Palytoxin Extraction from Palythoa Polyps for Leukemia Therapy

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Solution Overview

Problem

Current methods for extracting and using palytoxin for cancer treatment face challenges such as low yield, complex structure, and limited pharmacological treatments, with existing data showing marginal activity on leukemia, necessitating a more efficient and effective method for obtaining and utilizing palytoxin.

Innovation Solution

A method for obtaining pure palytoxin from Palythoa aff. clavata polyps, which live in symbiosis with Symbiodinium dinoflagellates, involving immersion in a polar solvent, decantation, filtration, evaporation, and reversed phase liquid chromatography, allowing for high-yield extraction and effective treatment of leukemia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If palytoxin is extracted from marine organisms using conventional methods, then the toxin can be obtained for research and potential therapy, but the yield is low and the process is complex

Engineering Contradiction:
Improveyield of palytoxin extractionVSAvoidcomplexity of extraction process
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent extracts palytoxin from the marine organism Palythoa aff. clavata through a simplified multi-step process involving solvent immersion, decantation, filtration, evaporation, and chromatography. This extraction approach isolates the active toxin component while removing complex biological matrices, achieving high purity and yield without requiring overly complex equipment or procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The extraction process is divided into distinct sequential steps: (i) immersion in polar solvent, (ii) decantation, (iii) filtration, (iv) evaporation, and (v) reversed phase liquid chromatography. This segmentation allows each step to be optimized independently and simplifies the overall process by breaking down the complex extraction into manageable, standardized operations.

Inventive Principle:
Principle #1Segmentation

2Reliability

If palytoxin is used to treat leukemia, then antitumoral activity is achieved, but the dose must be precisely controlled to avoid toxicity

Engineering Contradiction:
Improveeffectiveness of leukemia treatmentVSAvoidtoxicity at high doses
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent utilizes infinitesimal doses of palytoxin (in the range of 10^-12 to 10^-9 moles per kilogram of body weight) to achieve therapeutic effects while avoiding toxicity. This represents a dramatic parameter change from conventional dosing, exploiting the unique dose-response relationship where extremely low doses produce antitumoral activity without the harmful effects seen at higher concentrations.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies a partial action principle by using doses that are far below the conventional toxic threshold. The infinitesimal dosing regime provides just enough pharmacological activity to target leukemia cells while remaining well below the level that would cause harmful effects on normal tissues, effectively operating in a sub-toxic therapeutic window.

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If existing pharmacological treatments are used for leukemia, then some cancer types are treated, but the activity on leukemia cell lines is marginal

Engineering Contradiction:
Improveantitumoral activity on leukemiaVSAvoideffectiveness across different leukemia types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent demonstrates that palytoxin at infinitesimal doses exhibits broad-spectrum antitumoral activity against multiple types of leukemia cell lines, including both lymphoblastic and myelogenous leukemia. This universal effectiveness across different leukemia subtypes suggests the toxin targets a common mechanism present in various leukemia types, making it a versatile therapeutic agent.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 method achieves a high yield of pure palytoxin, demonstrating strong antitumoral activity on leukemia cell lines, including both lymphoblastic and myelogenous leukemia, with effective treatment at infinitesimal doses, and shows potential for treating various diseases beyond leukemia.

Implementation Method 1

immersion of Palythoa aff. clavata polyps in a polar solvent

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

filtration and/or centrifugation of the liquid obtained from step (ii)

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 3

evaporation of the solvent, preferably by rotary evaporation under reduced air pressure

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 4

evaporation of the solvent, preferably by rotary evaporation under reduced air pressure

Methodology Applied
Scientific EffectVacuum distillation: Vacuum Distillation

Implementation Method 5

purification of the pellet obtained from step (iv), preferably by reversed phase liquid chromatography

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP3087172B1Palytoxyn, its medical use and process for its isolation
Publication Date: 2020.04.01 CORAL BIOME
  • EP3087172B1 patent drawingFigure 1A~2
  • EP3087172B1 patent drawingFigure 3
  • EP3087172B1 patent drawingFigure 4

AI summary

The invention relates to a pharmaceutical composition intended for use in the prevention and/or treatment of leukaemia in a subject, said composition comprising palytoxin (PLTX) and a pharmaceutically acceptable carrier. The application also relates to other medical uses of palytoxin and a method for its extraction from Palythoa clavata polyps. It is also described a method for isolating the symbiodinium dinoflagellate from Palythoa clavata.