US20060135943A1 - Method and apparatus for treating vulnerable plaque - Google Patents
Method and apparatus for treating vulnerable plaque Download PDFInfo
- Publication number
- US20060135943A1 US20060135943A1 US11/283,032 US28303205A US2006135943A1 US 20060135943 A1 US20060135943 A1 US 20060135943A1 US 28303205 A US28303205 A US 28303205A US 2006135943 A1 US2006135943 A1 US 2006135943A1
- Authority
- US
- United States
- Prior art keywords
- vulnerable plaque
- biologically active
- active agent
- needle
- plaque
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
- A61M25/0082—Catheter tip comprising a tool
- A61M25/0084—Catheter tip comprising a tool being one or more injection needles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M25/1006—Balloons formed between concentric tubes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/22—Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
- A61B2017/22081—Treatment of vulnerable plaque
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
- A61M25/0082—Catheter tip comprising a tool
- A61M2025/0096—Catheter tip comprising a tool being laterally outward extensions or tools, e.g. hooks or fibres
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
- A61M25/0023—Catheters; Hollow probes characterised by the form of the tubing by the form of the lumen, e.g. cross-section, variable diameter
- A61M25/0026—Multi-lumen catheters with stationary elements
Abstract
An apparatus and method to treat vulnerable plaque. In one embodiment, the apparatus has an elongated catheter body adapted for insertion in a body lumen, with a drug delivery device attached near a distal portion of the elongated body. The drug delivery device is configured to deliver a biologically active agent to stabilize a vulnerable plaque.
Description
- This application is a divisional application of co-pending U.S. patent application Ser. No. 10/262,151, filed Sep. 30, 2002.
- The invention, in one embodiment, relates generally to the treatment of coronary disease, and more particularly, in one embodiment, to the stabilization of vulnerable plaque.
- Coronary heart disease is generally thought to be caused by the narrowing of coronary arteries by atherosclerosis, the buildup of fatty deposits in the lining of the arteries. The process that may lead to atherosclerosis begins with the accumulation of excess fats and cholesterol in the blood. These substances infiltrate the lining of arteries, gradually increasing in size to form deposits commonly referred to as plaque or atherosclerotic occlusions. Plaques narrow the arterial lumen and impede blood flow. 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. Unlike occlusive plaques that impede blood flow, vulnerable plaque develops within the arterial walls, but it often does so without the characteristic substantial narrowing of the arterial lumen which produces symptoms. As such, conventional methods for detecting heart disease, such as an angiogram, may not detect vulnerable plaque growth into the arterial wall. After death, an autopsy can reveal the plaque congested in arterial wall that could not have been seen otherwise with currently available medical technology.
- The intrinsic histological features that may characterize a vulnerable plaque include increased lipid content, increased macrophage, foam cell and T lymphocyte content, and reduced collagen and smooth muscle cell (SMC) content. This fibroatheroma type of vulnerable plaque is often referred to as “soft,” having a large lipid pool of lipoproteins surrounded by a fibrous cap. 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. When ruptured, the lipid core contents, thought to include tissue factor, contact the arterial bloodstream, causing a blood clot to form that can completely block the artery resulting in an acute coronary syndrome (ACS) event. This type of atherosclerosis is coined “vulnerable” because of unpredictable tendency of the plaque to rupture. 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. These forces may rise as the result of simple movements, such as getting out of bed in the morning, in addition to in vivo forces related to blood flow and the beating of the heart. It is thought that plaque vulnerability in fibroatheroma types is determined primarily by factors which include: (1) size and consistency of the lipid core; (2) thickness of the fibrous cap covering the lipid core; and (3) inflammation and repair within the fibrous cap.
-
FIG. 1A illustrates a partial cross-section of an artery having a narrowed arterial lumen caused by the presence of occlusive atherosclerosis. Plaque accumulates to impede and reduce blood flow through the arterial lumen and thus often causes symptoms (e.g., angina pectoris). The arrows indicate the direction of blood flow through the arterial lumen.FIG. 1B illustrates an occlusive atherosclerosis within an arterial lumen resulting in significant reduction in lumen patency. This type of atherosclerosis can easily be detected through current diagnostic methods such as an angiogram.FIG. 1B also illustrates, downstream from the occlusive atherosclerosis, a fibroatheroma type of vulnerable plaque. The vulnerable plaque, with a lipid core, develops mostly within the arterial wall with minimal occlusive effects such that it is not easily detected by current diagnostic methods. This is partially due to a phenomenon known as “positive remodeling,” which allows the vessel to respond to the presence of disease. The fibroatheroma vulnerable plaque has grown into the positively remodeled arterial wall so that vessel occlusion has not been manifested. A fibrous cap surrounds the vulnerable plaque. -
FIGS. 2A-2C illustrate a cross-sectional view of the accumulation of vulnerable plaque in the arterial wall.FIG. 2A illustrates an arterial wall that is not affected by atherosclerosis. The normal arterial wall consists of an intima layer, a media layer, and an adventitia layer. The intima is in direct contact with the blood flow within the arterial lumen. The intima consists mainly of a monolayer of endothelial cells. The media consists mostly of smooth muscle cells and extracellular matrix proteins. The outermost layer of the arterial wall, the adventitia, is primarily collagenous and contains nerves, blood vessels, and lymph vessels.FIG. 2B illustrates the large presence of a fibroatheroma type vulnerable plaque surrounded by a fibrous cap within the arterial wall. The vulnerable plaque consists mainly of a large lipid core. The fibrous cap layer shields the lumen of the artery from the thrombogenic components in the core.FIG. 2C illustrates an occlusive thrombosis event resulting from the rupturing of the fibrous cap. Thrombogenic components in the vulnerable plaque contact luminal blood and cause the thrombotic event. - Autopsy studies and other evidence strongly suggest that the presence of a current acute coronary syndrome (ACS) event and/or existing thrombus at certain plaque sites may correlate to predicting a future ACS event in a given patient. The latter indicates the likelihood of a prior thrombotic event (e.g., fibroatheroma rupture) after which the plaque was able to heal itself, or complete occlusion of the vessel was somehow prevented. Autopsy studies also indicate that it is reasonable to expect that at least one vulnerable plaque could exist in the majority of catheterization laboratory patients being treated for arterial blockage from visible, occlusive atherosclerosis. Many of the patients at highest risk, therefore, for future ACS events may already be receiving interventional treatment, even though current methods to diagnose occlusive plaques (i.e., non-vulnerable type plaque) are not effective for enabling therapy for vulnerable plaque. Furthermore, treating both the occlusive plaques and the vulnerable plaque in one procedure might be beneficial and desirable compared to separate treatments. This would provide a greater convenience to the patient and for the physician.
- An apparatus and method to treat vulnerable plaque are described. In one embodiment, the apparatus has a an elongated catheter body adapted for insertion in a body lumen, with a drug delivery device attached near a distal portion of the elongated body. The drug delivery device is configured to deliver a biologically active agent to stabilize a vulnerable plaque.
- The present invention is illustrated by way of example, and not limitation, in the figures of the accompanying drawings in which:
-
FIG. 1A illustrates a partial cross-section of an arterial lumen having occlusive plaque. -
FIG. 1B illustrates a partial cross-section of an arterial lumen having occlusive plaque and vulnerable plaque. -
FIGS. 2A-2C illustrate the vessel morphology and the rupturing of a vulnerable plaque. -
FIGS. 3A-3B illustrate the stabilization a vulnerable plaque by reducing the size of the lipid core and strengthening and increasing the thickness of the fibrous cap. -
FIG. 4 illustrates one embodiment of using a drug delivery stent to treat a vulnerable plaque downstream from an occlusive plaque. -
FIGS. 5A-5C illustrate an alternative embodiment of using a drug delivery stent to treat a vulnerable plaque downstream from an occlusive plaque. -
FIG. 6 illustrates one embodiment of microparticles released towards a vulnerable plaque. -
FIG. 7 illustrates one embodiment of a stent graft used to treat a vulnerable plaque. -
FIGS. 8A-8B illustrate cross-sectional views of a stent graft. -
FIGS. 9A-9D illustrate various embodiments of using a needle catheter to treat a vulnerable plaque. -
FIGS. 10A-10B illustrate one embodiment of a needle catheter. -
FIGS. 11A-11D illustrate various methods for treating vulnerable plaque. -
FIG. 12 illustrates one embodiment of inducing therapeutic angiogenesis growth near a vulnerable plaque. -
FIGS. 13A-13B illustrate cross-sectional views of one embodiment of a drug eluting stent that can be used to strengthen and to increase the thickness of the fibrous cap of the vulnerable plaque in a controlled manner. - In the following description, numerous specific details are set forth such as examples of specific, components, processes, etc. in order to provide a thorough understanding of various embodiment of the present invention. It will be apparent, however, to one skilled in the art that these specific details need not be employed to practice various embodiments of the present invention. In other instances, well known components or methods have not been described in detail in order to avoid unnecessarily obscuring various embodiments of the present invention. The term “coupled” as used herein means connected directly to or indirectly connected through one or more intervening components, structures or elements. The terms “drugs,” “bioactive agents,” and “therapeutic agents” are used interchangeably to refer to agents (e.g., chemical substances) to treat, in one embodiment, coronary artery and related diseases including for example, atherosclerotic occlusions and vulnerable plaque.
- Apparatuses and their methods of use to treat vulnerable plaque are described. In one embodiment, the vulnerable plaque or the region of the artery containing the vulnerable plaque may be treated alone or in combination with treating occlusive atherosclerosis. The benefit is that any vulnerable, but not yet occlusive plaques would be treated without having to place a therapeutic implant (e.g., a stent) at the vulnerable plaque region. The only implant placed would be that already being used to scaffold and treat the existing occlusive plaque. In the following description, the stabilization of vulnerable plaque is described with respect to treatment within the artery. The coronary artery is just one region in the body where vulnerable plaque may form. As such, it can be appreciated that the stabilization of vulnerable plaque may be achieved in any vessel of the body where vulnerable plaque may exist.
-
FIGS. 3A-3B illustrate a cross-sectional view of the stabilization of vulnerable plaque.FIG. 3A shows a largevulnerable plaque 310 havinglipid core 315 separated fromarterial lumen 330 by thinfibrous cap 320. Thin fibrous caps and reduced collagen content or degraded collagen in the fibrous caps increase a plaque's vulnerability to rupture. As illustrated inFIG. 3B ,vulnerable plaque 310 has been stabilized by thickening and/or strengtheningfibrous cap 320 that separateslipid core 315 fromarterial lumen 330. This reduces the likelihood offibrous cap 320 rupturing. Additionally,lipid core 315 redistribution has occurred in combination with strengtheningfibrous cap 320.Vulnerable plaque 310 may also be treated by inducing collateral artery or vessel growth near the vulnerable plaque region such that, in the event of fibrous cap rupture or occlusive thrombosis, an alternative blood path exists to bypass the ruptured region (not shown). - Drug Eluting Stents
- In one embodiment, a drug eluting stent may be implanted at the region of vessel occlusion that may be upstream from a vulnerable plaque region. As discussed above, autopsy studies have shown that vulnerable plaque regions commonly exist in the vicinity of occlusive plaques. A medical device, such as a drug eluting stent, may be used to treat the occlusive atherosclerosis (i.e., non-vulnerable plaque) while releasing a drug or biologically active agent to treat a vulnerable plaque region distal or downstream to the occlusive plaque. The drug may be released slowly over time, and may include for example, anti-inflammatory or anti-oxidizing agents. Biologically active agents may also be released include cells, proteins, peptides, and related entities.
- The eluting stent may have the vulnerable plaque treating drug or agent dispersed on the surface of the stent, or co-dissolved in a matrix solution to be dispersed on the stent. Other methods to coat the stent with a vulnerable plaque treating drug include dip coating, spin coating, spray coating, or other coating methods commonly practiced in the art.
- In one embodiment, therapeutic or biologically active agents may be released to induce therapeutic angiogenesis, which refers to the processes of causing or inducing angiogenesis and arteriogenesis, either downstream, or away from the vulnerable plaque. Arteriogenesis is the enlargement of pre-existing collateral vessels. Collateral vessels allow blood to flow from a well-perfused region of the vessel into an ischemic region (from above an occlusion to downstream from the occlusion). Angiogenesis is the promotion or causation of the formation of new blood vessels downstream from the ischemic region. Having more blood vessels (e.g., capillaries) below the occlusion may provide for less pressure drop to perfuse areas with severe narrowing caused by a thrombus. In the event that an occlusive thrombus occurs in a vulnerable plaque, the myocardium perfused by the affected artery is salvaged. Representative therapeutic or biologically active agents include, but are not limited to, proteins such as vascular endothelial growth factor (VEGF) in any of its multiple isoforms, fibroblast growth factors, monocyte chemoatractant protein 1 (MCP-1), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta) in any of its multiple isoforms, DEL-1, insulin like growth factors (IGF), placental growth factor (PLGF), hepatocyte growth factor (HGF), prostaglandin E1 (PG-E1), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TBF-alpha), granulocyte stimulating growth factor (G-CSF), granulocyte macrophage colony-stimulating growth factor (GM-CSF), angiogenin, follistatin, and proliferin, genes encoding these proteins, cells transfected with these genes, pro-angiogenic peptides such as PR39 and PR11, and pro-angiogenic small molecules such as nicotine.
