therapy in a subject in need thereof comprising administering to the individual in need thereof a therapeutically effective amount of at least one or more isolated monomeric phosphate complexes of platinum described herein.