AU2002239436A1 - Coated implantable medical device - Google Patents
Coated implantable medical deviceInfo
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Description
COATED IMPLANTABLE MEDICAL DEVICE
Description Technical Field
This invention relates generally to human and veterinary medical devices and, more particularly, to devices incorporating drugs, bioactive agents, therapeutic agents or diagnostic agents. Background of the Invention
It has become common to treat a variety of medical conditions by temporarily or permanently introducing an implantable medical device partly or completely into the esophagus, trachea, colon, biliary tract, urinary tract, vascular system or other location within a human or veterinary patient. Many treatments of the vascular or other systems entail the introduction of a device such as a stent, a catheter, a balloon, a wire guide, a cannula or the like. For this purpose, a stent may most simply be considered as a cylinder of relatively short length which opens a body passage or lumen or which maintains a body passage or lumen in an open condition.
Such medical devices are generally capable of serving their intended purposes quite well. Some drawbacks can be encountered during their use, however. For example, when a device is introduced into and manipulated through the vascular system of a patient, the blood vessel walls can be disturbed or injured. Clot formation or thrombosis often results at the injured site, causing stenosis (closure) of the blood vessel. Moreover, if the medical device is left within the patient for an extended period of time, thrombus often forms on the device itself, again causing stenosis. As a result, the patient is placed at risk of a variety of complications, including heart attack, pulmonary embolism, and stroke. Thus, the use of such a medical device can entail the risk of precisely the problems that its use was intended to ameliorate.
Another way in which blood vessels undergo stenosis is through disease. Probably the most common disease causing stenosis of blood vessels is atherosclerosis. Many medical devices and therapeutic methods are known for the treatment of atherosclerotic disease. One particularly useful therapy for certain
atherosclerotic lesions is percutaneous transluminal angioplasty (PTA). During PTA, a balloon-tipped catheter is inserted in a patient's artery, the balloon being deflated. The tip of the catheter is advanced to the site of the atherosclerotic plaque to be dilated. The balloon is placed within or across the stenotic segment of the artery, and then inflated. Inflation of the balloon "cracks" the atherosclerotic plaque and expands the vessel, thereby relieving the stenosis, at least in part.
While PTA presently enjoys wide use, it suffers from two major problems. First, the blood vessel may suffer acute occlusion immediately after or within the initial hours after the dilation procedure. Such occlusion is referred to as "abrupt closure." Abrupt closure occurs in perhaps five percent or so of the cases in which PTA is employed, and can result in myocardial infarction and death if blood flow is not restored promptly. The primary mechanisms of abrupt closures are believed to be elastic recoil, arterial dissection and/or thrombosis. It has been postulated that the delivery of an appropriate agent (such as an antithrombic) directly into the arterial wall at the time of angioplasty could reduce the incidence of thrombotic acute closure, but the results of attempts to do so have been mixed.
A second major problem encountered in PTA is the re-narrowing of an artery after an initially successful angioplasty. This re-narrowing is referred to as "restenosis" and typically occurs within the first six months after angioplasty. Restenosis is believed to arise through the proliferation and migration of cellular components from the arterial wall, as well as through geometric changes in the arterial wall referred to as "remodeling." It has similarly been postulated that the delivery of appropriate agents directly into the arterial wall could interrupt the cellular and/or remodeling events leading to restenosis. However, like the attempts to prevent thrombotic acute closure, the results of attempts to prevent restenosis in this manner have been mixed.
Non-atherosclerotic vascular stenosis may also be treated by PTA. For example, Takayasu arteritis or neurofibromatosis may cause stenosis by fibrotic thickening of the arterial wall. Restenosis of these lesions occurs at a high rate following angioplasty, however, due to the fibrotic nature of the diseases. Medical therapies to treat or obviate them have been similarly disappointing.