- In another embodiment, therapeutic or biologically active agents to treat the vulnerable plaque may be delivered through the bloodstream or vessel wall. These therapeutic or biologically active agents include, but are not limited to, lipid lowering agents, antioxidants, extracellular matrix synthesis promoters, inhibitors of plaque inflammation and extracellular degradation, estradiol drug classes and its derivatives.
- Prospective studies of high-risk patients in whom complex plaques were found have indicated that many of the ACS events can happen within six months to one year after a patient has an occlusive atherosclerosis lesion treated. In other words, there is a clinical reason to believe that it would be efficacious to try and actively treat lesions in those patients for a three to six-month period of time after treatment of occlusive atherosclerosis to prevent a recurrent ACS event. Examples of devices to treat vulnerable plaque regions include drug eluting stents, and drug loaded bioerodable and bioadhesive microparticles.
- In one embodiment, the polymer may be coated on a stent using dip coating, spin coating, spray coating or other coating methods known in the art. The drug can alternatively be encapsulated in microparticles or nanoparticles and dispersed in a stent coating. A diffusion limiting top-coat may optionally be applied to the above coatings. The active agents may optionally be loaded on a stent together either by adding them together to the solution of the matrix polymer before coating, or by coating different layers, each containing a different agent or combination of agents. The drug eluting stent can alternatively have an active agent or a combination of agents dispersed in a bioerodable stent forming polymer.
- Vulnerable plaque regions may also be treated independent of treating occlusive lesions near the vulnerable plaque regions. In another embodiment, a vulnerable plaque treatment drug or biologically active agent may be injected through or around the fibrous cap of a vulnerable plaque. Alternatively, in the event of a thrombotic event, a drug may be injected to prevent complete occlusion of the vessel. In one embodiment, a needle catheter may be used to inject the drug. The needle catheter may be modified to accommodate the following targets around the vulnerable plaque: fibrous cap, proteoglycan-rich surface layer, subintimal lipid core, proximal or distal regions of the plaque, media containing smooth muscle cells around the lipid core, and peri-adventitial space. In another embodiment, the needle catheter may include a sensing capability to determine penetration depth of the needle. Furthermore, the needle catheter may be configured to adopt balloons of various sizes to control the angle of needle penetration. Moreover, the use of balloons would enable accurate penetration of the needle at the desired target.
- In another embodiment, a drug eluting stent may be used to strengthen or increase the thickness of the fibrous cap of the vulnerable plaque in a controlled manner. Increasing the thickness of the fibrous cap may redistribute and lower the stresses in the fibrous cap. This may stabilize the plaque and prevent it from rupturing.
- Referring to
FIG. 4 , adrug delivery stent 450 to treat a vulnerable plaque region is illustrated.Stent 450 is disposed in anarterial lumen 430 to treat bothocclusive plaque 460 andvulnerable plaque 410 located downstream fromocclusive plaque 460. As illustrated,stent 450 releases a drug (indicated by arrows 470) to treat thevulnerable plaque 410. As discussed above, vulnerable plaque regions commonly exist near occlusive plaque, and treating both might be advantageous over separate procedures.Occlusive plaque 460 has grown to cause a narrowing of thearterial lumen 430.Stent 450 is shown in a state before expansion to enlarge the diameter of thearterial lumen 430. A dilation balloon (not shown) may be used to expandstent 450, orstent 450 may be made of a material that self-expands (e.g., Nitinol) so that a dilation balloon is not needed. - As illustrated in
FIG. 4 ,vulnerable plaque 410 is located downstream of theocclusive plaque 460 but does not show any vessel occlusion.Vulnerable plaque 410 hassoft lipid core 415 withfibrous cap 420 separatingvulnerable plaque 410 fromarterial lumen 430. As indicated byarrows 470,stent 450 releases a drug or biologically active agent through the bloodstream ofarterial lumen 430 to treatvulnerable plaque 410. In one embodiment, lipid lowering agents may be released. Lowering of serum LDL cholesterol may lead to a reduction in the amount of cholesterol enteringvulnerable plaque 410, and increases high density lipoprotein (HDL) cholesterol which may contribute to active LDL removal from thevessel wall 425. Animal studies have shown that removal of lipid increases the relative collagen content offibrous cap 420 and could increase the production of collagen, favoring vulnerable plaque stabilization. Lipid lowering animal studies suggest this also treatsvulnerable plaque 410 by reducing local inflammation and the expression and activity of matrix-degrading enzymes, favoring collagen accumulation infibrous cap 420, making it more resistant to rupture. Lipid lowering agents may also change the composition oflipid core 415 to promote plaque stabilization. It is thought that the lipid lowering agents may convert the high concentration of cholesterol esters to insoluble cholesterol monohydrate crystals, resulting in a morestiff lipid core 415 that is more resistant to plaque rupture. Lipid lowering agents include, but are not limited to hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, niacin, bile acid resins, and fibrates. - Examples of doses of agents which may be used with embodiments of the invention, such as a drug delivery stent (i.e., the stent having been loaded with a drug which is eluted/released over time or a needle catheter) are described herein. The particular effective dose may be modified based on therapeutic results, and the following exemplary doses are acceptable initial levels which may be modified based on therapeutic results.
- In an alternative embodiment, antioxidants may be released from
stent 450. The oxidation of LDL cholesterol appears to have negative impact upon vessel processes during atherogenesis. Oxidized LDL binds to cell receptors on macrophages and contributes to foam cell formation. As such, antioxidants, through their inhibition of LDL oxidation, may contribute to plaque stabilization. Antioxidants may also promote plaque stabilization by reducing matrix degradation withinvulnerable plaque 410. Examples of antioxidants include, but are not limited to vitamin E α-tocopherol), vitamin C, and β-carotene supplements. Additionally, HMG CoA reductase inhibitors may also reduce oxidized LDL levels by increasing the total antioxidant capacity of plasma. - Lipid lowering agents such as statins and antioxidants may be administered at a level of about 0.5 mg/kg per day; higher doses (e.g., 5 times higher) appear to inhibit angiogenesis. See Weis et al., Statins Have Biphasic Effects on Angiogenesis, Circulation, 105(6):739-745 (Feb. 12, 2000). This dosage level may be achieved by loading a stent with about 10-600 μg of the statin, where the stent is designed to elute the statin over a period of 8 weeks. In one embodiment, the stent may have a length of 13 mm and a diameter of 3 mm. In one embodiment, the stent may have a drug release rate of 150 μg over 10 hours, or 15 μg per hour. In another embodiment, the stent may have a lower release rate of about 20 μg over 10 hours, over 2 μg per hour. Additionally, a compound called “AGI-1067”, developed by AtheroGenics, Inc. of Alpharetta, Ga., may be loaded onto the stent. AGI-1067 has been shown in studies to have direct anti-atherosclerotic effect on coronary blood vessels, consistent with reversing the progression of coronary artery disease.
- In an alternative embodiment, extracellular matrix synthesis promoters may be released from
stent 450. Reduced collagen content infibrous cap 420 may result from decreased synthesis of extracellular matrix by smooth muscle cells (SMC) and/or increased breakdown by matrix-degrading proteases, thereby leading to thinning and weakening offibrous cap 420, predisposingvulnerable plaque 410 to rupture with hemodynamic or mechanical stresses. - Vascular SMC synthesize both collagenous and noncollagenous portions of the extracellular matrix. Lack of sufficient SMC to secrete and organize the matrix in response to mechanical stress could render
fibrous cap 420 more vulnerable to weakening by extracellular matrix degradation. Atherosclerosis and arterial injury lead to increased synthesis of many matrix components. In contrast, vulnerable plaque, in general, lacks a sufficient quantity of healthy matrix to provide strength to the fibrous cap to prevent rupture. Thus, promotion of SMC proliferation may lead to plaque stabilization. Delivery of cytokines and growth factors may also achieve SMC proliferation. SMC promoters and proliferative agents such as lysophosphatidic acid may be loaded onto a stent for delivery within a vessel. See Adolfsson et al., Lysophosphatidic Acid Stimulates Proliferation of Cultured Smooth Muscle Cells from Human BPH Tissue: Sildenafil and Papaverin Generate Inhibition, Prostate, 51(1):50-8 (Apr. 1, 2002). For example, a SMC promoter may be administered at a level of about 0.5 mg/kg per day to higher doses of about 2.5 mg/kg per day. This dosage level may be achieved by loading a stent with about 10-600 μg of the SMC promoter, where the stent is designed to elute the drug over a period of 8 weeks. In one embodiment, the stent may have a drug release rate of 150 μg over 10 hours, or 15 μg per hour. In another embodiment, the stent may have a lower release rate of about 20 μg over 10 hours, over 2 μg per hour. - In an alternative embodiment, inhibitors of plaque inflammation and extracellular matrix degradation may be released from
stent 450. Increased matrix degrading activity associated with enzymes derived from cells such as vascular SMC, macrophages and T lymphocytes is a common finding in vulnerable plaque. Studies suggest that matrix metalloproteinases (MMPs) are involved in matrix degradation. Plaque stabilization could be achieved through inhibition of extracellular matrix degradation by preventing the accumulation of macrophages and T lymphocytes in the vulnerable plaque or by inhibiting the proteolytic enzyme cascade directly. Possible methods to achieve MMP inhibition include increasing the levels of natural inhibitors (TIMPS) either by exogenous administration of recombinant TIMPs or administrating synthetic inhibitors. Synthetic inhibitors of MMPs, including tretracycline-derived antibiotics, anthracyclines and synthetic peptides may also be used. MMP inhibitors may be themselves antioxidants and statins based on preclinical animal data. Studies have shown MMP inhibitors, such as cerivastatin to significantly reduce tissue levels of both total and active MMP-9 in a concentration-dependent manner. See Nagashima et al., A 3-hydroxy-3-methylglutaryl Coenzyme A Reductase Inhibitor, Cerivastatin, Supresses Production of Matrix Metalloproteinase-9 in Human Abdominal Aortic Aneurysm Wall, J. Vascular Surgery, 36(1);158-63 (July 2002). As with statins as described above, MMP inhibitors may be administered at a level of about 0.5 mg/kg per day to higher doses of about 2.5 mg/kg per day. This dosage level may be achieved by loading a stent with about 10-600 μg of the SMC promoter, where the stent is designed to elute the drug over a period of 8 weeks. In one embodiment, the stent may have a drug release rate of 150 μg over 10 hours, or 15 μg per hour. In another embodiment, the stent may have a lower release rate of about 20 μg over 10 hours, over 2 μg per hour. Additionally, Avasimibe, an ACAT (Acyl-CoA: cholesterol acyltransferase) inhibitor, in the 10 mg/kg range appears to impact MMPs and plaque burden, as well as monocyte adhesion. See Rodriguez and Usher, Anti-atherogenic Effects of the acyl-CoA: Cholesterol Acyltransferase Inhibitor, Avasimibe (CI-1011), in Cultured Primary Human Macrophages, Atherosclerosis, 161(1); 45-54 (March 2002). - Dosages and concentrations described above are exemplary, and other dosages may be applied such that when delivered over a biologically relevant time at the appropriate release rate, gives a biologically relevant concentration. The biologically relevant time may depend on the biologic target but may range from several hours to several weeks with the most important times being from 1 day to 42 days. Dosages may also be determined by conducting preliminary animal studies and generating a dose response curve. Maximum concentration in the dose response curve could be determined by the solubility of a particular compound or agent in the solution and similarly for coating a stent.
- In yet another alternative embodiment, the active agent may induce collateral artery or vessel growth (i.e., angiogenesis or arteriogenesis) near the vulnerable plaque region such that, in the event of a plaque rupture and subsequent occlusive thrombosis, secondary blood paths may bypass the ruptured region and allow for continued blood flow throughout the artery.
FIG. 12 illustrates one embodiment ofarterial section 1200 with collateral vessels that have been induced with an active agent.Collateral vessels arterial section 1200 either temporarily until the occlusion is treated, or permanently to provide greater blood flow. The active agent has been delivered throughdrug delivery stents Primary artery 1230 branches intosections arrows 1205 indicate the direction of blood flow througharterial section 1200.Vulnerable plaque 1210 is disposed withinarterial branch 1232.Stent 1240 induces the growth ofcollateral vessels vulnerable plaque 1210.Collateral vessel 1251 starts upstream (near stent 1240) fromvulnerable plaque 1210 and ends just downstream fromvulnerable plaque 1210.Collateral vessel 1250 starts upstream fromvulnerable plaque 1210 and ends further downstream ofarterial branch 1232.Collateral vessel 1252 starts upstream fromvulnerable plaque 1210 and ends atarterial branch 1233. - Alternatively, collateral vessel growth may be induced from an arterial branch that does not contain a vulnerable plaque.
