mTOR Inhibitor Coated Stent Layered Release
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Solution Overview
Problem
Current implantable medical devices, such as stents, face challenges in achieving controlled drug release of mTOR inhibitors to prevent restenosis, as non-degradable polymers can cause delayed endothelization, late stent thrombosis, and local hypersensitivity, while biodegradable polymers often result in high initial drug bursts or inadequate release due to uncontrolled drug delivery.
Innovation Solution
A coated implantable medical device with a three-layer structure: a base and middle layer comprising mTOR inhibitors and biodegradable polymers, and a top layer of hydrophilic polymer and antioxidant, ensuring a total mTOR inhibitor concentration of 0.7 to 3.00 μg/mm², which allows for a controlled and prolonged release of the drug through diffusion, preventing adverse effects and maintaining therapeutic levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If non-degradable polymers are used for drug delivery, then the device structure is stable and durable, but delayed endothelization, late stent thrombosis, and local hypersensitivity occur
Solution Approach 1:
The patent changes the chemical composition parameter of the polymer from non-degradable to biodegradable, fundamentally altering the material's lifecycle and interaction with biological systems. This parameter change eliminates the harmful effects associated with permanent polymers while maintaining structural integrity during the required delivery period.
Solution Approach 2:
The invention uses composite material formulation by combining biodegradable polymer with specific pharmaceutical ingredients (mTOR inhibitors like everolimus or sirolimus) and potential additives such as antioxidants or anti-inflammatory agents. This composite approach allows optimization of both structural stability and biocompatibility.
2Object-affected harmful factors
If biodegradable polymers are used for drug delivery, then biocompatibility improves, but high initial drug burst or inadequate release occurs
Solution Approach 1:
The patent applies local quality by creating a multi-layer coating structure where different regions have distinct compositions and drug loading characteristics. The abluminal and luminal surfaces may have different polymer ratios, drug concentrations, or layer thicknesses, allowing independent optimization of initial burst control and sustained release profiles for each surface.
Solution Approach 2:
The invention systematically varies multiple parameters including polymer molecular weight, crystallinity, drug-polymer ratio, layer thickness, and crosslinking degree to fine-tune the release kinetics. These parameter adjustments enable precise control over drug release rates while maintaining biocompatibility.
3Quantity of substance
If high drug concentration is delivered initially, then adequate anti-proliferative effect is achieved, but local toxic events occur
Solution Approach 1:
The patent implements periodic action through time-dependent drug release profiling, where the drug is delivered in a controlled sequence: a moderate initial release followed by sustained prolonged release over months. This temporal distribution prevents toxic peak concentrations while ensuring adequate therapeutic exposure over the critical healing period.
Solution Approach 2:
The biodegradable polymer acts as an intermediary carrier that mediates between the drug and biological tissue. It controls the interface interaction by regulating drug release kinetics, preventing direct toxic exposure while maintaining therapeutic efficacy through controlled delivery to the target tissue.
4Object-affected harmful factors
If low drug concentration is delivered, then local toxic events are minimized, but inadequate anti-proliferative effect occurs
Solution Approach 1:
The patent ensures continuity of useful action by designing a sustained release system that maintains therapeutic drug levels continuously over an extended period (3-12 months). This continuous low-to-moderate dose delivery prevents toxic peaks while avoiding sub-therapeutic valleys, ensuring reliable anti-proliferative effect throughout the critical restenosis prevention period.
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 device achieves a controlled and prolonged release of mTOR inhibitors, reducing the risk of restenosis by maintaining therapeutic levels and minimizing adverse effects, with an average 20% release at day 1 and stable release over time, effectively targeting smooth muscle cell proliferation.
Implementation Method 1
controlled drug release is required to target the biochemical mechanisms during specific time periods
Implementation Method 2
a top layer selected from the group consisting of hydrophilic polymer, and combination of hydrophilic polymer and antioxidant
Data Source
AI summary
The present disclosure relates to a coated implantable medical device, comprising: a base layer comprising mTOR inhibitor, and at least one biodegradable polymer; a middle layer comprising mTOR inhibitor, and at least one biodegradable polymer; and a top layer selected from the group consisting of hydrophilic polymer, and combination of hydrophilic polymer and antioxidant, wherein the total mTOR inhibitor concentration over the medical device is in the range of 0.7 to 3.00 μg/mm2. The present disclosure further relates to a method of preparing a coated implantable medical device.