Self-Degrading Alginate Particles for Controlled Embolization
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Solution Overview
Problem
Existing embolic agents for temporary blood vessel occlusion lack predictable dissolution rates and often cause non-specific occlusions due to unpredictable degradation and migration, requiring additional procedures for dissolution and posing risks to patients.
Innovation Solution
Development of self-degrading alginate particles with controlled degradation properties, achieved by varying molecular weight, M/G block ratios, alginate lyase enzyme concentrations, and metal ion binding affinities, allowing for predictable and controlled embolism induction without additional post-embolization procedures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If existing embolic agents (IMP/CS particles, Gelfoam, collagen) are used for temporary embolization, then embolization can be achieved, but the dissolution rate is unpredictable and degradation time is uncontrolled (ranging from days to months)
Solution Approach 1:
The patent applies parameter changes by systematically varying alginate molecular weight (100-1000 kD), M/G block ratios (20:80 to 80:20), and alginate lyase concentrations (0.1-10 U/mL) to precisely control particle degradation kinetics. This enables tailoring embolization duration from 1-7 days to 1-4 weeks while maintaining predictable dissolution rates, directly resolving the contradiction between duration control and reliability.
Solution Approach 2:
The invention creates a composite material system combining alginate polymer matrix with embedded alginate lyase enzyme and metal ions (Ca2+, Ba2+). This composite structure enables self-degradation through enzymatic hydrolysis, providing controlled and predictable dissolution rates that neither component could achieve alone, thus improving reliability while maintaining customizable duration.
2Ease of manufacture
If existing embolic agents are used, then embolization can be performed, but migration of agents causes non-specific occlusion requiring additional procedures
Solution Approach 1:
The alginate particles are engineered with embedded alginate lyase that enables self-degradation within the body without requiring external dissolution agents or additional procedures. The particles automatically dissolve after completing their embolization function, eliminating the harmful effect of non-specific occlusion while maintaining procedural simplicity.
Solution Approach 2:
The patent extracts and eliminates the problematic component (persistent embolic material requiring manual removal) by designing particles that naturally degrade and are absorbed by the body. The alginate lyase enzyme catalyzes the breakdown of alginate into absorbable oligosaccharides, removing the need for additional dissolution procedures.
3Ease of operation
If Gelfoam is used as embolic agent, then embolization can be achieved, but additional preparation steps (cutting into pledgets or slurrying) are required
Solution Approach 1:
The alginate particles are pre-formed with controlled size (50-500 μm), composition, and degradation properties during manufacturing. They are supplied ready-to-use in sterile suspension, eliminating the need for bedside preparation steps such as cutting Gelfoam into pledgets or preparing slurries, thus improving ease of operation while reducing procedural complexity.
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 self-degrading alginate particles provide a safe and effective means of temporary embolization with minimal risk of non-specific occlusions, as they degrade predictably, reducing the need for additional procedures and enhancing patient safety.
Implementation Method 1
the metal ions cross-link the alginate molecules to form an alginate matrix
Implementation Method 2
the self-degrading alginate particle comprises alginate lyase enzymes
Implementation Method 3
degradation of the alginate particle
Data Source
AI summary
The present disclosure provides compositions including self-degrading alginate particles comprising alginate, alginate lyase, and divalent metal ions. The present disclosure also provides methods of making compositions including self-degrading alginate particles comprising alginate, alginate lyase, and divalent metal ions. The present disclosure also provides methods of inducing an embolism in a subject in thereof, and syringes containing the compositions of the present disclosure for use in the methods thereof.