Stent 1242 carrying an active agent is disposed withinarterial branch 1231 which inducescollateral vessel 1253 fromarterial branch 1231 tobranch 1233. As such,collateral vessel 1253 may provide an alternate pathway for continued blood flow in the eventvulnerable plaque 1210 ruptures. Although therapeutic or biologically active agents for angiogenesis and arteriogenesis have been described above with respect to drug eluting stents, other types of medical devices may be utilized. In one embodiment, for example, needle catheters may be used to deliver agents to induce angiogenesis and/or arteriogenesis. Needle catheters are described in greater detail below with respect toFIGS. 9-10 . - In one embodiment, therapeutic or biologically active agents may be released to induce arteriogenesis or angiogenesis either downstream, or away from the vulnerable plaque to the myocardium. In the event that an occlusive thrombus occurs from a vulnerable plaque, the myocardium perfused by the affected artery may be salvaged. Representative therapeutic or biologically active agents include, but are not limited to, proteins such as vascular endothelial growth factor (VEGF) in any of its multiple isoforms, fibroblast growth factors, monocyte chemoatractant protein 1 (MCP-1), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta) in any of its multiple isoforms, DEL-1, insulin like growth factors (IGF), placental growth factor (PLGF), hepatocyte growth factor (HGF), prostaglandin E1 (PG-E1), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TBF-alpha), granulocyte stimulating growth factor (G-CSF), granulocyte macrophage colony-stimulating growth factor (GM-CSF), angiogenin, follistatin, and proliferin, genes encoding these proteins, cells transfected with these genes, pro-angiogenic peptides such as PR39 and PR11, and pro-angiogenic small molecules such as nicotine. In one embodiment, 10-600 μg of one or a mixture of these agents may be loaded onto a stent for delivery within a vessel. These agents may have a release rate for up to eight weeks. In another embodiment, a stent may be loaded with 300 micrograms of an angiogenic agent with a release rate of eight weeks. Alternatively, a dose may be determined by those skilled in the art by conducting preliminary animal studies and generating a dose response curve. Maximum concentration in the dose response curve would be determined by the solubility of the compound in the solution.
- In using drug eluting stents and related technology to deliver the vulnerable plaque treatment agent (e.g.,
stent 450 ofFIG. 4 ), the active agent may be dispersed or co-dissolved directly in a solution of a matrix such as ethylene vinyl alcohol, ethylene vinyl acetate, poly(hydroxyvalerate), poly (L-lactic acid), poly(D,L-lactic acid), poly(glycolic acid), poly(lactide-co-glycolide) polycaprolactone, polyanhydride, polydiaxanone, polyorthoester, polyamino acids, poly(trimethylene carbobnate), or other suitable synthetic polymers. The polymer may be coated on a stent using dip coating, spin coating, spray coating or other coating methods known in the art. -
FIGS. 5A-5C illustrate the placement ofdrug delivery stent 550 to treat bothocclusive plaque 560 andvulnerable plaque 510 localized downstream fromocclusive plaque 560. In this example,vulnerable plaque 510 is located near a branched region ofarterial lumen 530. In one embodiment,stent 550 is a self-expanding stent, and is disposed neardistal end 542 ofcatheter 540.Catheter 540 is advanced througharterial lumen 530 and positioned nearocclusive plaque 560.Retractable sheath 545 maintainsstent 550 in a crimped and collapsed position so thatstent 550 may be fit withinarterial lumen 530. As illustrated inFIG. 5A , assheath 545 retracts,stent 550 expands and applies physical pressure toocclusive plaque 560. In effect,stent 550 widensarterial lumen 530 that has been narrowed because ofocclusive plaque 560.FIG. 5B illustratesstent 550 in a fully expanded position, allowing normal blood flow througharterial lumen 530. -
Stent 550 may be coated with a drug or biologically active agent that releases from the surface ofstent 550 whensheath 545 retracts andstent 550 becomes exposed to the blood inarterial lumen 530. The flow of the blood througharterial lumen 530 migrates the agent (as indicated by the arrows 570) towardsvulnerable plaque 510. The agent targetsvulnerable plaque 510. In one embodiment, the agent thickens and/or strengthensfibrous cap 520. In doing so, the likelihood offibrous cap 520 rupturing is reduced. In another embodiment, the distribution, size or consistency oflipid core 515 is altered. A combination of agents may be utilized both to thickenfibrous cap 520 and alter the size or consistency oflipid core 515 ofvulnerable plaque 510 to strengthenfibrous cap 520.FIG. 5C illustrates the treatment effects of deployingstent 550.Occlusive plaque 560 has been treated physically by compressing it against the arterial wall.Vulnerable plaque 510 has been treated through strengthening and/or thickeningfibrous cap 520 and the favorable alteration of the size or distribution of thelipid core 515. - A vulnerable plaque treatment agent may be delivered independent of treating occlusive atherosclerosis.
FIG. 6 illustrates a vulnerable plaque treatment agent delivered in the form of a microcapsule ormicroparticle 670. The use ofmicroparticle 670 allows for delivery of a treatment agent in a controlled manner to ensure treatment over a desired period of time. Somemicroparticles 670 possess the characteristic of being degradable at a designated rate. -
Microparticles 670 may also be designed to adhere tovessel wall 635 by blending in orcoating microparticles 670 with materials that promote adhesion tovessel wall 635.Microparticles 670 may be rendered bioadhesive by modifying them with bioadhesive materials such as gelatin, hydroxypropyl methylcellulose, polymethacrylate derivatives, sodium carboxymethycellulose, monomeric cyanoacrylate, polyacrylic acid, chitosan, hyaluronic acid, anhydride oligomers, polyycarbophils, water-insoluble metal oxides and hydroxides, including oxides of calcium, iron, copper and zinc.Microparticles 670 may be modified by adsorbing the bioadhesive material onmicroparticles 670 through ionic interactions, coating the bioadhesive material on the microparticles by dip or spray coating, conjugating the bioadhesive material to thepolymer constituting microparticle 670, or blending in the bioadhesive material into the polymer constituting themicroparticles 670, before themicroparticles 670 are formed. - The particle size of
microcapsules 670 may be less than about 10 microns to prevent possible entrapment in the distal capillary bed.Microparticles 670 may be delivered intra-arterially near the site ofvulnerable plaque 610, and also prophylactically at locations that are proximal and distal to vulnerable plaque 610 (not shown). Upon delivery withinfusion catheter 640,microparticles 670 travel a short distance distally before adhering tovessel wall 630 nearvulnerable plaque 610. The active agent ofmicroparticles 670 is then released over time to thicken and/or strengthenfibrous cap 620, alter the size or distribution oflipid core 615, or both.Microparticles 670 may be delivered withinfusion catheter 640 or any other delivery device known in the art. In one embodiment, infusion catheter may be a needle catheter having one or more injection ports to releasemicroparticles 670. - Suitable polymers for the controlled-
release microparticles 670 include, but are not limited to, poly (L-lactide), poly (D,L-lactide, poly(glycolide), poly lactide-co-glycolide), polycaprolactone, polyanhydride, polydiaxanone, polyorthoesters, polyamino acids, poly (trimethylene carbonate), and combinations thereof. Several methods exist for formingmicroparticles 670, including, but not limited to solvent evaporation, coacervation, spray drying, and cryogenic processing. - In solvent evaporation, the polymer is dissolved in a volatile organic solvent such as methylene chloride. The treatment agent is then added to the polymer solution either as an aqueous solution containing an emulsifying agent such as PVA, or as a solid dispersion, and stirred, homogenized or sonicated to create a primary emulsion of treatment agent in the polymer phase. This emulsion is stirred with an aqueous solution that contains a polymer in the aqueous phase. This emulsion is stirred in excess water, optionally under vacuum to remove the organic solvent and harden the microparticles. The hardened microparticles are collected by filtration or centrifugation and lyophilized.
- The microparticles may also be formed by coacervation. In this method, a primary emulsion of treatment agent in an aqueous phase is formed as in the solvent evaporation method. This emulsion is then stirred with a non-solvent for the polymer, such as silicone oil to extract the organic solvent and form embryonic microparticles of polymer with trapped treatment agent. The non-solvent is then removed by the addition of a volatile second non-solvent such as a heptane, and the microparticles harden. The hardened microparticles are collected by filtration or centrifugation and lyophilized.
- In spray drying, the treatment agent, formulated as lyophilized powder is suspended in a polymer phase consisting of polymer dissolved in a volatile organic solvent such as methylene chloride. The suspension then spray dried to produce polymer microparticles with entrapped treatment agent.
- Microparticles may also be formed by cryogenic processing. In this method, the treatment agent, formulated as lyophilized powder is suspended in a polymer phase consisting of polymer dissolved in a volatile organic solvent such as methylene chloride. The suspension is sprayed into a container containing frozen ethanol overlaid with liquid nitrogen. The system is then warmed to −70° C. to liquefy the ethanol and extract the organic solvent from the microparticles. The hardened microparticles are collected by filtration or centrifugation and lyophilized.
-
FIGS. 13A-13B illustrate cross-sectional views of one embodiment of a drug eluting stent that may be used to increase the thickness or strengthen, in a controlled manner, the fibrous cap near a vulnerable plaque. Strengthening of and increasing the thickness of the fibrous cap may redistribute and lower the stresses in the fibrous cap, effectively stabilizing the plaque and preventing its rupture. -
Cross-sectional views 1300 include lumen 1330 (e.g., an arterial lumen) withlipid core 1315 of a vulnerable plaque andfibrous cap 1320.Stent 1340 having stent struts, for example struts 1342, 1344, is placed withinlumen 1330 nearlipid core 1315 andfibrous cap 1320. In one embodiment of using a drug eluting stent,stent 1340 serves as a vehicle for delivering an appropriate therapeutic or biologically active agent to the site of the vulnerable plaque. Afterstent 1340 has been deployed at a desired location, it may cause platelet deposition, fibrosis and neointimal formation in the stented region. This fibromuscular response may cause the originalfibrous cap 1320 thickness to increase, thereby lowering the stresses in fibrous cap 1320 (as illustrated inFIG. 13B ). This additional hyperplasia, combined with originalfibrous cap 1320 produced bystent 1340 can be thought of as a “neo-cap.”Neo-cap 1360, as illustrated inFIG. 13B , has developed near the inner diameter ofstent 1340. The controlled release of a drug or biologically active agent fromstent 1340 may allow an increase infibrous cap 1320 thickness because of the injury sufficient to stabilizelipid core 1315, but may minimize or prevent excessive restenosis. The type of biologically active agent, the dosage, release rate and the duration of release may influence the growth of neo-cap 1360. Therefore, by controlling these factors the growth of neo-cap 1360 may be controlled. After the thickness offibrous cap 1320 has been increased andlipid core 1315 has been stabilized, the size oflumen 1330 may be increased by balloon angioplasty if necessary. - The biologically active agent used for controlling
fibrous cap 1320 growth may be delivered using a metal stent platform (e.g., stent 1340). The drug may be released through a polymer membrane-matrix system that is deposited on the surface of the stent. Polymers such as EVAL can be used for the membrane-matrix system. Several choices of metals are available for making the stent, including but not limited to, stainless steel, cobalt-chromium alloy and shape-memory alloys such as Nitinol. Depending on the design of the stent and delivery system, it may be possible to direct the biologically active agent to act in specific locations of interest in the vulnerable plaque. For example, biologically active agents which are anti-inflammatory in nature may be optimally delivered into or around the plaque shoulder regions, a site of inflammatory cell accumulation where the lipid core edges meet the normal wall opposite the vulnerable plaque. Conversely, it may be possible to direct the biologically active agent away from specific locations of interest in the vulnerable plaque. For example, biologically active agents which are anti-restenotic, such as Actinomyocin-D, may be directed to act away from the expected regions of high stress infibrous cap 1320, which coverlipid core 1315 in general. These regions would be the shoulder regions or the portion offibrous cap 1320 centered circumferentially alonglipid core 1315 edge nearestlumen 1330. And finally, it may also be possible to designstent 1340 or other types of delivery systems that selectively diffuse a biologically active agent appropriately, by leveraging throughstent 1340 design the stress-assisted diffusion properties at the stent-plaque interface in these select regions. - The biologically active agent may also be delivered using a biodegradable polymeric stent. In this case, after the biologically active agent has eluted from the stent, the stent degrades within a certain period of time leaving behind a stabilized plaque. The polymers available for making the stent include poly-L-lactide, polyglycolic/poly-L-lactic acid (PGLA), Poly-L-latic acid (PLLA), poly-L-lactide, polycaprolactone (PCL), poly-(hydroxybutyrate/hydroxyvalerate) copolymer (PHBV) or shape memory polymers such as a compound of oligo(e-caprolactone) dimethacrylate and n-butylacrylate.
- Examples of therapeutic or biologically active agents include but are not limited to rapamycin, actinomycin D (ActD) and their derivatives, antiproliferative substances, antineoplatic, antinflammatory, antiplatelet, anticoagulant, antifebrin, antithrombin, antimitotic, antibiotic and antioxidant substances. Examples of antineoplastics include taxol (paclitaxel and docetaxel). Examples of antiplatelets, anticoagulants, antifibrins and antithrombins include sodium heparin, low molecular weight heparin, hirudin, IIb/IIIa platelet membrane receptor antagonist and recombinant hirudin. Examples of antimitotic agents include methotrexate, azathioprine, vincristine, vinblastine, fluororacil, adriamycin and mutamycin. Examples of cytostatic or antiproliferative agents include angiopeptin, calcium channel blockers (such as Nifedipine), Lovastatin (an inhibitor of HMG-CoA reductase, a cholestrol lowering drug from Merck). Other therapeutic or biologically active agents which may be utilized include alpha-interferon, genetically engineered epithelial cells and dexamethasone. Dosages comparable to that described above with respect to drug eluting stents may be used.
