Surgery – Controlled release therapeutic device or system – Implanted dynamic device or system
Reexamination Certificate
1998-09-24
2004-02-10
Lo, Weilun (Department: 3761)
Surgery
Controlled release therapeutic device or system
Implanted dynamic device or system
C424S423000
Reexamination Certificate
active
06689121
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.
Existing systems for local drug delivery, including direct deposition of therapeutic agents 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, all require a functioning vascular system for delivery of the therapeutic agent to the affected tissue. These systems, therefore, are inapplicable in conditions characterized by myocardial ischemia or infarction. When ischemic injury is of sufficient severity and duration, groups of involved cells die and myocardial infarction results. Within the ischemic area, not all cells are equally injured. As ischemia persists, there is wave-like progression of cell death or coagulation necrosis. The prospect for recovery decreases with increasing duration or severity of the ischemic insult. It is difficult to quantitate the extent to which ischemic injury will result in cell necrosis.
Reperfusion can salvage injured tissue even after some cells have become necrotic. However, following reperfusion, cells that have been already injured are particularly vulnerable to further injury. This phenomenon, termed “reperfusion injury,” paradoxically results in cellular necrosis when circulation returns to a cell population that survived the initial ischemic insult. Many factors contribute to this situation. The endothelium of vessels in the reperfused region have been damaged, causing platelet adherence and leukocyte activation with inflammatory sequelae. Oxygen free radicals are released by damaged cells, causing further cell and organelle damage. The sodium-potassium pump, damaged with the initial ischemia, can lose its regulatory ability and allow free water accumulation during reperfusion, resulting in cell swelling and rupture. Unstable and leaky cell membranes can also lead to calcium accumulation within the cytoplasm with uptake of calcium into mitochondria and formation of insoluble calcium-phosphate crystals. As a consequence, there may be a population of cells killed by the initial ischemic insult, and a further population killed following reperfusion.
Both ischemia and infarction can adversely affect myocardial contractile function. The more extensive the injury, the more severe its impact on ventricular function. Following severe myocardial ischemia, there may be a reversible hypocontractile state called “hibernation,” a condition of impaired contractility amenable to recovery (the so-called “stunned” myocardium, and frank myocardial infarction, characterized by cell death. Once a population of myocytes becomes necrotic, the injured tissue cannot regenerate itself; mature myocytes lack the capacity for cellular replication. The contribution these necrotic myocytes made to contractile function is, thus irreversibly lost. Restoration of functioning myocardium after frank infarction requires both a restoration of tissue perfusion and a replenishing of viable cells that can assume the contractile role of the infarcted tissues.
In view of the variety of localized cardiovascular conditions affecting human health, 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. It would furthermore be advantageous to permit treatment of localized cardiovascular conditions resulting from myocardial ischemia and myocardial infarction through local delivery of therapeutic agents.
SUMMARY OF THE INVENTION
It is therefore, an object of the invention to provide methods of treatment of a coronary artery or cardiac indication t
C. R. Bard Inc.
Lo Weilun
LandOfFree
Systems and methods for treating ischemia 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 treating ischemia, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Systems and methods for treating ischemia will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3351186