PEG-Modified Metastin Derivative for Cancer and Hormonal Treatment

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Solution Overview

Problem

Current metastin derivatives lack optimal biological activities and stability for effectively suppressing cancer metastasis, controlling pancreatic and placental functions, and promoting gonadotropic hormone secretion, while also addressing various metabolic and reproductive disorders.

Innovation Solution

A metastin derivative modified with polyethylene glycol (PEG), specifically PEG-modified peptides with specific amino acid substitutions, exhibiting improved pharmacokinetics and enhanced LH and testosterone release actions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If metastin is used for suppressing cancer metastasis and controlling physiological functions, then biological activity is achieved, but stability and pharmacokinetics are insufficient

Engineering Contradiction:
Improvebiological activityVSAvoidstability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent applies PEGylation technology to create a composite structure where polyethylene glycol chains are covalently attached to the metastin peptide. This composite material combines the biological activity of metastin with the stability and pharmacokinetic advantages of PEG, resolving the contradiction between biological activity and stability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the physical and chemical parameters of metastin by attaching PEG chains of different molecular weights (PEG5K, PEG20K, PEG40K). This parameter change enhances the stability and pharmacokinetic properties while preserving the biological activity, effectively resolving the contradiction.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If PEG modification is applied to metastin to improve stability, then pharmacokinetics improve, but biological activity may be reduced

Engineering Contradiction:
ImprovestabilityVSAvoidbiological activity
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent employs site-specific PEGylation where PEG chains are attached at specific locations on the metastin peptide structure. This local modification approach preserves the critical regions responsible for biological activity while adding stability through PEG attachment, resolving the contradiction between stability and biological activity.

Inventive Principle:
Principle #3Local quality

3Duration of action of moving object

If sustained release preparations are used for metastin, then duration of action is extended, but manufacturing complexity increases

Engineering Contradiction:
Improveduration of actionVSAvoidmanufacturing complexity
Core Design Contradiction:
Duration of action of moving objectVSEase of manufacture

Solution Approach 1:

The PEG-modified metastin derivatives exhibit self-sustained release properties in the body. The PEG chains provide steric protection and control drug release kinetics without requiring complex external delivery systems, thereby extending duration of action while simplifying manufacturing compared to traditional sustained release formulations.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP2314609B1Metastin derivative and use thereof
Publication Date: 2016.11.30 TAKEDA PHARMA CO LTD
  • EP2314609B1 patent drawingFigure 1A~1B
  • EP2314609B1 patent drawingFigure 2A~2B
  • EP2314609B1 patent drawingFigure 3

AI summary

Disclosed is a stable metastin derivative having excellent biological activities (e.g., a cancer metastasis inhibiting activity, a cancer proliferation inhibiting activity, a gonadotropin secretion promoting activity, a sex hormone secretion promoting activity). A metastin derivative produced by substituting a constituent amino acid in metastin can be improved in stability in the blood and can have an excellent cancer metastasis inhibiting activity, an excellent cancer proliferation inhibiting activity, an excellent gonadotropin secretion inhibiting activity, an excellent sex hormone secretion inhibiting activity and the like by binding the metastin derivative to polyethylene glycol.