A device such as an intravascular stent can be a useful adjunct to PTA, particularly in the case of either acute or threatened closure after angioplasty. The stent is placed in the dilated segment of the artery to mechanically prevent abrupt closure and restenosis. Unfortunately, even when the implantation of the stent is accompanied by aggressive and precise antiplatelet and anticoagulation therapy (typically by systemic administration), the incidence of thrombotic vessel closure or other thrombotic complication remains significant, and the prevention of restenosis is not as successful as desired. Furthermore, an undesirable side effect of the systemic antiplatelet and anticoagulation therapy is an increased incidence of bleeding complications, most often at the percutaneous entry site.
Other conditions and diseases are treatable with stents, catheters, cannulae and other medical devices inserted into the esophagus, trachea, colon, biliary tract, urinary tract and other locations in the body. A wide variety of bioactive materials (drugs, therapeutic agents, diagnostic agents and other materials having biological or pharmacological activity within a patient) have been applied to such medical devices for the purpose of introducing such materials into the patient. Unfortunately, the durable application of bioactive materials to stents and the like, sufficient for such introduction to successfully occur, is often problematic. A range of containment or layering materials have been applied to such devices to permit the timed release of bioactive materials from such devices, or even to permit bioactive materials to be applied to such devices at all. Unfortunately, the use of such containment materials can significantly increase the time and cost of manufacturing suitable implantable devices. Moreover, some bioactive materials may not be able to withstand incorporation in known containment materials. Additionally, certain containment materials may not be biocompatible and may cause problems of the type desired to be reduced.
It would be desirable to develop devices and methods for reliably delivering suitable therapeutic and diagnostic agents, drugs and other bioactive materials directly into a body portion during or following a medical procedure, so as to treat or prevent the conditions and diseases mentioned above, for example, to prevent abrupt closure and/or restenosis of a body portion such as a passage, lumen or blood vessel.
It would also be desirable to limit systemic exposure of the patient to such bioactive materials. This would be particularly advantageous in therapies involving the delivery of a chemotherapeutic agent to a particular organ or site through an intravenous catheter (which itself has the advantage of reducing the amount of agent needed for successful treatment), by preventing stenosis both along the catheter and at the catheter tip. It would be desirable to similarly improve other therapies. Of course, it would also be desirable to avoid degradation of the agent, drug or bioactive material during its incorporation on or into any such device. It would further be highly desirable to develop a method for coating an implantable medical device with a drug, therapeutic agent, diagnostic agent or other bioactive material which entailed a minimum number of steps, thereby reducing the ultimate cost of treating the patient. It would be desirable to deliver the bioactive material without causing additional problems with a poor biocompatible carrier or containment material. Finally, it would be highly desirable to develop a method for coating an implantable medical device with a drug, therapeutic agent, diagnostic agent or other bioactive material which could be carried out in such a way as to minimize any environmental or personal risks or inconveniences associated with the manufacture of the device. Summary of the Invention
The foregoing problems are solved and a technical advance is achieved in an illustrative embodiment of a medical device of the present invention coated (at least in part) with a drug, therapeutic agent, diagnostic agent or other bioactive or pharmacologically active material. (Hereinafter, any or all of these will be collectively referred to as "a bioactive material" or "bioactive materials."). The specific improvement of the present invention entails attaining a desired surface roughness, or texturing, on the surface of the device by whatever treatment of the surface and applying the bioactive material directly to that roughened or textured surface without the need of any further overlying or containment layer or coating. Unexpectedly, this straightforward expedient yields a coated implantable medical device which is sufficiently durable to withstand the desired implantation without suffering an unacceptable amount of loss (if any) of bioactive material from the device. In one aspect of the invention, at least a part of the surface of the device, for example the
outer surface of a stent, is treated to produce a roughened, uneven, or unsmooth surface, and the bioactive material is formed or posited on at least the part of the surface. The degree of surface treatment is controlled to provide sufficient adhesion of the bioactive material to the device surface.
In the preferred embodiment of the medical device of the present invention, the device first comprises a structure adapted for temporary or permanent introduction into the esophagus, trachea, colon, biliary tract, urinary tract, vascular system or other location in a human or veterinary patient. The structure comprises a base material (preferably non-porous) having a roughened or textured surface. The surface of the base material can be roughened or textured by etching but is preferably roughened or textured by abrasion with an abrasive grit, most preferably sodium bicarbonate (USP) .