- Stent Grafts
- In one embodiment, a stent graft may be used for the treatment of vulnerable plaque. The stent graft may have a thin, expandable polytetrafluoroethylene (ePTFE) cylindrical tube affixed to an inner surface of a self-expandable stent. The inner surface of the ePTFE tube may have a layer of endothelial cells. The endothelial cells, when dispersed near the vulnerable plaque region, may promote cell migration to form a fully lined monolayer on the lumen surface. The stent graft may also shield existing vulnerable plaque from the possibility of an acute, thrombotic event. If the plaque ruptures, a cascade of blood-vessel wall interactions occurs, resulting in thrombosis and ultimately partial or total arterial occlusion. Therefore, shielding vulnerable plaque from the vessel lumen would eliminate the possibility of plaque contents being exposed to blood flow in case of rupture. In addition, the stent graft may provide reinforcement to the fibrous cap and reduce any physical stress placed on it due to the size of the lipid core.
-
FIG. 7 illustrates another embodiment for treating vulnerable plaque in whichstent graft 750 is deployed nearvulnerable plaque 710.Stent graft 750 has a thin expandable polytetrafluoroethylene (ePTFE)cylindrical tube 754 affixed toinner surface 751 of self-expandable stent 752.Inner surface 755 ofePTFE tube 754 has a layer ofendothelial cells 756. The layer ofendothelial cells 756 promotes cell migration that eventually forms a complete monolayer on the surface ofarterial lumen 730. As such,stent graft 750 shields existingvulnerable plaque 710 from an occlusive thrombosis event. Moreover,stent graft 750 may provide reinforcement tofibrous cap 720 and reduce any increased physical stress placed on it in vivo due tolipid core 715 presence or other hemodynamic forces. -
ePTFE tube 754 serves as a physical barrier betweenvulnerable plaque 710 andarterial lumen 730. BecauseePTFE lumen surface 755 acts as an arterial equivalent,ePTFE tube 754 should remain free from occlusion. In one embodiment, theePTFE tube 754 is made anti-thrombotic by surface treatment. The surface ofePTFE tube 754 may be made anti-thrombotic for use as a vascular graft by seedingsurface 755 withendothelial cells 756.Endothelial cells 756 seeded within vascular grafts have been shown to promote cell migration that eventually form a fully lined monolayer on a lumen surface. - Several approaches exist to seed
stent graft 750 withendothelial cells 756. In one embodiment, a pressurized sodding technique may be used in whichePTFE tube 754 is expanded to 5 psi using media that contain endothelial cells.Endothelial cells 756 are isolated from the canine falciform ligament fat. Endothelial cells may also be isolated from human liposuction fat micro-vessel, umbilical veins, and other comparable sources. -
Stent graft 750 may be disposed near a targetvulnerable plaque 710 in a manner similar to that of adrug eluting stent FIGS. 4 and 5 A-5C).Stent graft 750 is disposed near a distal end of a catheter (not shown). The catheter is passed througharterial lumen 730 so thatstent graft 750 is positioned nearvulnerable plaque 710. A retractable sheath (not shown) maintains the stent graft in a crimped position so that the stent graft may be advanced withinarterial lumen 730. As illustrated inFIG. 7 ,stent graft 750 expands and applies physical pressure tofibrous cap 720 surroundingvulnerable plaque 710.FIG. 7 illustratesstent graft 750 in a fully expanded position, allowing normal blood flow througharterial lumen 730. -
FIGS. 8A-8B illustrate cross-sectional views ofstent graft 850 havinginner tube 854 lined withendothelial cells 856 for treating vulnerable plaque. A self-expandable stent 852 is used as structural support to keepstent graft 850 secured in place withinarterial lumen 730. A self-expandable stent may be advantageous over a balloon expandable stent. A self-expandable stent does not require an internal lumen pressure to expand, and so anyseeded cells 856 are kept intact. In contrast, a balloon expandable stent could damagecells 856 ofstent graft 850 when expanded. The self-expandingstent 852 may be made from a shape memory alloy such as NiTi (e.g., Nitinol). In order to provide additional flexibility tostent 852, stent links (e.g., 860, 861) may be eliminated fromstent 852. In an alternative embodiment,stent 852 may have a series of shape memory metallic rings (not shown) bonded to the outer surface ofePTFE tubing 854. - Various techniques are available to bond
ePTFE tube 854 tostent 852. For example, to bond the ePTFE tube to the metal, a primer is first applied to the metallic portions (e.g., 860, 861) ofstent 852. These rings are then inserted overePTFE tube 854. Silicon adhesive is used to bondmetallic rings ePTFE tubing 854. The stent graft is cured at about 150° C. for approximately 15 minutes. The silicon adhesive seeps through the ePTFE tube matrix and after curing acts as a medium that mechanically fastens the ePTFE tube to the metal. The inner surface of the polymeric tube is then seeded with endothelial cells. - In addition to the shape memory alloys, stent rings 860, 861 may also be made from shape memory polymers. Various shape memory polymers with great potential for biomedical applications are currently in the research phase. For example oligo(e-caprolactone) dimethacrylate and n-butyl acrylate are two monomeric compounds that, when combined, generate a family of polymers that exhibit excellent shape memory characteristics. The oligo(e-caprolactone) dimethacrylate furnishes the crystallizable “switching” segment (characteristic of shape memory materials) that determines both the temporary and permanent shape of the polymer. By varying the amount of the comonomer, n-butyl acrylate, in the polymer network, the cross-link density can be adjusted. This allows the mechanical strength and transition temperature of the polymers to be tailored over a wide range. Therefore, the stent incorporating these polymers can be deployed using their shape memory characteristics. Furthermore, other polymers such as polyurethane and ultra high molecular weight polyethylene (UHMWPE) can also be used for tubing used in the stent graft.
- In an alternative embodiment,
stent graft 850 may also be used as an apparatus for local drug delivery.Stent graft 850 may be loaded with anti-restenotic, anti-thrombotic, or other vulnerable plaque treatment agents (e.g., as discussed above with respect toFIGS. 4 and 5 A-5C). Furthermore, in yet another alternative embodiment,stent graft 850 may be radioactively enhanced or incorporated with a material that generates a magnetic susceptibility artifact ofstent graft 850. - Needle Catheter
- In another embodiment, a vulnerable plaque treatment drug or biologically active agent may be injected through or around a vulnerable plaque region. In one embodiment, a needle catheter may be used to inject the biologically active agent. The needle catheter may be adjusted to penetrate various targets around the vulnerable plaque including, but not limited to: fibrous cap, proteoglycan-rich surface layer, subintimal lipid core, proximal or distal regions of the vulnerable plaque, media containing smooth muscle cells around the lipid core, and the periadventitial space.
- In an alternative embodiment, the needle catheter may include sensing capabilities to determine the depth of penetration of the needle, as well as dial-in needle extension. Furthermore, different angle balloons may be added in order to use case-specific ramp angle to penetrate into the vulnerable plaque region while positioning the needle catheter below the actual occlusion. The needle catheter may be placed proximal or distal to the vulnerable plaque region because studies have shown cell localization, activity, and apoptosis have preferential occurrence in the upstream or downstream parts of vulnerable plaque regions.
-
FIG. 9A illustrates a cross-sectional view of one embodiment ofneedle catheter 950 that may be used to inject a vulnerable plaque treatment agent intoarterial wall 980 nearvulnerable plaque 910.Vulnerable plaque 910 has developed withinarterial wall 980, separated fromarterial lumen 930 byfibrous cap 920.Distal end 941 ofcatheter 940 hasinflatable balloon 948 with at least oneneedle lumen 945 extending fromdistal end 941 ofcatheter 940 alongproximal end 947 ofballoon 948.Retractable needle 945 extends fromneedle lumen 942 and penetratesarterial wall 980.Inflated balloon 948 securesneedle catheter 950 at a target location. Moreover, becauseneedle sheath 942 is coupled alongproximal end 947 ofballoon 948,inflated balloon 948 provides a penetration angle forneedle 945.Needle catheter 950, as illustrated, has twoneedles distal end 941 ofcatheter 950. Any number of needles may be utilized withneedle catheter 950. For example, in an alternative embodiment, the needle catheter may have only one needle for injecting a vulnerable plaque treatment agent. - As illustrated,
needle catheter 950targets lipid core 915 ofvulnerable plaque 910 directly. In one embodiment, a lipid lowering agent may be injected intovulnerable plaque 910, or agents which could change lipid core properties could be injected. PEG with an aldehyde/gluteraldehyde mix may be injected intolipid core 915 potentially cross-linkingvulnerable plaque 910 components to inhibit erosion, rupture, or other forms of destabilization. Other vulnerable plaque treatment agents may be used, including antioxidants, and extracellular matrix synthesis promoters (e.g., as discussed with respect toFIGS. 4 and 5 A-5C). -
Needle catheter 950 may also be configured to include a feedback sensor (not shown) for mapping the penetration depth ofneedles fibrous cap 920 or media 984 ofarterial wall 980. Alternatively, it may be desirable to inject a drug intolipid core 915, or adventitia 986. - In use,
distal end 941 ofneedle catheter 950 is inserted into the lumen of a patient and guided to a vulnerable plaque region. As illustrated inFIG. 9A ,distal end 941 ofneedle catheter 950 is positioned near aproximal end 912 ofvulnerable plaque 910. Alternatively,needle catheter 950 may be positioned near adistal end 914 ofvulnerable plaque 910.Vulnerable plaque 910 may be detected using the sensor (not shown) disposed onneedle catheter 950. By utilizing a sensor, the injection site for treatingvulnerable plaque 910 may be precisely identified. -
FIGS. 10A and 10B illustrate cross sectional views of one embodiment of a needle catheter for injecting a vulnerable plaque treatment drug or biological agent.FIG. 10 illustratesneedle catheter 1001 with sensing capabilities having elongatedcatheter body 1010 that surroundsneedle lumen 1012 andinner lumen 1014. Housed withininner lumen 1014 arefluid lumen 1016 andinner member 1018 that also containsguide wire 1020,guide wire lumen 1022, andultrasonic element lumen 1024.Inflatable balloon 1026 is coupled toinner lumen 1014 and theinner member 1018.Proximal end 1028 ofballoon 1026 is coupled todistal end 1030 ofinner lumen 1014 anddistal end 1032 ofballoon 1026 is coupled todistal end 1036 ofinner member 1018. - In an alternative embodiment, both
guide wire 1022 and retractableultrasonic element 1034 may be housed withininner member 1014.Elongate body 1010 surroundsinner member 1014 andneedle lumen 1012. Housed withininner lumen 1014 areinner member 1018 andfluid lumen 1016.Inner member 1018 surroundsguide wire 1022 and retractableultrasonic element 1034.Inflatable balloon 1026 is coupled toinner lumen 1014 andinner member 1018.Proximal end 1028 ofballoon 1026 is coupled todistal end 1030 ofinner lumen 1014 anddistal end 1032 ofballoon 1026 is coupled todistal end 1036 ofinner member 1018. - The
ultrasonic element lumen 1024 ofinner member 1018 houses retractableultrasonic element 1034. The distal end of the ultrasonic element has an ultrasound transducer or transducer array and the proximal end contains the associated co-axial cable that connects to an imaging display system (not shown). Ultrasonic waves generated by the ultrasonic element impinge on the surface of a vulnerable plaque or vulnerable plaque region. The timing/intensity of the ultrasonic waves reflected back to the transducer differentiates between the various anatomic boundaries or structures of the vulnerable plaque region, for example, the various layers of an arterial wall. The waves detected by the transducer are converted to electric signals that travel along the coaxial cable to the imaging system. The electrical signals are processed and eventually arranged as vectors based on the digitized data. In one embodiment, the ultrasound transducer has piezoelectric crystal configured for optimal acoustic output efficiency and energy conversion. In alternative embodiments, the crystal is made of PZT or lead-ceramic materials such as PbTiO3 (lead titanate) or PbZrO3 (lead zirconate). - As further illustrated in
FIGS. 10A-10B ,retractable needle 1013 is housed inneedle lumen 1012 and freely movable therein. The hollow, tubular shapedneedle 1013, having an inner diameter within a range of approximately 0.002 inch to 0.010 inch (5.1×10−3 cm to 25.4×10−3 cm) and an outer diameter within the range of approximately 0.004 inch to 0.012 inch (10.2×10−3 cm to 30.5×10−3 cm), provides a fluid channel that extends fromproximal end 1040 todistal end 1042 ofneedle 1013.Distal end 1042 ofneedle 1013 has a curved tip. In one embodiment,needle 1013 has an angle of curvature of about 30 degrees to 90 degrees. The curvature ofneedle 1013 facilitates placement of the needle tip near or within a desired target of a vulnerable plaque region.Needle 1013 may be formed from a variety of metals including, but not limited to stainless steel, NiTi (nickel titanium) (e.g., Nitinol) or other comparable semi-rigid materials. -
Proximal end 1040 ofneedle 1013 is coupled toadapter 1050 that couples needle 1013 toneedle lock 1052 andneedle adjustment knob 1054.Needle lock 1052 is used to secureneedle 1013 in place and prevent further movement ofneedle 1013 within an arterial lumen onceneedle 1013 is placed in the target position.Needle adjustment knob 1054 controls accurate needle extension out of the distal end of the catheter and depth of penetration into the vulnerable plaque region. As such, movement ofneedle adjustment knob 1054 moves needle 1013 in and out ofneedle lumen 1012. Onceneedle 1013 has penetrated a target to a desired depth,needle lock 1052 enablesneedle 1013 to be secured in place thereby preventing any movement ofneedle 1013 withinneedle lumen 1012. - A
