Alginate Lyase Dissolves Embolic Biomaterials

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Solution Overview

Problem

Current liquid embolic agents for treating cerebral aneurysms, such as alginate-based materials, face challenges including migration, parent artery occlusion, and cytotoxicity, necessitating the development of agents that can selectively dissolve alginate to enhance safety and efficacy in embolization procedures.

Innovation Solution

Administration of an alginate lyase composition, which may include a divalent metal chelator, to specifically dissolve alginate-based biomaterials in subjects, addressing issues like migration and occlusion, and enabling controlled release or delivery of therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If alginate-based liquid embolic agents are used to treat cerebral aneurysms, then aneurysm filling and occlusion are improved, but migration into parent artery and vessel occlusion risks increase

Engineering Contradiction:

Improveaneurysm filling efficacyVSAvoidmigration and vessel occlusion risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces alginate lyase as an intermediary substance that mediates between the alginate embolic agent and the vascular system. The lyase enzyme selectively degrades alginate at the aneurysm site, allowing controlled dissolution of the embolic material to prevent migration while maintaining initial occlusion efficacy. This intermediary mechanism resolves the contradiction by providing a safety valve for the embolic agent.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes changes in the chemical parameters of alginate through enzymatic degradation. By administering alginate lyase, the molecular structure and physical properties of the alginate embolic agent are transformed over time, converting it from a solid occluding mass to a soluble state. This parameter change allows the material to remain stable during injection and occlusion, then become soluble to prevent migration complications.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If alginate hydrogel is injected for embolization, then aneurysm cavity filling is improved, but catheter adhesion and injection complications increase

Engineering Contradiction:

Improveembolization effectivenessVSAvoidcatheter adhesion

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

Alginate lyase acts as a protective intermediary that prevents direct adhesion between the alginate hydrogel and catheter surfaces. The enzyme creates a soluble layer or facilitates controlled degradation at the interface, reducing the adhesive forces that cause catheter sticking and injection complications while preserving the embolization function.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If alginate-based biomaterials are used for embolization, then permanent occlusion is achieved, but cytotoxicity and safety concerns increase

Engineering Contradiction:

Improvepermanent occlusionVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs temporal parameter changes where the alginate embolic agent maintains its occlusive properties initially, then undergoes enzymatic degradation to become biocompatible and non-toxic. The physical and chemical parameters of the material are transformed from a potentially cytotoxic state to a safe, soluble state through controlled lyase-mediated degradation, achieving both permanent occlusion and reduced cytotoxicity.

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

The alginate lyase composition effectively dissolves alginate-based biomaterials, reducing the risk of complications like vessel occlusion and stroke, while allowing for selective delivery and controlled release of therapeutic agents, thereby improving the safety and effectiveness of embolization procedures.

Implementation Method 1

administration of an alginate lyase composition, which may include a divalent metal chelator, to specifically dissolve alginate-based biomaterials

Methodology Applied

Scientific EffectEnzymatic hydrolysis: Hydrolysis

Implementation Method 2

composition comprising an alginate lyase further comprises a divalent metal chelator

Methodology Applied

Scientific EffectChelation:

Data Source

PatentUS9220761B2Alginate and alginate lyase compositions and methods of use

Publication Date: 2015.12.29 JOHNS HOPKINS UNIVERSITY

AI summary

The invention features alginate and alginate lyase compositions and methods that are useful for the treatment of various conditions and diseases. The invention also provides kits and instructions for use.