The medical device of the present invention also comprises a layer of bioactive material posited directly upon the roughened or textured surface of the base material of the structure. Furthermore, the device advantageously does not require or is free of any additional coating or layer atop the layer of bioactive material.
As described in more detail below, the base material of the structure and the bioactive material posited on that base material can comprise any of a wide range of suitable materials. The selection of a specific combination of base material, bioactive material and surface roughness or texture depends upon the intended use of the medical device. Although texture may have a meaning of a repeatable pattern, this is clearly not the intent. The surface of the stent is that of any topography, whether repeatable or not, that helps improve adhesion of the bioactive material on the base material or modification thereof. Hereinafter, a textured surface will include a roughened, uneven, or unsmooth surface. The suitability of a chosen combination can readily be determined by an adhesion test which simulates the actual delivery of bioactive material during introduction and deployment of the device in a patient. Such a test is straightforward and is believed not to entail an undue amount of experimentation, particularly in comparison to the amount and technical level of testing required before a product of this type can be marketed in the United States.
The medical device of the present invention and its method of manufacture
have several advantages over prior stents and other medical devices and methods for manufacturing them. The time and cost of manufacture of the medical device are minimized by the absence of any steps to incorporate the bioactive material in a containment layer, or to apply a containment or time-release layer over the bioactive material. The particularly preferred use of sodium bicarbonate as the abrasive to treat, roughen, or texture the surface of the base material of the structure enjoys several indirect cost savings resulting from the low toxicity of the sodium bicarbonate to production workers, the ease of product and waste cleanup, and the biocompatibility of any residual sodium bicarbonate. Worker safety and ease of product and waste cleanup are, of course, important advantages in their own right.
In a first aspect, then, the present invention is directed to a medical device comprising: a structure adapted for introduction into a patient, the structure comprising a base material (preferably non-porous) having a at least one of a roughened, uneven, unsmooth, or textured surface; and a layer of a bioactive material posited directly upon the surface of the base material of the structure. Furthermore, the medical device does not require or is free of any additional coating or layer atop the layer of bioactive material for delivering the bioactive material. The structure is preferably configured as a stent, such as a vascular or other stent.
The base material of the structure preferably comprises at least one of: stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, or another biocompatible metal, or alloys of any of these; carbon or carbon fiber; cellulose acetate, cellulose nitrate, silicone, polyethylene terephthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or another biocompatible polymeric material, or mixtures or copolymers of these; polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate or another biodegradable polymer, or mixtures or copolymers of these; a protein, an extracellular matrix component, collagen, fibrin or another biologic agent; or a suitable mixture of any of these.
The bioactive material of the layer on the roughened, uneven, unsmooth,
or textured surface of the base material preferably comprises at least one of: paclitaxel; estrogen or estrogen derivatives; heparin or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L-poly-L-arginyl chloromethyl ketone or another antithrombogenic agent, or mixtures thereof; urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof; a fibrinolytic agent; a vasospasm inhibitor; a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator; an antimicrobial agent or antibiotic; aspirin, ticlopdine or another antiplatelet agent; colchicine or another antimitotic, or another microtubule inhibitor; cytochalasin or another actin inhibitor; a remodelling inhibitor; deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention; GP llb/llla, GP Ib-IX or another inhibitor or surface glycoprotein receptor; methotrexate or another antimetabolite or antiproliferative agent; an anti-cancer chemotherapeutic agent; dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid; dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist; 60Co (having a half life of 5.3 years), 192lr (73.8 days), 32P (14.3 days), 111ln (68 hours), 90Y (64 hours), 99mTc (6 hours) or another radiotherapeutic agent; iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent; a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent; captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor; ascorbic acid, alphatocopherol, superoxide dismutase, deferoxyamine, a 21 - aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant; angiopeptin; a 14C-, 3H-, 131l-, 32P- or 36S-radiolabelled form or other radiolabelled form of any of the foregoing; or a mixture of any of these.