drug injection port 1060 is disposed nearproximal end 1062 ofneedle catheter 1001.Drug injection port 1060 couples needlecatheter 1001 with various dispensing devices such as a syringe or fluid pump. Fluids injected intodrug injection port 1060 travel throughneedle 1013 and are dispensed from the distal tip ofneedle 1013. -
FIGS. 9B-9D illustrate embodiments ofneedle catheter 950 targeting various regions near a vulnerable plaque for injection of a vulnerable plaque treatment agent. As discussed above,needle catheter 950 may have a feedback sensor (e.g.,ultrasonic element 1034 ofFIG. 10B ) to determine and control a penetration depth forneedles needle catheter 950 may inject a vulnerable plaque stabilizing drug or biologically active agent intofibrous cap 920 as illustrated inFIG. 9B , regions within thesubintimal space 982 ofarterial wall 980 as illustrated inFIG. 9C , or regions distal tovulnerable plaque 910 as illustrated inFIG. 9D . - For example, with respect to
FIG. 9B antioxidants such as reactive oxygen scavengers (ROS), vitamin C and E may be injected intofibrous cap 920. The oxidant acts as a matrix-ase inhibitor to prevent significant collagen degradation withinfibrous cap 920. - In another embodiment,
needle catheter 950 may also be used as part of a biological or gene therapy method to treatvulnerable plaque 910. For example, upregulators of tissue inhibitors of metalloproteinases (TIMPS) may be injected into adventitia 986. TIMPS are expressed by surrounding smooth muscle cells to downregulate MMP production. Alternatively, recombinant TF pathway inhibitors (TFPI) may one day be injected intolipid core 915 to inhibit thrombosis due to erosion, rupture or other forms of plaque destabilization. - In yet another embodiment,
needle catheter 950 may be used to deliver an agent to induce angiogenesis and/or arteriogenesis as described above with respect toFIG. 12 . The therapeutic angiogenesis agents and drugs discussed above may be injected near a treatment site as an alternative to delivery by a drug eluting stent. -
FIGS. 11A-11D illustrate flowcharts describing methods for stabilizing vulnerable plaque. The methods described with respect toFIGS. 11A-11D include detecting vulnerable plaque. Various techniques may be utilized to detect the presence and location of vulnerable plaque. For example, an ultrasound probe (IVUS) or an optical coherence tomography probe (OCT) may be guided through the arteries to scan for vulnerable plaque. Alternatively, magnetic resonance imaging (MRI) devices may be able to detect vulnerable plaque. Near Infrared spectroscopy is another technique for detecting vulnerable plaque. For example, certain wavelengths of light penetrate the arterial wall and produce a specific chemical signature that could correlate to vulnerable plaque composition. Additionally, thermography may also be used to detect vulnerable plaque. Plaques that rupture tend to be inflamed, and data indicates this correlates to a higher temperature compared to non-vulnerable type plaques that do not rupture. As such, a temperature sensitive probe that measures the temperature of arteries could indicate the presence of vulnerable plaque. Alternatively, liquid crystal thermography methods may also be used. For example, a balloon material made of a thermochromic liquid crystal material may be able to optically detect property changes when exposed to increases in temperature. When the balloon contacts a vulnerable plaque, the higher temperature of the vulnerable plaque may be detected by analyzing a beam of light directed towards the suspected vulnerable plaque region and the balloon material in contact therewith. The light may undergo a color change in the balloon material as a result of the higher temperature. -
FIG. 11A describes a method to treat vulnerable plaque downstream from an occlusive plaque. The occlusive plaque may be treated with a stent or balloon catheter. The vulnerable plaque may be treated by altering the lipid core and/or strengthening or thickening the fibrous cap surrounding the vulnerable plaque. The vulnerable plaque is first detected by any one of the techniques described above, including but not limited to IVUS, OCT, MRI, near infrared spectroscopy, thermography, and liquid crystal thermography. The vulnerable plaque may be downstream from an occlusive plaque that has been detected, for example, with an angiogram. A drug delivery catheter is provided having a vulnerable plaque stabilizing agent. In one embodiment, the drug delivery catheter may deploy a drug eluting stent. The drug eluting stent is positioned at the occlusive plaque to widen the arterial lumen whose blood flow has been impeded by the plaque. The vulnerable plaque stabilizing agent is released towards a vulnerable plaque region located downstream from the release site. Alternatively, the agents may be in the form of microparticles to control the release of the agents over time. The agents released from the drug delivery catheter may include lipid lowering agents, antioxidants, extracellular matrix synthesis promoters, or inhibitors of plaque inflammation and extracellular degradation. -
FIG. 1B describes a method to treat vulnerable plaque by inducing collateral artery or vessel growth to the myocardium downstream from or adjacent to an occlusive plaque. The occlusive plaque may be treated with a stent or balloon catheter. By inducing therapeutic angiogenesis (e.g., collateral artery or vessel growth), blood flow is maintained in case a vulnerable plaque ruptures leading to an occlusive thrombosis. The vulnerable plaque is first detected by any one of the techniques described above, including but not limited to IVUS, OCT, MRI, near infrared spectroscopy, thermography, and liquid crystal thermography. The vulnerable plaque may be downstream from an occlusive plaque that has been detected, for example, with an angiogram. - A drug delivery catheter or stent is provided having an agent that induces collateral artery or vessel growth. In one embodiment, the drug delivery catheter may deploy a drug eluting stent. The drug eluting stent is positioned at the occlusive plaque to widen the arterial lumen whose blood flow has been impeded by the plaque. The agent to induce collateral artery or vessel growth is released towards a vulnerable plaque region located downstream from the drug release site. Representative therapeutic or biologically active agents include, but are not limited to, proteins such as vascular endothelial growth factor (VEGF) in any of its multiple isoforms, fibroblast growth factors, monocyte chemoatractant protein 1 (MCP-1), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta) in any of its multiple isoforms, DEL-1, insulin like growth factors (IGF), placental growth factor (PLGF), hepatocyte growth factor (HGF), prostaglandin E1 (PG-E1), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TBF-alpha), granulocyte stimulating growth factor (G-CSF), granulocyte macrophage colony-stimulating growth factor (GM-CSF), angiogenin, follistatin, and proliferin, genes encoding these proteins, cells transfected with these genes, pro-angiogenic peptides such as PR39 and PR11, and pro-angiogenic small molecules such as nicotine.
-
FIG. 11C describes a method to treat vulnerable plaque by implanting a stent graft on the arterial wall near a vulnerable plaque. This method of vulnerable plaque stabilization may be performed independent of treating an occlusive plaque. The vulnerable plaque is first detected by any one of the techniques described above, including but not limited to IVUS, OCT, MRI, near infrared spectroscopy, thermography, and liquid crystal thermography. The stent graft is disposed near a distal end of a catheter and advanced within the arterial lumen and positioned near a vulnerable plaque. Retracting a sheath covering the stent graft deploys the stent graft. In one embodiment, the stent graft has a thin ePTFE cylindrical tube affixed to the inner surface of a self-expandable stent. The inner surface of the stent has a layer of endothelial cells. The layer of endothelial cells promote cell migration that forms a fully lined monolayer on the arterial lumen surface. As such, the stent graft shields existing vulnerable plaque from an occlusive thrombotic event. Moreover, the stent graft provides reinforcement to the fibrous cap and reduces any physical stress placed on it due to the presence of the lipid core and hemodynamic forces. -
FIG. 11D describes another method to treat vulnerable plaque. The vulnerable plaque may be treated by injecting a stabilizing drug or biologically active agent at various locations within and around the vulnerable plaque. The vulnerable plaque is first detected by any one of the techniques described above, including but not limited to IVUS, OCT, MRI, near infrared spectroscopy, thermography, and liquid crystal thermography. A needle catheter is advanced through an arterial lumen and positioned near a proximal end of the vulnerable plaque. Alternatively, the needle catheter may be positioned at or near a distal end of the vulnerable plaque. A sensor disposed on the needle catheter determines a penetration depth for the needle catheter. The needle catheter may be adjusted to penetrate various targets around the vulnerable plaque including, but not limited to: fibrous cap, proteoglycan-rich surface layer, subintimal lipid core, proximal or distal regions of the vulnerable plaque, media containing smooth muscle cells above the lipid core and the adventitial space. The agents released from the drug delivery catheter may include lipid lowering agents, antioxidants, extracellular matrix synthesis promoters, inhibitors of plaque inflammation and extracellular degradation. - In the foregoing specification, the invention has been described with reference to specific exemplary embodiments thereof. It will, however, be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention as set forth in the appended claims. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.
Claims (41)
1. An apparatus, comprising:
an elongated catheter body adapted for insertion in a body lumen; and
a drug delivery device coupled near a distal portion of said elongated body, said drug delivery device configured to deliver a biologically active agent to stabilize a vulnerable plaque.
2. The apparatus of claim 1 , wherein said drug delivery device comprises:
a balloon disposed at a distal end of said drug delivery device; and
at least one needle housed within said drug delivery device, wherein said at least one needle is moveable from a retracted position to an extended position, and wherein an angle of needle penetration relative to said elongated catheter body corresponds to an inflation of said balloon.
3. The apparatus of claim 2 , further comprising a sensor near said distal portion of said catheter, wherein said sensor determines a penetration depth of said at least one needle.
4. The apparatus of claim 1 , wherein said biologically active agent comprises lipid lowering agents.
5. The apparatus of claim 1 , wherein said biologically active agent comprises antioxidants.
6. The apparatus of claim 1 , wherein said biologically active agent comprises anti-inflammatory agents.
7. The apparatus of claim 1 , wherein said biologically active agent comprises extracellular matrix synthesis promoters.
8. The apparatus of claim 1 , wherein said drug delivery device delivers up to 600 μg of said biologically active agent.
9. A method for stabilizing a vulnerable plaque in a lumen wall, comprising:
detecting said vulnerable plaque;
advancing a needle catheter near said vulnerable plaque; and
delivering a vulnerable plaque stabilizing agent with said needle catheter near said vulnerable plaque.
10. The method of claim 9 , further comprising determining a penetration depth of said needle catheter.
11. (canceled)
12. The method of claim 9 , wherein delivering said vulnerable plaque stabilizing drug comprises targeting an intimal layer near said vulnerable plaque.
13. The method of claim 9 , wherein delivering said vulnerable plaque stabilizing drug comprises targeting an adventitial layer near said vulnerable plaque.
14. The method of claim 9 , wherein delivering said vulnerable plaque stabilizing drug comprises targeting a media layer near said vulnerable plaque.
15. The method of claim 9 , wherein delivering said vulnerable plaque stabilizing drug comprises targeting said lipid core of said vulnerable plaque region.
16. The method of claim 15 , wherein targeting said lipid core comprises delivering a cross-linking agent.
17. A method of claim 15 , wherein targeting said lipid core comprises delivering a matrix-ase inhibitor.
18. The method of claim 13 , wherein targeting said adventitial layer comprises delivering a collagen synthesis promoter.
19. The method of claim 13 , wherein targeting said adventitial layer comprises gene therapy.
20. The method of claim 13 , wherein targeting said adventitial layer comprises inserting said needle into said body lumen wall at a point proximal to said vulnerable plaque region, and extending said needle to said adventitial layer.
21. The method of claim 14 , wherein targeting said media layer comprises inserting said needle into said body lumen wall at a point proximal to said vulnerable plaque region, and extending said needle to said media layer.
22. (canceled)
23. The method of claim 15 , wherein targeting said lipid core comprises inserting said needle into said body lumen wall at a point proximal to said lipid core, and extending said needle to said lipid core.
24. The method of claim 9 , wherein said vulnerable plaque stabilizing agent strengthens said fibrous cap.
25. The method of claim 9 , wherein said vulnerable plaque stabilizing agent reduces a size of a lipid core of said vulnerable plaque.
26. The method of claim 9 , wherein said vulnerable plaque stabilizing agent thickens said fibrous cap.
27. A method for treating a vulnerable plaque, comprising:
advancing a medical device within a body lumen; and
delivering a biologically active agent from said medical device, wherein said biologically active agent induces a therapeutic angiogensesis growth away from said vulnerable plaque to maintain a blood perfusion in the event of an occlusive thrombosis from a rupturing of said vulnerable plaque.
28. The method of claim 27 , wherein delivering comprises releasing said biologically active agent upstream from said vulnerable plaque.
