Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Reexamination Certificate
1997-12-18
2001-06-26
Azpuru, Carlos A. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
Reexamination Certificate
active
06251418
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the local delivery of therapeutic agents, and more particularly, to systems and methods that deliver depots of therapeutic agents into a body of tissue to allow for the treatment of a variety of conditions, including coronary conditions and cardiovascular indications.
BACKGROUND OF THE INVENTION
Disease, injury and surgery can result in localized tissue damage and morbidity. For example, the principal treatment for occlusive vascular diseases is angioplasty, a procedure in which a balloon is inserted into the vessel and then inflated to dilate the area of narrowing. During inflation, the balloon can damage the vessel wall. It appears that as a result of this damage, in 30 to 50% of cases, the initial increase in lumen dimensions is followed by a localized re-narrowing (restenosis) of the vessel over a time of three to six months. Thus, restenosis can result in the dangerous and localized renarrowing of a patient's vessel at the site of the recent angioplasty. Like many other localized diseases, restenosis is complex and at present there is no clinically effective treatment for this disease. Gibbons et al.,
Molecular Therapies for Vascular Diseases,
Science vol. 272, pages 617-780 (May 1996).
Restenosis, like many other localized injuries and diseases, has responded poorly to pharmacological therapies and agents. Numerous pharmacological agents have been clinically tested, and none have demonstrated an unequivocal reduction in the incidence of restenosis. However, the failure of these pharmacological therapies may arise from the systemic intolerance of the doses required to achieve local beneficial effects or in the difficulty of providing controlled administration of proper dosages over time. Accordingly, one possible reason for the failure of these therapies is that submaximal doses of pharmacological agents are being administered to avoid the serious side-effects that might result from systemic administration of the proper dosage.
To address this problem, various researchers have proposed methods for site-specific delivery of pharmacologic and molecular therapies. These methods include the direct deposition of therapeutic agents into the arterial wall through an intravascular delivery system, systemic administration of therapeutic agents that have a specific affinity for the injured or diseased tissue, and systemic administration of inactive agents followed by local activation.
At present, systems exist that attempt to achieve localized delivery of therapeutic agents. These systems include dual balloon delivery systems that have proximal and distal balloons that are simultaneously inflated to isolate a treatment space within an arterial lumen. A catheter extends between the two balloons and includes a port that can admit within the treatment space between the balloons an aqueous medium, typically one containing a therapeutic agent. Pressure can be applied to the medium to create conditions conducive to intramural infusion. Other balloon-based localized delivery systems include porous balloon systems, hydrogel-coated balloons and porous balloons that have an interior metallic stent. Other systems include locally placed drug-loaded coated metallic stents and drug-filled polymer stents. Wilensky et al.,
Methods and Devices for Local Drug Delivery in Coronary and Peripheral Arteries,
Trend Cardiovasc Med, vol. 3 (1993).
Although these systems can provide working devices for local drug delivery, the efficacy of these devices turns on, and is limited by, a number of factors including the rate of fluid flux through the vascular wall, the residence time of the deposited agent and the local conditions and vasculature of the deposition site. Essentially, the success of these systems is limited by the amount of time that a delivered drug will stay resident locally before being carried downstream by circulating blood. Further, to the extent that these systems allow the therapeutic agent to be carried away, these systems run the risk of applying a therapeutic agent to areas of the patient's vasculature where such agents may not be beneficial. Additionally, these existing systems are limited by the amount of drug that can be delivered to the diseased site. Moreover, drug filled polymer stents have structural problems that argue against their use.
It would be advantageous to develop other methods of treatment for patients having localized cardiovascular conditions and in particular to develop methods of treatment that reduce adverse side effects and have heightened efficacy.
SUMMARY OF THE INVENTION
It is therefore, an object of the invention to provide methods of treatment of a coronary artery or cardiac indication that provide a longer duration of drug pendency at the site of a localized disease.
It is a further object of the invention to provide systems and methods that reduce or eliminate the downstream flow of a locally delivered agent.
Other objects of the invention will, in part, be obvious, and, in part, be shown from the following description of the systems and methods shown herein.
To these ends, the invention provides systems and methods for implanting a depot into a tissue wall to thereby deliver a therapeutic agent selected for the condition being treated. In one embodiment, the invention provides systems and methods for delivering a therapeutic agent into the myocardial tissue wall for treating various vascular conditions including restenosis, ischemic tissue, and myocardial infarction. Other applications of the systems and methods described herein include the delivery of angiogenesis compounds that can be implanted into ischemic tissue; and/or antiarrhythmic drugs that can be implanted at the sites of conduction abnormalities. Accordingly, the agent being locally delivered can depend on the application at hand, and the term agent, or therapeutic agent, as employed herein will be understood to encompass any agent capable of being locally delivered including, but not limited to, pharmaceutical compositions or formulations, viral or non-viral vectors (e.g., adenovirus vectors, retroviral vectors and the like), implantable (genetically engineered) cells, plasmid-liposome complexes or other DNA delivery complexes, oligonucleotides or any other suitable composition compatible with the subject being treated.
In one embodiment the invention is understood as apparatus for delivering therapeutic agents, comprising an elongate flexible body having a proximal end and a distal end, a delivery chamber coupled to the distal end of the body and having a space for carrying the therapeutic agent, and a port for releasing the therapeutic agent therefrom. The apparatus further includes an actuator coupled to the distal delivery chamber and being capable of driving therapeutic agent through the port.
The terms proximal and distal as used herein will be understood to describe opposite ends of a device or element, and generally will be employed so that proximal is understood as “away from the heart” and distal is understood as “towards the heart” or to mean “toward the physician” and “away from the physician” respectively.
In one embodiment, the apparatus further includes a control mechanism that couples to the actuator and to the proximal end of the body for providing control of the actuator. In this way a user can operate the control mechanism for selectable delivery of the agent. Optionally, the apparatus can also include a “steering” mechanism for bending the distal end of the body to thereby allow the delivery chamber to be selectively aimed for directed within the chambers of the heart. The distal end of the flexible body can be dimensionally adapted to allow for transluminal delivery and for entry into the interior of a patient's heart. This allows the distal end of the apparatus, which carries the delivery chamber, to travel through the patient's vasculature, enter the patient's heart, and butt against or penetrate through the endocardial tissue and penetrate into the myocardium. To this end, the distal end of th
Ahern John E.
Crittenden James F.
Azpuru Carlos A.
C.R. Bard Inc.
LandOfFree
Systems and methods for local delivery of an agent does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Systems and methods for local delivery of an agent, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Systems and methods for local delivery of an agent will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2531516