Preferably, the roughened, uneven, unsmooth, or textured surface of the base material of the structure has a mean surface roughness of about 10 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 1 00 //in. (about 25 nm and about 2.5 μm).
In a second aspect, the present invention is directed to a medical device
comprising: a structure adapted for introduction into a patient, the structure comprising a base material having a roughened, uneven, unsmooth, or textured surface, the structure being configured as a vascular stent and the base material comprising at least one of stainless steel, nitinol, or an allow of nickel and titanium; and a layer of a bioactive material posited directly upon the roughened or textured surface of the base material of the structure, the bioactive material comprising paclitaxel; wherein the medical device does not require or is free of any additional coating or layer atop the layer of bioactive material; and wherein the roughened or textured surface of the base material of the structure has a mean surface roughness of about 10 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 100 //in. (about 25 nm and about 2.5 μm).
In a third aspect, the present invention is directed to a method of manufacturing a medical device comprising the steps of: providing a structure adapted for introduction into a patient, the structure comprising a base material (preferably non-porous) having a surface; roughening or texturing the surface of the base material of the structure; and positing a layer of a bioactive material directly upon the roughened or textured surface of the base material of the structure; the method being characterized in that the resulting medical device does not require or is free of any additional coating or layer atop the layer of bioactive material.
Preferably, the method is carried out with a structure configured as a stent, such as a vascular stent. The method is preferably carried out with a base material and a bioactive material as described in the first aspect of the invention above.
The positing step of the method is preferably carried out by spraying a solution of the bioactive material on the roughened or textured surface of the base material of the structure. Dipping the base material in a solution of the bioactive material is also contemplated in the practice of the present invention.
The roughening or texturing step of the method is preferably carried out by abrading the surface of the base material of the structure. Etching of the surface is also contemplated in the practice of the present invention.
Abrading of the surface of the base material is preferably carried out with
an abrasive grit comprising at least one of sodium bicarbonate (USP), calcium carbonate, aluminum oxide, colmanite (calcium borate), crushed glass or crushed walnut shells. More preferably, the abrading is carried out with an abrasive grit having a particle size of about 5 microns (5 μm) to about 500 microns (500 μm) . Even more preferably, the abrading is carried out with sodium bicarbonate (USP) having a nominal particle size of about 50 microns (50 μm) .
Abrading of the surface of the base material is preferably carried out with an abrasive grit delivered at a pressure under flow of about 5 to about 200 PSI (about 34 to about 1 380 KPa) and at a grit feed rate of about 1 to about 1 000 g/min. Abrading of the surface is preferably carried out so as to yield a textured surface on the base material having a mean surface roughness of about 10 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 100 //in. (about 25 nm and about 2.5 μm) .
In another aspect, the present invention is directed to the product of the method described in the third aspect of the invention, above. In yet a further aspect, the present invention is directed to a method of medical treatment or diagnosis which comprises introducing the medical device of the present invention, or the product of the method of the present invention, into a human or veterinary patient.
Again, as indicated above, the medical device of the present invention and its method of manufacture have several advantages over prior stents and other medical devices and methods for manufacturing them. The time and cost of manufacture of the medical device of the present invention are minimized by the absence of any steps to incorporate the bioactive material in a containment layer, or to apply a containment or time-release layer over the bioactive material. The particularly preferred use of sodium bicarbonate as the abrasive to roughen or texture the surface of the base material of the structure enjoys cost savings resulting from the low toxicity of the sodium bicarbonate to production workers, the ease of product and waste cleanup, and the biocompatibility of any residual sodium bicarbonate. It should go without saying that the good worker safety and ease of product and waste cleanup enjoyed by the method of the present invention are highly desirable advantages, without regard to any costs saved.