29. A method of claim 28 , further comprising providing a drug delivery catheter to release said biologically active agent.
30. The method claim 27 , wherein delivering comprises releasing said biologically active agent through a bloodstream near said vulnerable plaque.
31. The method claim 27 , wherein delivering comprises releasing said biologically active agent towards a lumen wall near said vulnerable plaque.
32. The method claim 27 , wherein delivering comprises sustained-releasing said biologically active agent.
33. The method of claim 32 , wherein sustained-releasing said biologically active agent comprises releasing said biologically active agent over a period up to about 6 months.
34. The method of claim 29 , wherein said drug delivery catheter comprises dip coating a drug eluting stent with said biologically active agent.
35. The method of claim 29 , wherein said drug delivery catheter comprises spin coating a drug eluting stent with said biologically active agent.
36. The method of claim 31 , wherein releasing said biologically active agent towards said lumen wall comprises adhering a plurality of micro-particles to said lumen wall.
37. The method of claim 27 , wherein said biologically active agent is selected from a group consisting of vascular endothelial growth factor (VEGF), fibroblast growth factors, monocyte chemoatractant protein 1 (MCP-1), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta, DEL-1, insulin like growth factors (IGF), placental growth factor (PLGF), hepatocyte growth factor (HGF), prostaglandin E1 (PG-E1), prostaglandin E2 (PG-E2), tumor necrosis factor alpha (TBF-alpha), granulocyte stimulating growth factor (G-CSF), granulocyte macrophage colony-stimulating growth factor (GM-CSF), angiogenin, follistatin, proliferin, pro-angiogenic peptides, and pro-angiogenic small molecules.
38. The method of claim 27 , wherein delivering said biologically active agent induces a therapeutic angiogenesis growth to a myocardium.
39. The method of claim 27 , wherein delivering said biologically active agent comprises delivering up to 600 μg of said biologically active agent.
40. An apparatus for stabilizing a vulnerable plaque in a lumen wall, comprising:
means for detecting said vulnerable plaque;
means for advancing a needle catheter near said vulnerable plaque; and
means for delivering a vulnerable plaque stabilizing agent with said needle catheter near said vulnerable plaque, wherein said vulnerable plaque stabilizing agent increases a thickness of a fibrous cap.
41. An apparatus for treating a vulnerable plaque, comprising:
means for advancing a medical device within a body lumen; and
means for delivering a biologically active agent from said medical device, wherein said biologically active agent induces a therapeutic angiogenesis growth away from said vulnerable plaque to maintain a blood perfusion in the event of an occlusive thrombosis from a rupturing of said vulnerable plaque.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/283,032 US20060135943A1 (en) | 2002-09-30 | 2005-11-17 | Method and apparatus for treating vulnerable plaque |
US11/388,355 US20060265043A1 (en) | 2002-09-30 | 2006-03-24 | Method and apparatus for treating vulnerable plaque |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/262,151 US7008411B1 (en) | 2002-09-30 | 2002-09-30 | Method and apparatus for treating vulnerable plaque |
US11/283,032 US20060135943A1 (en) | 2002-09-30 | 2005-11-17 | Method and apparatus for treating vulnerable plaque |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/262,151 Division US7008411B1 (en) | 2002-09-30 | 2002-09-30 | Method and apparatus for treating vulnerable plaque |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/388,355 Continuation-In-Part US20060265043A1 (en) | 2002-09-30 | 2006-03-24 | Method and apparatus for treating vulnerable plaque |
Publications (1)
Publication Number | Publication Date |
---|---|
US20060135943A1 true US20060135943A1 (en) | 2006-06-22 |
Family
ID=35966178
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/262,151 Expired - Lifetime US7008411B1 (en) | 2002-09-30 | 2002-09-30 | Method and apparatus for treating vulnerable plaque |
US11/283,032 Abandoned US20060135943A1 (en) | 2002-09-30 | 2005-11-17 | Method and apparatus for treating vulnerable plaque |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/262,151 Expired - Lifetime US7008411B1 (en) | 2002-09-30 | 2002-09-30 | Method and apparatus for treating vulnerable plaque |
Country Status (1)
Country | Link |
---|---|
US (2) | US7008411B1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090118700A1 (en) * | 2007-11-07 | 2009-05-07 | Callas Peter L | Method for treating coronary vessels |
US20090254051A1 (en) * | 2007-12-06 | 2009-10-08 | Abbott Laboratories | Device and method for treating vulnerable plaque |
US20090291111A1 (en) * | 2008-05-21 | 2009-11-26 | Florencia Lim | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
US20090306120A1 (en) * | 2007-10-23 | 2009-12-10 | Florencia Lim | Terpolymers containing lactide and glycolide |
WO2010065026A3 (en) * | 2007-10-03 | 2010-08-19 | The General Hospital Corporation | Photochemical tissue bonding |
US7862605B2 (en) | 1995-06-07 | 2011-01-04 | Med Institute, Inc. | Coated implantable medical device |
CN106725249A (en) * | 2017-01-04 | 2017-05-31 | 许娟 | Accurate medicine equipment |
US9848906B1 (en) | 2017-06-20 | 2017-12-26 | Joe Michael Eskridge | Stent retriever having an expandable fragment guard |
Families Citing this family (91)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6786900B2 (en) * | 2001-08-13 | 2004-09-07 | Cryovascular Systems, Inc. | Cryotherapy methods for treating vessel dissections and side branch occlusion |
US8608661B1 (en) | 2001-11-30 | 2013-12-17 | Advanced Cardiovascular Systems, Inc. | Method for intravascular delivery of a treatment agent beyond a blood vessel wall |
US10441747B2 (en) * | 2002-01-22 | 2019-10-15 | Mercator Medsystems, Inc. | Methods and systems for inhibiting vascular inflammation |
US7361368B2 (en) | 2002-06-28 | 2008-04-22 | Advanced Cardiovascular Systems, Inc. | Device and method for combining a treatment agent and a gel |
US6855124B1 (en) * | 2002-10-02 | 2005-02-15 | Advanced Cardiovascular Systems, Inc. | Flexible polymer needle catheter |
US8038991B1 (en) | 2003-04-15 | 2011-10-18 | Abbott Cardiovascular Systems Inc. | High-viscosity hyaluronic acid compositions to treat myocardial conditions |
US8821473B2 (en) * | 2003-04-15 | 2014-09-02 | Abbott Cardiovascular Systems Inc. | Methods and compositions to treat myocardial conditions |
US8383158B2 (en) | 2003-04-15 | 2013-02-26 | Abbott Cardiovascular Systems Inc. | Methods and compositions to treat myocardial conditions |
US20050260157A1 (en) * | 2003-09-16 | 2005-11-24 | Medtronic Vascular, Inc. | Method and agent for treating vulnerable plaque |
US7377939B2 (en) * | 2003-11-19 | 2008-05-27 | Synecor, Llc | Highly convertible endolumenal prostheses and methods of manufacture |
US7349971B2 (en) * | 2004-02-05 | 2008-03-25 | Scenera Technologies, Llc | System for transmitting data utilizing multiple communication applications simultaneously in response to user request without specifying recipient's communication information |
US20050228473A1 (en) * | 2004-04-05 | 2005-10-13 | David Brown | Device and method for delivering a treatment to an artery |
EP1755574A4 (en) * | 2004-04-06 | 2009-05-13 | Semafore Pharmaceuticals Inc | Pten inhibitors |
US20050287184A1 (en) * | 2004-06-29 | 2005-12-29 | Hossainy Syed F A | Drug-delivery stent formulations for restenosis and vulnerable plaque |
WO2007001448A2 (en) * | 2004-11-04 | 2007-01-04 | Massachusetts Institute Of Technology | Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals |
US7846147B2 (en) * | 2004-11-18 | 2010-12-07 | Advanced Cardiovascular Systems, Inc. | Vulnerable plaque treatment |
EP1827555A4 (en) | 2004-11-18 | 2010-03-10 | David W Chang | Endoluminal delivery of anesthesia |
US7837650B1 (en) | 2004-12-30 | 2010-11-23 | Advanced Cardiovascular Systems, Inc. | Method and apparatus to prevent reperfusion injury |
US20060161241A1 (en) * | 2005-01-14 | 2006-07-20 | Denise Barbut | Methods and devices for treating aortic atheroma |
US8828433B2 (en) * | 2005-04-19 | 2014-09-09 | Advanced Cardiovascular Systems, Inc. | Hydrogel bioscaffoldings and biomedical device coatings |
US9539410B2 (en) | 2005-04-19 | 2017-01-10 | Abbott Cardiovascular Systems Inc. | Methods and compositions for treating post-cardial infarction damage |
US20080125745A1 (en) | 2005-04-19 | 2008-05-29 | Shubhayu Basu | Methods and compositions for treating post-cardial infarction damage |
US7252834B2 (en) * | 2005-04-25 | 2007-08-07 | Clemson University Research Foundation (Curf) | Elastin stabilization of connective tissue |
WO2007070682A2 (en) * | 2005-12-15 | 2007-06-21 | Massachusetts Institute Of Technology | System for screening particles |
WO2007106554A2 (en) * | 2006-03-14 | 2007-09-20 | Progen Pharmaceuticals, Inc. | Treatment and prevention of vascular hyperplasia using polyamine and polyamine analog compounds |
WO2008105773A2 (en) | 2006-03-31 | 2008-09-04 | Massachusetts Institute Of Technology | System for targeted delivery of therapeutic agents |
CA2652280C (en) | 2006-05-15 | 2014-01-28 | Massachusetts Institute Of Technology | Polymers for functional particles |
WO2007150030A2 (en) | 2006-06-23 | 2007-12-27 | Massachusetts Institute Of Technology | Microfluidic synthesis of organic nanoparticles |
US9533127B2 (en) * | 2006-07-24 | 2017-01-03 | Abbott Cardiovascular Systems Inc. | Methods for inhibiting reperfusion injury |
US7732190B2 (en) * | 2006-07-31 | 2010-06-08 | Advanced Cardiovascular Systems, Inc. | Modified two-component gelation systems, methods of use and methods of manufacture |
US9242005B1 (en) * | 2006-08-21 | 2016-01-26 | Abbott Cardiovascular Systems Inc. | Pro-healing agent formulation compositions, methods and treatments |
US20080085293A1 (en) * | 2006-08-22 | 2008-04-10 | Jenchen Yang | Drug eluting stent and therapeutic methods using c-Jun N-terminal kinase inhibitor |
US7557167B2 (en) * | 2006-09-28 | 2009-07-07 | Gore Enterprise Holdings, Inc. | Polyester compositions, methods of manufacturing said compositions, and articles made therefrom |
US9005672B2 (en) * | 2006-11-17 | 2015-04-14 | Abbott Cardiovascular Systems Inc. | Methods of modifying myocardial infarction expansion |
US8741326B2 (en) | 2006-11-17 | 2014-06-03 | Abbott Cardiovascular Systems Inc. | Modified two-component gelation systems, methods of use and methods of manufacture |
US9737640B2 (en) | 2006-11-20 | 2017-08-22 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414525B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414910B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US20100303723A1 (en) * | 2006-11-20 | 2010-12-02 | Massachusetts Institute Of Technology | Drug delivery systems using fc fragments |
US9700704B2 (en) | 2006-11-20 | 2017-07-11 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US8998846B2 (en) | 2006-11-20 | 2015-04-07 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US8425459B2 (en) | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
US8414909B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414526B2 (en) * | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids |
US20080276935A1 (en) | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
US8192760B2 (en) | 2006-12-04 | 2012-06-05 | Abbott Cardiovascular Systems Inc. | Methods and compositions for treating tissue using silk proteins |
US8114466B2 (en) * | 2007-01-03 | 2012-02-14 | Boston Scientific Scimed, Inc. | Methods of applying coating to the inside surface of a stent |
WO2008098165A2 (en) * | 2007-02-09 | 2008-08-14 | Massachusetts Institute Of Technology | Oscillating cell culture bioreactor |
