Coating compositions for bioactive agents

Abstract

A coating composition and related method for use in applying a bioactive agent to a surface in a manner that will permit the bioactive agent to be released from the coating in vivo. The composition is particularly well suited for coating the surface of implantable medical device, such as a stent or catheter, in order to permit the device to release bioactive agent to the surrounding tissue over time. The composition includes a plurality of compatible polymers having different properties that can permit them to be combined together to provide an optimal combination of such properties as durability, biocompatibility, and release kinetics.

Description

RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 559,821, titled Coating Compositions for Bioactive Agents, filed Apr. 6, 2004, the contents of which are hereby incorporated by reference. This application is related to PCT Application Ser. No._______, filed Apr. 6, 2005, titled Coating Compositions for Bioactive Agents and identified by Attorney Docket No. 9896.166.7, as well as PCT Application Ser. No._______ filed Apr. 6, 2005, titled Coating Compositions for Bioactive Agents and identified by Attorney Docket No. 9896.166.8, the contents of both of which are hereby incorporated by reference.TECHNICAL FIELD [0002] In one aspect, the present invention relates to a method of treating implantable medical devices with coating compositions to provide for the controlled release of bioactive (e.g., pharmaceutical) agents from the surface of the devices under physiological conditions. In another aspect, the invention relates to the...

AI Technical Summary

Benefits of technology

[0011] With regard to its formulation, a coating composition of this invention may be provided in the form of a true solution by the use of one or more solvents. Such solvents, in turn, are not only capable of dissolving the polymers and bioactive agent in solution, as compared to dispersion or emulsion, but they are also sufficiently volatile to permit the composition to be effectively applied to a surface (e.g., as by spraying) and quickly removed (e.g., as by drying) to provide a stable and desirable coated composition. In turn, the coated composition is itself homogeneous, with the first and second polymers effectively serving as cosolvents for each other, and bioactive agent substantially equally sequestered within them both.

[0012] The ability to form a true solution using the claimed polymer combinations may be desirable when considering the inclusion of potentially significant amounts of bioactive agent with the polymer blend. In various embodiments of the present invention, the coating composition is not only in the form of a true solution, but one in which bioactive agent is present at saturated or supersaturated levels. Without intending to be bound by theory, it appears that it is by virtue of the ability to achieve such solutions, that release of the bioactive agent from the coated composition is best accomplished and facilitated. In turn, it appears that the release of bioactive agent from such a system is due, at least in part, to its inherent instability within the coated composition itself, coupled with its physical / chemical preference for surrounding tissues and fluids. In turn, those skilled in the art will appreciate the manner in which the various ingredients and amounts in a composition of this invention can be adjusted to provide desired release kinetics and for any particular bioactive agent, solvent and polymer combination.

[0013] With regard to its delivery, a composition of this invention may meet or exceed further criteria in its ability to be sterilized, stored, and delivered to a surface in a manner that preserves its desired characteristics, yet using conventional delivery means, such as spraying. Such delivery may involve spraying the composition onto a device surface in a manner that avoids or minimizes phase separation of the polymer components.

[0015] In turn, compositions of the present invention provide properties that are comparable or better than those obtained with previous polymer blend compositions. This, in turn, provides a variety of new and further opportunities, including with respect to both the type and concentration of bioactive agents that can be coated, as well as the variety of medical devices, and surfaces, themselves. In turn, the present invention also provides a combination that includes a medical device coated with a composition of this invention, as well as a method of preparing and using such a combination.

Problems solved by technology

Many individuals suffer from circulatory disease caused by a progressive blockage of the blood vessels, which often leads to hypertension, ischemic injury, stroke, or myocardial infarction.

A limitation associated with PTCA is the abrupt closure of the vessel which can occur soon after angioplasty.

. . ), after placement in the body, can give rise to numerous physiological complications.

Some of these complications include: increased risk of infection; initiation of a foreign body response resulting in inflammation and fibrous encapsulation; and initiation of a detrimental wound healing response resulting in hyperplasia and restenosis.

These problems have been particularly acute with the placement of stents in damaged arteries after angioplasty.

Although the potential benefit from using such bioactive agent-releasing medical devices is great, development of such medical devices has been slow.

Progress has been hampered by many challenges, including: 1) the requirement, in some instances, for long term (i.e., at least several weeks) release of bioactive agents; 2) the need for a biocompatible, non-inflammatory device surface; 3) the demand for significant durability (and particularly, resistance to delamination and cracking), particularly with devices that undergo flexion and / or expansion when being implanted or used in the body; 4) concerns regarding the ability of the device to be manufactured in an economically viable and reproducible manner; and 5) the requirement that the finished device can be sterilized using conventional methods.

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