Drug-delivery stent formulations for restenosis and vulnerable plaque

Abstract

Drug-delivery stents capable of providing release of two or more drugs such as everolimus and estradiol are provided. The stents can be used for treating a disease such as restenosis and vulnerable plaque.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] This invention relates to drug combinations, formulations, and methods of application for the treatment or prevention of vascular disorder such as restenosis and / or vulnerable plaque. More superficially, the invention relates to application of everolimus and estradiol such as by a stent. [0003] 2. Description of the Background [0004] Plaques have been associated with stenosis and restenosis. While treatments of plaque-induced stenosis and restenosis have advanced significantly over the last few decades, the morbidity and mortality associated with vascular plaques have remained significant. Recent work suggests that plaques may generally fall into one of two different general types: standard stenotic plaques and vulnerable plaques. Stenotic plaque, which is sometimes referred to as thrombosis-resistant plaque, can generally be treated effectively by the known intravascular lumen opening techniques. Although the steno...

AI Technical Summary

Benefits of technology

[0012] The release profiles of the drugs are tailored to meet various therapeutic needs. Therapeutic intervention of a drug may vary as a function of time because the mechanistic target of the drug may be a function of time. For example, anti-proliferative drugs may need to be released between 5 days to 30 days after implantation, and anti-inflammatory or antiplatelet drugs may need to be delivered acutely during the implantation procedure followed by a sustained release up to 2 months after implantation. Antimigratory drugs may need to be released within 1-4 weeks. The coating described herein, in one embodiment, is capable of providing a pulse or fast release of a first drug followed by a sustained release the first drug. The coating can further provide a fast release and / or followed by a sustained release of a second drug over a defined period.

[0013] A stent having a coating formulation defined herein can be used to treat or prevent a disorder such as atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, ureter obstruction, tumor obstruction, and combinations thereof.

Problems solved by technology

While treatments of plaque-induced stenosis and restenosis have advanced significantly over the last few decades, the morbidity and mortality associated with vascular plaques have remained significant.

Unfortunately, as plaque matures, narrowing of a blood vessel by a proliferation of smooth muscle cells, matrix synthesis, and lipid accumulation may result in formation of a plaque which is quite different than a standard stenotic plaque.

Such atherosclerotic plaque becomes thrombosis-prone, and can be highly dangerous.

Blood cells may collect around the plaque, eventually creating a blood clot that may block the artery completely.

The phenomenon of “vulnerable plaque” has created new challenges in recent years for the treatment of heart disease.

As such, conventional methods for detecting heart disease, such as an angiogram, may not detect vulnerable plaque growth into the arterial wall.

The fibrous cap contains mostly collagen, whose reduced concentration combined with macrophage derived enzyme degradations can cause the fibrous cap of these lesions to rupture under unpredictable circumstances.

It is thought that hemodynamic and cardiac forces, which yield circumferential stress, shear stress, and flexion stress, may cause disruption of a fibroatheroma type of vulnerable plaque.

While the known procedures for treating plaque have gained wide acceptance and shown good efficacy for treatment of standard stenotic plaques, they may be ineffective (and possibly dangerous) when thrombotic conditions are superimposed on atherosclerotic plaques.

Specifically, mechanical stresses caused by primary treatments like percutaneous transluminal coronary intervention (PTCI), such as stenting, may actually trigger release of fluids and / or solids from a vulnerable plaque into the blood stream, thereby potentially causing a coronary thrombotic occlusion.

There is evidence that fibrous cap can be ruptured during stent deployment.

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