US20080234657A1 (en) * | 2007-03-22 | 2008-09-25 | Medtronic Vascular, Inc. | Methods for contributing to cardiovascular treatments |
WO2008124634A1 (en) | 2007-04-04 | 2008-10-16 | Massachusetts Institute Of Technology | Polymer-encapsulated reverse micelles |
EP2144600A4 (en) | 2007-04-04 | 2011-03-16 | Massachusetts Inst Technology | Poly (amino acid) targeting moieties |
US20090018633A1 (en) * | 2007-07-10 | 2009-01-15 | Boston Scientific Scimed, Inc. | Protector for an insertable or implantable medical device |
US8858490B2 (en) | 2007-07-18 | 2014-10-14 | Silk Road Medical, Inc. | Systems and methods for treating a carotid artery |
ES2627233T3 (en) | 2007-10-12 | 2017-07-27 | Massachusetts Institute Of Technology | Vaccine Nanotechnology |
US20090148491A1 (en) * | 2007-12-05 | 2009-06-11 | Abbott Cardiovascular Systems Inc. | Dual-Targeted Drug Carriers |
EP2251050A4 (en) * | 2008-03-12 | 2013-08-14 | Anges Mg Inc | Drug elution-type catheter and method for manufacturing the drug elution-type catheter |
US8016842B2 (en) * | 2008-03-25 | 2011-09-13 | Medtronic Vascular, Inc. | Methods for treating vulnerable plaque |
US20090259174A1 (en) * | 2008-04-15 | 2009-10-15 | Medtronic Vascular, Inc. | Methods and devices for treating vulnerable atherosclerotic plaque |
WO2010024898A2 (en) | 2008-08-29 | 2010-03-04 | Lutonix, Inc. | Methods and apparatuses for coating balloon catheters |
US8343498B2 (en) * | 2008-10-12 | 2013-01-01 | Massachusetts Institute Of Technology | Adjuvant incorporation in immunonanotherapeutics |
US8343497B2 (en) | 2008-10-12 | 2013-01-01 | The Brigham And Women's Hospital, Inc. | Targeting of antigen presenting cells with immunonanotherapeutics |
US8591905B2 (en) | 2008-10-12 | 2013-11-26 | The Brigham And Women's Hospital, Inc. | Nicotine immunonanotherapeutics |
US8277812B2 (en) | 2008-10-12 | 2012-10-02 | Massachusetts Institute Of Technology | Immunonanotherapeutics that provide IgG humoral response without T-cell antigen |
DE102008053635A1 (en) * | 2008-10-29 | 2010-05-12 | Acandis Gmbh & Co. Kg | Medical device for recanalization of thrombi |
US8177802B2 (en) * | 2008-12-16 | 2012-05-15 | Medtronic Vascular, Inc. | Apparatus for percutaneously creating native tissue venous valves |
US7955346B2 (en) * | 2008-12-16 | 2011-06-07 | Medtronic Vascular, Inc. | Percutaneous methods for creating native tissue venous valves |
EA201101530A1 (en) * | 2009-04-21 | 2012-03-30 | Селекта Байосайенсиз, Инк. | IMMUNONANOTHERAPY, PROVIDING TH1-DISPERSED RESPONSE |
AU2010254551B2 (en) * | 2009-05-27 | 2016-10-20 | Selecta Biosciences, Inc. | Immunomodulatory agent-polymeric compounds |
US20100331819A1 (en) * | 2009-06-24 | 2010-12-30 | Abbott Cardiovascular Systems Inc. | Drug Delivery System and Method of Treatment of Vascular Diseases Using Photodynamic Therapy |
WO2011044455A1 (en) * | 2009-10-09 | 2011-04-14 | Vatrix Medical, Inc. | In vivo chemical stabilization of vulnerable plaque |
WO2011106735A1 (en) | 2010-02-26 | 2011-09-01 | The Board Of Trustees Of The Leland Stanford Junior University | Systems and methods for endoluminal valve creation |
US8377083B2 (en) * | 2010-04-27 | 2013-02-19 | Medtronic Vascular, Inc. | Percutaneous methods and apparatus for creating native tissue venous valves |
US8460323B2 (en) | 2010-04-27 | 2013-06-11 | Medtronic Vascular, Inc. | Percutaneous methods for apparatus for creating native tissue venous valves |
NO2575876T3 (en) | 2010-05-26 | 2018-05-05 | ||
US8911468B2 (en) | 2011-01-31 | 2014-12-16 | Vatrix Medical, Inc. | Devices, therapeutic compositions and corresponding percutaneous treatment methods for aortic dissection |
EP3388005B1 (en) * | 2011-04-20 | 2020-08-19 | The Board of Trustees of the Leland Stanford Junior University | Systems for endoluminal valve creation |
JP2014516695A (en) | 2011-05-18 | 2014-07-17 | バトリックス・メディカル・インコーポレイテッド | Coated balloon for vascular stabilization |
CA2843274A1 (en) | 2011-07-29 | 2013-02-07 | Selecta Biosciences, Inc. | Synthetic nanocarriers that generate humoral and cytotoxic t lymphocyte (ctl) immune responses |
US10292807B2 (en) | 2012-02-07 | 2019-05-21 | Intervene, Inc. | Systems and methods for endoluminal valve creation |
US9955990B2 (en) | 2013-01-10 | 2018-05-01 | Intervene, Inc. | Systems and methods for endoluminal valve creation |
US11273287B2 (en) | 2013-03-08 | 2022-03-15 | Endobar Solutions Llc | Selectively delivering particles into the distal portion of the left gastric artery |
US20140277059A1 (en) * | 2013-03-12 | 2014-09-18 | Acclarent, Inc. | Apparatus for puncturing balloon in airway dilation shaft |
US9108030B2 (en) | 2013-03-14 | 2015-08-18 | Covidien Lp | Fluid delivery catheter with pressure-actuating needle deployment and retraction |
WO2015048565A2 (en) | 2013-09-27 | 2015-04-02 | Intervene, Inc. | Visualization devices, systems, and methods for informing intravascular procedures on blood vessel valves |
US10188419B2 (en) | 2014-03-24 | 2019-01-29 | Intervene, Inc. | Visualization devices for use during percutaneous tissue dissection and associated systems and methods |
US10098650B2 (en) * | 2014-06-09 | 2018-10-16 | Boston Scientific Scimed, Inc. | Systems and methods for treating atherosclerotic plaque |
WO2016100574A2 (en) | 2014-12-16 | 2016-06-23 | Intervene, Inc. | Intravascular devices, systems, and methods for the controlled dissection of body lumens |
US10646247B2 (en) | 2016-04-01 | 2020-05-12 | Intervene, Inc. | Intraluminal tissue modifying systems and associated devices and methods |
AU2017331242B2 (en) | 2016-09-22 | 2022-07-07 | Mercator Medsystems, Inc. | Treatment of Restenosis using Temsirolimus |
KR20200008166A (en) | 2017-05-26 | 2020-01-23 | 머케이터 메드시스템즈, 인크. | Combination therapy for the treatment of restenosis |
WO2019178231A1 (en) | 2018-03-14 | 2019-09-19 | Mercator Medsystems, Inc. | Medical instrument and medical method for localized drug delivery |
Citations (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4512338A (en) * | 1983-01-25 | 1985-04-23 | Balko Alexander B | Process for restoring patency to body vessels |
US4795459A (en) * | 1987-05-18 | 1989-01-03 | Rhode Island Hospital | Implantable prosthetic device with lectin linked endothelial cells |
US5147377A (en) * | 1988-11-23 | 1992-09-15 | Harvinder Sahota | Balloon catheters |
US5246451A (en) * | 1991-04-30 | 1993-09-21 | Medtronic, Inc. | Vascular prosthesis and method |
US5282785A (en) * | 1990-06-15 | 1994-02-01 | Cortrak Medical, Inc. | Drug delivery apparatus and method |
US5545208A (en) * | 1990-02-28 | 1996-08-13 | Medtronic, Inc. | Intralumenal drug eluting prosthesis |
US5674241A (en) * | 1995-02-22 | 1997-10-07 | Menlo Care, Inc. | Covered expanding mesh stent |
US5700286A (en) * | 1994-12-13 | 1997-12-23 | Advanced Cardiovascular Systems, Inc. | Polymer film for wrapping a stent structure |
US5707358A (en) * | 1996-05-13 | 1998-01-13 | Wright; John T. M. | Dual concentric balloon catheter for retrograde cardioplegia perfusion |
US5776184A (en) * | 1993-04-26 | 1998-07-07 | Medtronic, Inc. | Intravasoular stent and method |
US5935075A (en) * | 1995-09-20 | 1999-08-10 | Texas Heart Institute | Detecting thermal discrepancies in vessel walls |
US5957974A (en) * | 1997-01-23 | 1999-09-28 | Schneider (Usa) Inc | Stent graft with braided polymeric sleeve |
US6029671A (en) * | 1991-07-16 | 2000-02-29 | Heartport, Inc. | System and methods for performing endovascular procedures |
US6100443A (en) * | 1989-06-12 | 2000-08-08 | Oklahoma Medical Research Foundation | Universal donor cells |
US6117166A (en) * | 1997-10-27 | 2000-09-12 | Winston; Thomas R. | Apparatus and methods for grafting blood vessel tissue |
US6156727A (en) * | 1996-09-05 | 2000-12-05 | Uab Research Foundation | Anti-atherosclerotic peptides and a transgenic mouse model of antherosclerosis |
US6248129B1 (en) * | 1990-09-14 | 2001-06-19 | Quanam Medical Corporation | Expandable polymeric stent with memory and delivery apparatus and method |
US20020026145A1 (en) * | 1997-03-06 | 2002-02-28 | Bagaoisan Celso J. | Method and apparatus for emboli containment |
US20020062147A1 (en) * | 2000-03-13 | 2002-05-23 | Jun Yang | Stent having cover with drug delivery capability |
US20020077592A1 (en) * | 1994-06-30 | 2002-06-20 | Boston Scientific Corporation | Replenishable stent and delivery system |
US6419659B1 (en) * | 2000-02-10 | 2002-07-16 | Medventure Technology Corp | Lipid pool aspiration arrangement for the treatment of vulnerable atherosclerosis plaque |
US6451044B1 (en) * | 1996-09-20 | 2002-09-17 | Board Of Regents, The University Of Texas System | Method and apparatus for heating inflammed tissue |
US6454796B1 (en) * | 2000-05-05 | 2002-09-24 | Endovascular Technologies, Inc. | Vascular graft |
US6494862B1 (en) * | 1999-07-13 | 2002-12-17 | Advanced Cardiovascular Systems, Inc. | Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway |
US20030060877A1 (en) * | 2001-09-25 | 2003-03-27 | Robert Falotico | Coated medical devices for the treatment of vascular disease |
US6540734B1 (en) * | 2000-02-16 | 2003-04-01 | Advanced Cardiovascular Systems, Inc. | Multi-lumen extrusion tubing |
US20030065377A1 (en) * | 2001-09-28 | 2003-04-03 | Davila Luis A. | Coated medical devices |
US6547767B1 (en) * | 2000-11-14 | 2003-04-15 | Advanced Cardiovascular Systems, Inc. | Syringe assembly for a catheter |
US20030103995A1 (en) * | 2001-06-04 | 2003-06-05 | Hamblin Michael R. | Detection and therapy of vulnerable plaque with photodynamic compounds |
US6575932B1 (en) * | 1999-12-02 | 2003-06-10 | Ottawa Heart Institute | Adjustable multi-balloon local delivery device |
US20030120297A1 (en) * | 2001-12-20 | 2003-06-26 | Beyerlein Dagmar Bettina | Contact and penetration depth sensor for a needle assembly |
US6660034B1 (en) * | 2001-04-30 | 2003-12-09 | Advanced Cardiovascular Systems, Inc. | Stent for increasing blood flow to ischemic tissues and a method of using the same |
US20030230313A1 (en) * | 2002-03-13 | 2003-12-18 | Ehsan Alipour | Imaging of the vasa vasorum to navigate through an occlusion |
US6669652B2 (en) * | 2000-12-21 | 2003-12-30 | Advanced Cardiovascular Systems, Inc. | Guidewire with tapered distal coil |
US20040002755A1 (en) * | 2002-06-28 | 2004-01-01 | Fischell David R. | Method and apparatus for treating vulnerable coronary plaques using drug-eluting stents |
US20040010309A1 (en) * | 2002-06-28 | 2004-01-15 | Endobionics, Inc. | Methods and systems for delivering liquid substances to tissues surrounding body lumens |
US6709427B1 (en) * | 1999-08-05 | 2004-03-23 | Kensey Nash Corporation | Systems and methods for delivering agents into targeted tissue of a living being |
US20040064093A1 (en) * | 2002-08-21 | 2004-04-01 | Hektner Thomas R. | Vascular treatment method and device |
US6719750B2 (en) * | 2000-08-30 | 2004-04-13 | The Johns Hopkins University | Devices for intraocular drug delivery |
US6755856B2 (en) * | 1998-09-05 | 2004-06-29 | Abbott Laboratories Vascular Enterprises Limited | Methods and apparatus for stenting comprising enhanced embolic protection, coupled with improved protection against restenosis and thrombus formation |
US20040127475A1 (en) * | 1999-12-29 | 2004-07-01 | Estrogen Vascular Technology, Llc | Apparatus and method for delivering compounds to a living organism |
US6761696B1 (en) * | 2001-11-13 | 2004-07-13 | Advanced Cardiovascular Systems, Inc. | Guide wire with a non-rectangular shaping member |
US20040138642A1 (en) * | 2003-01-10 | 2004-07-15 | Fischer Dan E. | Fiber-coated dental infusor systems and methods of use |
US20040143322A1 (en) * | 2002-11-08 | 2004-07-22 | Conor Medsystems, Inc. | Method and apparatus for treating vulnerable artherosclerotic plaque |
US20040181206A1 (en) * | 2003-03-12 | 2004-09-16 | Chiu Jessica G. | Retrograde pressure regulated infusion |
US20040220660A1 (en) * | 2001-02-05 | 2004-11-04 | Shanley John F. | Bioresorbable stent with beneficial agent reservoirs |