Brief Description of the Drawing
A better understanding of the present invention will now be had upon reference to the following detailed description, when read in conjunction with the accompanying drawing, wherein like reference characters refer to like parts throughout the several views, and in which:
Fig. 1 is a side view showing one of the steps of the method of the preferred embodiment of the present invention; and
Fig. 2 is an enlarged cross-sectional view of a portion of the medical device and product of the preferred embodiment of the present invention. Detailed Description
With reference now to the Figures, an implantable medical device 1 0 in accordance with the present invention is thereshown. The medical device 10 of the present invention first comprises a structure 1 2 adapted for temporary or permanent introduction into a human or veterinary patient. "Adapted" means that the structure 1 2 is particularly configured, shaped and sized for such introduction. By way of example, the structure 1 2 is most preferably configured as a vascular stent adapted for insertion into the vascular system of the patient.
The structure 1 2 can of course be particularly configured for use in other systems and sites such as the esophagus, trachea, colon, biliary ducts, urethra and ureters, among others. Indeed, the structure 1 2 can alternatively be configured as any conventional vascular or other comparable medical device, and can include any of a variety of conventional stent or other adjuncts, such as helically wound strands, perforated cylinders or the like. Moreover, because the problems addressed by the present invention arise primarily with respect to those portions of the device actually positioned within the patient, the inserted structure 1 2 need not be an entire device, but can merely be that portion of a vascular or other device which is intended to be introduced into the patient. Accordingly, the structure 1 2 can be configured as at least one of, or any portion of, a catheter, a wire guide, a cannula, a stent, a vascular or other graft, a cardiac pacemaker lead or lead tip, a cardiac defibrillator lead or lead tip, a heart valve, a suture, a needle, an angioplasty device or a pacemaker. The structure 1 2 can also be configured as a combination of portions of any of these.
For ease of understanding the present invention, Figs. 1 and 2 show only a structure 1 2 configured as a stent, and more particularly, a vascular stent. More preferably, the structure 1 2 is configured as a vascular stent such as the"LOGIC" stent, the "V-FLEX PLUS" stent, or the "ACHIEVE" stent, all commercially available from Cook Incorporated, Bloomington, Indiana. Such stents are cut from a cannula of suitable material and possess a plurality of interconnected struts allowing the stents to expand upon inflation of a balloon on which they are carried. They possess a flat outer surface, which as a practical matter makes them easier to process via the present invention than stents made of a plurality of round wires; the latter are more difficult to abrade. These stents possess a smooth inside surface to reduce the possibility of thrombogenesis.
The particular shape and dimensions of the structure 1 2 should of course be selected as required for its specific purpose and for the particular site in the patient at which it will be employed, such as in the coronary arteries, aorta, esophagus, trachea, colon, biliary tract or urinary tract. A structure 1 2 intended for each location will have different dimensions particularly suited to such use. For example, aortic, esophageal, tracheal and colonic stents may have diameters up to about 25mm and lengths about 100 mm or longer. Vascular stents are generally shorter, typically about 10 to 60 mm in length, and often preferably about 1 2 to 25 mm in length. Such vascular stents are typically designed to expand to a diameter of about 2 to 6 mm when inserted into the vascular system of a patient, often preferably about 2 to 4 mm.
The structure 1 2 is composed of a base material 1 4 suitable for the intended use of the structure 1 2. The base material 1 4 is preferably biocompatible. A variety of conventional materials can be employed as the base material 14. Some materials may be more useful for structures other than the coronary stent exemplifying the structure 12. The base material 14 may be either elastic or inelastic as required for its intended use in the patient. The base material may be either biodegradable or nonbiodegradable, and a variety of biodegradable polymers are known. The base material 14 can also be porous or preferably non-porous, again based on its intended use or application.
Accordingly, the base material 1 4 can include at least one of stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, or another biocompatible metal, or alloys of any of these; carbon or carbon fiber; cellulose acetate, cellulose nitrate, silicone, polyethylene terephthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or another biocompatible polymeric material, or mixtures or copolymers of these; polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate or another biodegradable polymer, or mixtures or copolymers of these; a protein, an extracellular matrix component, collagen, fibrin or another biologic agent; or a suitable mixture of any of these. Stainless steel is particularly useful as the base material 14 when the structure 1 2 is configured as a vascular stent. In the practice of the present invention, however, particularly preferred base materials 14 include stainless steel, nitinol, tantalum, polylactic acid, polyglycolic acid and biodegradable materials. Molybdenum-rhenium alloy and magnesium may also possibly be useful base materials 1 4 as well.
Of course, when the structure 1 2 is composed of a radiolucent material such as polypropylene, polyethylene or others above, a conventional radiopaque marker or coating may and preferably should be applied to it at some limited location. The radiopaque marker or coating provides a means for identifying the location of the structure 1 2 by X-ray or fluoroscopy during or after its introduction into the patient's vascular system.
The base material 14 of the structure 12 of the medical device 10 of the present invention includes a roughened or textured surface 1 6 extending at least partly over the base material 14. The surface 1 6 is roughened or textured in a manner described in more detail below. While the surface 1 6 can be the entire surface of the base material 14, in the preferred embodiment of the present invention (where the structure 1 2 is configured as a vascular stent) the surface 1 6 is the outer surface of the base material 14.
The medical device 1 0 of the present invention further comprises at least
one layer 1 8 of a bioactive material posited directly upon the roughened or textured surface 1 6 of the base material 14 of the structure 1 2. The medical device 10 of the present invention is characterized in that it does not require or is free of any additional coating or layer atop the layer 1 8 of bioactive material. Although, it is to be understood that for any reason an additional coating or layer atop or below the layer 1 8 of bioactive is desired, such coating or layer can be applied and still be within the contemplation of the present invention. The layer 1 8 may be smoother or rougher than the roughened or textured surface 1 6.
The base material 14 of the structure 1 2 is preferably non-porous, although the structure 1 2 itself can be perforate. The difference between a porous material and a non-porous but perforate material is a practical one; the relatively smaller open cells of a porous material are of a character and number sufficient to retain an appreciable amount of an applied bioactive material therein, while the relatively larger perforations of a non-porous material are of a character and number which are not sufficient to retain an appreciable amount of an applied bioactive material therein. Alternatively, the open cells of a porous material can be considered generally microscopic, while perforations through a non-porous material can be considered generally macroscopic.
A vast range of drugs, medicants and materials can be employed as the bioactive material in the layer 1 8. Particularly useful in the practice of the present invention are materials which prevent or ameliorate abrupt closure and restenosis of blood vessels previously opened by stenting surgery or other procedures. Thrombolytics (which dissolve, break up or disperse thrombi) and antithrombogenics (which interfere with or prevent the formation of thrombi) are especially useful bioactive materials when the structure 1 2 is a vascular stent. Particularly preferred thrombolytics are urokinase, streptokinase and the tissue plasminogen activators. Particularly preferred antithrombogenics are heparin, hirudin and the antiplatelets.
Urokinase is a plasminogen activating enzyme typically obtained from human kidney cell cultures. Urokinase catalyzes the conversion of plasminogen into the fibrinolytic plasmin, which breaks down fibrin thrombi.
Heparin is a mucopolysaccharide anticoagulant typically obtained from
porcine intestinal mucosa or bovine lung. Heparin acts as a thrombin inhibitor by greatly enhancing the effects of the blood's endogenous antithrombin III. Thrombin, a potent enzyme in the coagulation cascade, is key in catalyzing the formation of fibrin. Therefore, by inhibiting thrombin, heparin inhibits the formation of fibrin thrombi.
Of course, bioactive materials having other functions can also be successfully delivered by the device 1 0 of the present invention. For example, an antiproliferative agent such as methotrexate will inhibit over-proliferation of smooth muscle cells and thus inhibit restenosis of the dilated segment of the blood vessel. Additionally, localized delivery of an antiproliferative agent is also useful for the treatment of a variety of malignant conditions characterized by highly vascular growth. In such cases, the device 1 0 of the present invention could be placed in the arterial supply of the tumor to provide a means of delivering a relatively high dose of the antiproliferative agent directly to the tumor.
