Liquid Vascular Embolic Agent for Stable Microvessel Embolization
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Solution Overview
Problem
Existing vascular embolic agents face issues such as vessel rupture, recanalization, agglomeration, rapid polymerization, chronic inflammation, poor migration, and separation of contrast agents, leading to incomplete or ectopic embolization, with current materials lacking stable mechanical properties and effective drug loading.
Innovation Solution
A vascular embolic agent prepared by dissolving a 1,2-dithiolane compound, polyphenol compound, and alkaloid in an organic solvent, reacting at 70°C for 5-12 hours, and diluting with another solvent to form a cross-linked gel that adheres to blood vessels, using a contrast agent for precise positioning.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If spring coils are used as embolic material, then embolization effect is achieved, but vessel rupture may occur and over-tortuous blood vessels cannot be reached
Solution Approach 1:
The patent changes the physical state parameter of the embolic agent from solid (spring coils) to liquid, which can then be delivered through catheters to reach target vessels without causing mechanical vessel rupture. The liquid agent polymerizes in situ to achieve embolization, resolving the contradiction between effective occlusion and vessel damage.
Solution Approach 2:
The patent replaces the mechanical embolic system (spring coils that physically block vessels) with a chemical system (liquid embolic agent that polymerizes in situ). This substitution allows the agent to flow through complex vasculature without mechanical trauma and then solidify to achieve embolization, eliminating the vessel rupture problem while maintaining therapeutic effect.
2Reliability
If nBCA is used as liquid embolic material, then rapid polymerization creates embolus, but poor migration and adhesion to catheters occurs
Solution Approach 1:
The patent uses a composite liquid embolic system comprising a polymer precursor, contrast agent, and solvent. The contrast agent enhances visibility during delivery, the solvent controls viscosity for easy catheter injection, and the polymer precursor provides controlled polymerization. This composite formulation resolves the contradiction between rapid embolus formation and ease of delivery by balancing reactivity with deliverability.
Solution Approach 2:
The patent introduces a solvent as an intermediary that temporarily maintains the embolic agent in a low-viscosity liquid state for easy catheter injection and migration. Once injected into the target vessel, the solvent evaporates or is diluted by blood, triggering polymerization. This intermediary approach separates the delivery phase from the embolization phase, resolving the contradiction between migration ease and embolus formation.
3Reliability
If Onyx is used as liquid embolic material, then embolization is achieved, but non-degradability causes local chronic inflammation and rejection
Solution Approach 1:
The patent changes the chemical composition parameter of the embolic agent from non-degradable (Onyx) to biodegradable components. The liquid embolic agent uses polymer precursors that can be metabolized by the body after achieving embolization, transforming the material from permanently foreign to temporarily present, thus resolving the contradiction between stable embolization and reduced inflammatory response.
4Ease of operation
If iodide oil is used as liquid embolic material, then fluidity is achieved, but easy vessel recanalization and poor embolization occur
Solution Approach 1:
The patent introduces dynamic properties to the embolic agent: it starts as a liquid for easy injection (mimicking iodide oil's fluidity advantage) but then undergoes polymerization to become a solid gel that provides stable embolization (resolving iodide oil's recanalization problem). This dynamic state transition allows the agent to exhibit both high fluidity during delivery and high stability during embolization.
5Quantity of substance
If embolic agents cannot be tightly cross-linked, then drug loading is achieved, but contrast agent separation occurs leading to incomplete or ectopic embolization
Solution Approach 1:
The patent merges the drug loading function with the cross-linking network formation. The liquid embolic agent incorporates drugs within its polymer matrix, and as the polymer cross-links and solidifies, it entraps the drugs in place. This merging of drug loading with network formation prevents contrast agent and drug separation, resolving the contradiction between maintaining drug availability and achieving precise embolization placement.
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 agent achieves stable mechanical properties, excellent biocompatibility, easy delivery to microvessels, and precise positioning without adhesion, enabling effective embolization and sustained drug release.
Implementation Method 1
A 1,2-dithiolane compound may be grafted onto the phenyl ring of a polyphenol compound via Michael addition reaction to form C—S bond between these two compounds
Implementation Method 2
The carboxyl group and the like of a 1,2-dithiolane compound may form a hydrogen bond with the phenolic hydroxyl group, carboxyl group or amino group of a polyphenol compound
Implementation Method 3
the alkaloid can neutralize the excess hydrogen ions in the system to reduce the cytotoxicity of the resulting product and avoid irritation of the blood vessel wall by the same, and also increase the cross-linking density of the resulting gel through the hydrogen bonding
Implementation Method 4
After being injected into physiological fluids (such as blood) as well as aqueous solutions, the vascular embolic agent can rapidly form a gel
Data Source
AI summary
Provided are a vascular embolic agent, a method for preparing same and use thereof. The method for preparing the vascular embolic agent comprises the following steps: (1) dissolving a 1,2-dithiolane compound, a polyphenol compound and an alkaloid in an organic solvent A to obtain a mixed solution A; (2) sealing the mixed solution A, and reacting same in an environment of 70° C. or above for 5-12 hours to obtain a mixed solution B; and (3) cooling the mixed solution B to room temperature, and adding an organic solvent B into the cooled mixed solution B for dilution to obtain the vascular embolic agent. The vascular embolic agent prepared by means of the method has outstanding biocompatibility, stable mechanical performance, excellent intravascular properties, is easily delivered to microvessels and complex-shaped target blood vessels, does not adhere to blood vessels, and can be developed without imaging artifacts.