US20040260239A1 (en) * | 1996-10-10 | 2004-12-23 | Kusleika Richard S. | Catheter for tissue dilation and drug delivery |
US20040267354A1 (en) * | 1994-05-13 | 2004-12-30 | Ringeisen Timothy A. | Method for making a porous polymeric material |
US20050004663A1 (en) * | 2001-05-07 | 2005-01-06 | Llanos Gerard H. | Heparin barrier coating for controlled drug release |
US6866650B2 (en) * | 1991-07-16 | 2005-03-15 | Heartport, Inc. | System for cardiac procedures |
US20050070844A1 (en) * | 2003-09-30 | 2005-03-31 | Mina Chow | Deflectable catheter assembly and method of making same |
US20050251246A1 (en) * | 1998-04-27 | 2005-11-10 | Artemis Medical, Inc. | Dilating and support apparatus with disease inhibitors and methods for use |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5464395A (en) * | 1994-04-05 | 1995-11-07 | Faxon; David P. | Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway |
US7744584B2 (en) | 2002-01-22 | 2010-06-29 | Mercator Medsystems, Inc. | Methods and kits for volumetric distribution of pharmaceutical agents via the vascular adventitia and microcirculation |
-
2002
- 2002-09-30 US US10/262,151 patent/US7008411B1/en not_active Expired - Lifetime
-
2005
- 2005-11-17 US US11/283,032 patent/US20060135943A1/en not_active Abandoned
Patent Citations (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4512338A (en) * | 1983-01-25 | 1985-04-23 | Balko Alexander B | Process for restoring patency to body vessels |
US4795459A (en) * | 1987-05-18 | 1989-01-03 | Rhode Island Hospital | Implantable prosthetic device with lectin linked endothelial cells |
US5147377A (en) * | 1988-11-23 | 1992-09-15 | Harvinder Sahota | Balloon catheters |
US6100443A (en) * | 1989-06-12 | 2000-08-08 | Oklahoma Medical Research Foundation | Universal donor cells |
US5997468A (en) * | 1990-02-28 | 1999-12-07 | Medtronic, Inc. | Intraluminal drug eluting prosthesis method |
US5545208A (en) * | 1990-02-28 | 1996-08-13 | Medtronic, Inc. | Intralumenal drug eluting prosthesis |
US5282785A (en) * | 1990-06-15 | 1994-02-01 | Cortrak Medical, Inc. | Drug delivery apparatus and method |
US6248129B1 (en) * | 1990-09-14 | 2001-06-19 | Quanam Medical Corporation | Expandable polymeric stent with memory and delivery apparatus and method |
US5246451A (en) * | 1991-04-30 | 1993-09-21 | Medtronic, Inc. | Vascular prosthesis and method |
US6866650B2 (en) * | 1991-07-16 | 2005-03-15 | Heartport, Inc. | System for cardiac procedures |
US6029671A (en) * | 1991-07-16 | 2000-02-29 | Heartport, Inc. | System and methods for performing endovascular procedures |
US5776184A (en) * | 1993-04-26 | 1998-07-07 | Medtronic, Inc. | Intravasoular stent and method |
US20040267354A1 (en) * | 1994-05-13 | 2004-12-30 | Ringeisen Timothy A. | Method for making a porous polymeric material |
US20020077592A1 (en) * | 1994-06-30 | 2002-06-20 | Boston Scientific Corporation | Replenishable stent and delivery system |
US5700286A (en) * | 1994-12-13 | 1997-12-23 | Advanced Cardiovascular Systems, Inc. | Polymer film for wrapping a stent structure |
US5674241A (en) * | 1995-02-22 | 1997-10-07 | Menlo Care, Inc. | Covered expanding mesh stent |
US5935075A (en) * | 1995-09-20 | 1999-08-10 | Texas Heart Institute | Detecting thermal discrepancies in vessel walls |
US5707358A (en) * | 1996-05-13 | 1998-01-13 | Wright; John T. M. | Dual concentric balloon catheter for retrograde cardioplegia perfusion |
US6156727A (en) * | 1996-09-05 | 2000-12-05 | Uab Research Foundation | Anti-atherosclerotic peptides and a transgenic mouse model of antherosclerosis |
US6451044B1 (en) * | 1996-09-20 | 2002-09-17 | Board Of Regents, The University Of Texas System | Method and apparatus for heating inflammed tissue |
US20040260239A1 (en) * | 1996-10-10 | 2004-12-23 | Kusleika Richard S. | Catheter for tissue dilation and drug delivery |
US5957974A (en) * | 1997-01-23 | 1999-09-28 | Schneider (Usa) Inc | Stent graft with braided polymeric sleeve |
US20020026145A1 (en) * | 1997-03-06 | 2002-02-28 | Bagaoisan Celso J. | Method and apparatus for emboli containment |
US6117166A (en) * | 1997-10-27 | 2000-09-12 | Winston; Thomas R. | Apparatus and methods for grafting blood vessel tissue |
US20050251246A1 (en) * | 1998-04-27 | 2005-11-10 | Artemis Medical, Inc. | Dilating and support apparatus with disease inhibitors and methods for use |
US6755856B2 (en) * | 1998-09-05 | 2004-06-29 | Abbott Laboratories Vascular Enterprises Limited | Methods and apparatus for stenting comprising enhanced embolic protection, coupled with improved protection against restenosis and thrombus formation |
US20020193785A1 (en) * | 1998-12-31 | 2002-12-19 | Morteza Naghavi | Method and apparatus for heating inflammed tissue |
US20030040712A1 (en) * | 1999-07-13 | 2003-02-27 | Pinaki Ray | Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway |
US6494862B1 (en) * | 1999-07-13 | 2002-12-17 | Advanced Cardiovascular Systems, Inc. | Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway |
US6709427B1 (en) * | 1999-08-05 | 2004-03-23 | Kensey Nash Corporation | Systems and methods for delivering agents into targeted tissue of a living being |
US6575932B1 (en) * | 1999-12-02 | 2003-06-10 | Ottawa Heart Institute | Adjustable multi-balloon local delivery device |
US20040127475A1 (en) * | 1999-12-29 | 2004-07-01 | Estrogen Vascular Technology, Llc | Apparatus and method for delivering compounds to a living organism |
US6419659B1 (en) * | 2000-02-10 | 2002-07-16 | Medventure Technology Corp | Lipid pool aspiration arrangement for the treatment of vulnerable atherosclerosis plaque |
US6540734B1 (en) * | 2000-02-16 | 2003-04-01 | Advanced Cardiovascular Systems, Inc. | Multi-lumen extrusion tubing |
US20020062147A1 (en) * | 2000-03-13 | 2002-05-23 | Jun Yang | Stent having cover with drug delivery capability |
US6454796B1 (en) * | 2000-05-05 | 2002-09-24 | Endovascular Technologies, Inc. | Vascular graft |
US6719750B2 (en) * | 2000-08-30 | 2004-04-13 | The Johns Hopkins University | Devices for intraocular drug delivery |
US6547767B1 (en) * | 2000-11-14 | 2003-04-15 | Advanced Cardiovascular Systems, Inc. | Syringe assembly for a catheter |
US6669652B2 (en) * | 2000-12-21 | 2003-12-30 | Advanced Cardiovascular Systems, Inc. | Guidewire with tapered distal coil |
US20040220660A1 (en) * | 2001-02-05 | 2004-11-04 | Shanley John F. | Bioresorbable stent with beneficial agent reservoirs |
US6660034B1 (en) * | 2001-04-30 | 2003-12-09 | Advanced Cardiovascular Systems, Inc. | Stent for increasing blood flow to ischemic tissues and a method of using the same |
US20050004663A1 (en) * | 2001-05-07 | 2005-01-06 | Llanos Gerard H. | Heparin barrier coating for controlled drug release |
US20030103995A1 (en) * | 2001-06-04 | 2003-06-05 | Hamblin Michael R. | Detection and therapy of vulnerable plaque with photodynamic compounds |
US20030060877A1 (en) * | 2001-09-25 | 2003-03-27 | Robert Falotico | Coated medical devices for the treatment of vascular disease |
US20030065377A1 (en) * | 2001-09-28 | 2003-04-03 | Davila Luis A. | Coated medical devices |
US6761696B1 (en) * | 2001-11-13 | 2004-07-13 | Advanced Cardiovascular Systems, Inc. | Guide wire with a non-rectangular shaping member |
US20030120297A1 (en) * | 2001-12-20 | 2003-06-26 | Beyerlein Dagmar Bettina | Contact and penetration depth sensor for a needle assembly |
US20030230313A1 (en) * | 2002-03-13 | 2003-12-18 | Ehsan Alipour | Imaging of the vasa vasorum to navigate through an occlusion |
US20040010309A1 (en) * | 2002-06-28 | 2004-01-15 | Endobionics, Inc. | Methods and systems for delivering liquid substances to tissues surrounding body lumens |
US20040002755A1 (en) * | 2002-06-28 | 2004-01-01 | Fischell David R. | Method and apparatus for treating vulnerable coronary plaques using drug-eluting stents |
US20040064093A1 (en) * | 2002-08-21 | 2004-04-01 | Hektner Thomas R. | Vascular treatment method and device |
US20040143322A1 (en) * | 2002-11-08 | 2004-07-22 | Conor Medsystems, Inc. | Method and apparatus for treating vulnerable artherosclerotic plaque |
US20040138642A1 (en) * | 2003-01-10 | 2004-07-15 | Fischer Dan E. | Fiber-coated dental infusor systems and methods of use |
US20040181206A1 (en) * | 2003-03-12 | 2004-09-16 | Chiu Jessica G. | Retrograde pressure regulated infusion |
US20050070844A1 (en) * | 2003-09-30 | 2005-03-31 | Mina Chow | Deflectable catheter assembly and method of making same |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7862605B2 (en) | 1995-06-07 | 2011-01-04 | Med Institute, Inc. | Coated implantable medical device |
WO2010065026A3 (en) * | 2007-10-03 | 2010-08-19 | The General Hospital Corporation | Photochemical tissue bonding |
US20090306120A1 (en) * | 2007-10-23 | 2009-12-10 | Florencia Lim | Terpolymers containing lactide and glycolide |
US20090118700A1 (en) * | 2007-11-07 | 2009-05-07 | Callas Peter L | Method for treating coronary vessels |
US9504491B2 (en) * | 2007-11-07 | 2016-11-29 | Abbott Cardiovascular Systems Inc. | Catheter having window and partial balloon covering for dissecting tissue planes and injecting treatment agent to coronary blood vessel |
US20090254051A1 (en) * | 2007-12-06 | 2009-10-08 | Abbott Laboratories | Device and method for treating vulnerable plaque |
US20090291111A1 (en) * | 2008-05-21 | 2009-11-26 | Florencia Lim | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
US8661630B2 (en) | 2008-05-21 | 2014-03-04 | Abbott Cardiovascular Systems Inc. | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
US9592323B2 (en) | 2008-05-21 | 2017-03-14 | Abbott Cardiovascular Systems Inc. | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
CN106725249A (en) * | 2017-01-04 | 2017-05-31 | 许娟 | Accurate medicine equipment |
US9848906B1 (en) | 2017-06-20 | 2017-12-26 | Joe Michael Eskridge | Stent retriever having an expandable fragment guard |
US11266435B2 (en) | 2017-06-20 | 2022-03-08 | Joe Michael Eskridge | Stent retriever having an expandable fragment guard |
Also Published As
Publication number | Publication date |
---|---|
US7008411B1 (en) | 2006-03-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7008411B1 (en) | Method and apparatus for treating vulnerable plaque | |
US8652194B1 (en) | Method and apparatus for treating vulnerable plaque | |
US20060265043A1 (en) | Method and apparatus for treating vulnerable plaque | |
CN104013996B (en) | The drug eluting implantable medical device of progenitor endothelial cell capturing | |
JP6889193B2 (en) | Compounds and methods for the prevention or treatment of restenosis | |
US20110313502A1 (en) | Composite vascular prosthesis | |
EP1847235A1 (en) | Devices for contributing to improved stent graft fixation | |
PT1699503E (en) | Devices coated with pec polymers | |
JP2008517662A (en) | Biocompatible and blood compatible polymer compositions | |
US10925863B2 (en) | Combination therapy for treatment of restenosis | |
CN103974676A (en) | Subintimal recanalization with bio-absorbable stent | |
AU2412700A (en) | Composition and methods for administration of water-insoluble paclitaxel derivatives | |
CA2820405C (en) | Removable stent and method of production | |
JP2013236940A (en) | In-vivo indwelling matter | |
WO2007075388A2 (en) | Methods of locally treating and preventing cardiac disorders | |
JP2021511891A (en) | Methods and devices for reducing vascular smooth muscle cell proliferation | |
CN112263360A (en) | In vivo drug eluting stent and preparation method thereof | |
Boeder et al. | First-in-Man Lithoplasty of a LIMA Bypass With ECMO Support in a Last-Remaining Vessel | |
US20050267564A1 (en) | Capsulated stent and its uses | |
JP2009077963A (en) | In vivo indwelling object | |
Talekar | STUDIES ON DRUG ELUTING STENTS IN PREVENTION OF RENAL ARTERY STENOSIS IN DOGS | |
KR20160122949A (en) | Drug releasing stent and manufacturing method of the same | |
JP2010166935A (en) | Stent | |
JP2004041331A (en) | Intracorporeal embedded medical appliance |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |