Crystalline Cilostazol Stent Coating for Sustained Peripheral Drug Release

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Solution Overview

Problem

Existing drug-eluting stents for coronary arteries release drugs too quickly, leading to insufficient treatment duration for peripheral artery diseases, which require a longer therapeutic effect due to thinner and more delicate blood vessels.

Innovation Solution

A stent design with multiple layers of crystalline cilostazol and bioabsorbable polymers, specifically formulated to control drug release over an extended period, allowing not more than 5% elution by 24 hours and not more than 20% by 15 days, suitable for peripheral blood vessels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a drug-eluting stent uses limus drugs with strong cytotoxicity to suppress intimal thickening, then restenosis is effectively prevented, but vascular endothelial cell regeneration is suppressed leading to delayed in-stent thrombosis

Engineering Contradiction:

Improverestenosis preventionVSAvoiddelayed in-stent thrombosis

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the drug parameter from limus drugs to cilostazol, which has different pharmacological properties (non-cytotoxic platelet aggregation inhibitor). This parameter change allows achieving restenosis prevention through a different mechanism while avoiding the harmful effect of endothelial cell suppression and subsequent thrombosis

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent converts the previously harmful rapid elution effect into a beneficial sustained release effect by using a bioabsorbable polymer coating. The rapid elution that caused thrombosis is transformed into controlled sustained release that maintains therapeutic effect without peak concentration toxicity

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Speed

If a stent coating releases drug quickly to achieve immediate therapeutic effect, then initial drug concentration is sufficient, but treatment duration is insufficient for peripheral artery diseases

Engineering Contradiction:

Improvedrug release speedVSAvoidtreatment duration

Core Design Contradiction:

SpeedVSDuration of action of moving object

Solution Approach 1:

The patent creates a dynamic drug release system where the release rate changes over time. The bioabsorbable polymer coating provides initial controlled release and then gradually degrades, transitioning from slower initial release to sustained release over 6-12 months, adapting to the different phases of healing and restenosis prevention needs

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent changes the physical state parameter of the drug from amorphous to crystalline form. Crystalline cilostazol provides controlled solubility and sustained release characteristics, enabling the drug to maintain therapeutic levels over the extended 6-12 month period required for peripheral artery disease treatment

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If cilostazol is prepared with poor water solubility, then drug stability is improved, but preparation difficulty increases

Engineering Contradiction:

Improvedrug stabilityVSAvoidpreparation difficulty

Core Design Contradiction:

Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent creates a composite material system combining crystalline cilostazol with a bioabsorbable polymer coating. This composite structure allows the poorly water-soluble crystalline drug to be delivered effectively through the polymer matrix, which controls release and improves manufacturability despite the drug's solubility limitations

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The bioabsorbable polymer coating creates a porous matrix structure that accommodates the crystalline cilostazol. This porous structure allows controlled drug release while simplifying the preparation process, as the polymer matrix can be applied as a coating that incorporates the crystalline drug particles

Inventive Principle:

Principle #31Porous materials

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 stent provides sustained drug release for 6 to 12 months, effectively treating peripheral artery diseases with minimal invasiveness and reducing restenosis, while maintaining vascular health.

Implementation Method 1

a deposition layer containing a plurality of layers deposited on the stent skeleton; each layer of the deposition layer comprising crystalline cilostazol

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

elution of not more than 5% by mass of the crystalline cilostazol occurs by 24 hours

Methodology Applied

Scientific EffectDissolution: Solvation

Data Source

PatentUS12485026B2Drug-eluting stent including crystalline cilostazol

Publication Date: 2025.12.02 OTSUKA MEDICAL DEVICES

AI summary

Provided is a stent comprising: a stent skeleton; and a deposition layer containing a plurality of layers deposited on the stent skeleton; each layer of the deposition layer comprising crystalline cilostazol, at least one of the plurality of layers comprising a bioabsorbable polymer.