Drug Coating Layer Crystalline Morphology for Stenosis Inhibition
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Solution Overview
Problem
Current drug eluting balloons with crystalline paclitaxel coatings face challenges in achieving a balance between high intravascular stenosis inhibitory effect and low toxicity, with existing technologies not adequately addressing the morphological form of drug crystals and their impact on tissue transferability and toxicity.
Innovation Solution
A drug coating layer with specific crystalline morphological forms, including elongate bodies with nearly linear long axes forming angles between 45° to 135°, hollow structures, and a surface covered with an amorphous film, is developed, featuring crystals of water-insoluble drugs like paclitaxel, rapamycin, or docetaxel, arranged with regularity and excipient particles, to enhance drug transfer and reduce toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If crystalline form paclitaxel is used in drug eluting balloon, then tissue transferability of drugs is improved, but toxicity to target tissue increases
Solution Approach 1:
The patent applies local quality by creating different crystalline morphological forms in different regions of the drug coating layer. Specifically, it produces elongate body crystals with aspect ratios of 2:1 to 10:1 that have improved tissue transferability while controlling their distribution to minimize toxicity. The crystal morphology is locally optimized rather than using uniform crystal forms throughout the coating.
Solution Approach 2:
The patent changes physical parameters of the crystal structure, specifically controlling the aspect ratio of elongate bodies to be 2:1 to 10:1 and the crystal size to be 1 μm to 100 μm. These parameter changes in crystal morphology improve tissue transferability while the controlled distribution and morphology reduce toxicity, resolving the contradiction between efficacy and safety.
2Reliability
If crystalline form paclitaxel is used in drug eluting balloon, then intravascular stenosis inhibitory effect is improved, but toxicity to target tissue increases
Solution Approach 1:
The patent creates locally optimized crystal structures with elongate body morphology (aspect ratio 2:1 to 10:1) that provide high intravascular stenosis inhibitory effect at the treatment site while controlling crystal distribution to minimize systemic toxicity. The local crystal morphology is specifically designed to maximize therapeutic effect where needed.
Solution Approach 2:
The patent changes crystal morphology parameters to elongate bodies with aspect ratios of 2:1 to 10:1 and sizes of 1 μm to 100 μm. These parameter changes enhance the intravascular stenosis inhibitory effect through improved drug release characteristics while the controlled crystal properties reduce toxicity, achieving both high efficacy and safety.
3Ease of manufacture
If amorphous drug form is used in coating layer, then manufacturing is simpler, but tissue transferability and releasing property are reduced
Solution Approach 1:
The patent utilizes phase transition from amorphous to crystalline form during the coating process. By controlling the drying and curing conditions, the drug transitions from an amorphous state in the coating solution to a crystalline elongate body structure in the final coating layer. This phase transition achieves both manufacturability and improved tissue transferability.
Solution Approach 2:
The patent changes the physical state of the drug from amorphous in the coating solution to crystalline elongate bodies in the dried coating layer. By controlling crystallization parameters such as solvent evaporation rate and curing temperature, the process achieves both ease of manufacture and high tissue transferability through the resulting crystal morphology.
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 drug coating layer achieves a high intravascular stenosis inhibitory effect while minimizing toxicity by optimizing drug solubility and retentivity in tissues, ensuring effective drug action and reduced side effects.
Implementation Method 1
a morphological form including a plurality of elongate bodies with long axes, each crystal of a water-insoluble drug independently having on a substrate surface
Implementation Method 2
the surface of the crystal of the water-insoluble drug is further covered with an amorphous film
Data Source
Figure 1A~1C
Figure 1D~3A
Figure 3B~5
AI summary
[Problem] The present invention is to provide a drug coating layer which has low toxicity and a high intravascular stenosis inhibitory effect, when delivering medical device coated with a drug into the body and medical device using the same. The drug coating layer is a drug coating layer having a morphological form including a plurality of elongate bodies having long axes that each crystal of a water-insoluble drug independently has on a substrate surface, in which the long axes of the elongate bodies are nearly linear in shape, and the long axes of the elongate bodies form an angle in a predetermined range with respect to a substrate plane with which the long axis of the elongate body intersects.