A vasodilator such as a calcium channel blocker or a nitrate will suppress vasospasm, which is common following angioplasty procedures. Vasospasm occurs as a response to injury of a blood vessel, and the tendency toward vasospasm decreases as the vessel heals. Accordingly, the vasodilator is desirably supplied over a period of about two to three weeks. Of course, trauma from angioplasty is not the only vessel injury which can cause vasospasm, and the device 1 0 may be introduced into vessels other than the coronary arteries, such as the aorta, carotid arteries, renal arteries, iliac arteries or peripheral arteries for the prevention of vasospasm in them.
A variety of other bioactive materials are particularly suitable for use when the structure 1 2 is configured as something other than a coronary stent. For example, an anti-cancer chemotherapeutic agent can be delivered by the device 1 0 to a localized tumor. More particularly, the device 10 can be placed in an artery supplying blood to the tumor or elsewhere to deliver a relatively high and prolonged dose of the agent directly to the tumor, while limiting systemic exposure and toxicity. The agent may be a curative, a pre-operative debulker reducing the size of the tumor, or a palliative which eases the symptoms of the disease. It should be noted that the bioactive material in the present invention is delivered across the device 1 0, and not
by passage from an outside source through any lumen defined in the device 1 0, such as through a catheter employed for conventional chemotherapy. The bioactive material of the present invention may, of course, be released from the device 10 into any lumen defined in it, and that lumen may carry some other agent to be delivered through it.
Paclitaxel is a particularly preferred anti-cancer agent and/or anti- angiogenic agent as the bioactive material of the layer 1 8. The angiogenesis- dependent diseases are those diseases which require or induce vascular growth, for example, certain types of cancer. Estrogen and estrogen derivatives are also particularly preferred as the bioactive material of the layer 1 8.
Dopamine or a dopamine agonist such as bromocriptine mesylate or pergolide mesylate is useful for the treatment of neurological disorders such as Parkinson's disease. The device 1 0 could be placed in the vascular supply of the thalamic substantia nigra for this purpose, or elsewhere, localizing treatment in the thalamus.
The present invention also contemplates the use of bioactive materials which covalently bond to the roughened or textured surface 1 6 of the base material 14 of the structure 1 2.
It should be clear that a wide range of other bioactive materials can be delivered by the device 10. Accordingly, it is preferred that the bioactive material of the layer 18 comprises at least one of: paclitaxel; estrogen or estrogen derivatives; heparin or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L- poly-L-arginyl chloromethyl ketone, or another antithrombogenic agent, or mixtures thereof; urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof; a fibrinolytic agent; a vasospasm inhibitor; a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator; an antimicrobial agent or antibiotic; aspirin, ticlopdine or another antiplatelet agent; colchicine or another antimitotic, or another microtubule inhibitor; cytochalasin or another actin inhibitor; a remodelling inhibitor; deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention; GP llb/llla, GP Ib-IX or another inhibitor or surface glycoprotein receptor; methotrexate
or another antimetabolite or antiproliferative agent; an anti-cancer chemotherapeutic agent; dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid; an immunosuppressive agent (such as cyclosporin or rapamycine); an antibiotic (such as streptomycin, erythromycin or vancomycine); dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist; 60Co (having a half life of 5.3 years), 192lr (73.8 days), 32P (14.3 days), 111ln (68 hours), 90Y (64 hours), 99mTc (6 hours) or another radiotherapeutic agent; iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent; a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent; captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor; ascorbic acid, alphatocopherol, superoxide dismutase, deferoxyamine, a 21 -aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant; angiopeptin; a 1 C-, 3H- , 131l-, 32P- or 36S-radiolabelled form or other radiolabelled form of any of the foregoing; or a mixture of any of these.
When the structure 1 2 is configured as a vascular stent, however, particularly preferred materials for the bioactive material of the layer 1 8 are heparin, anti-inflammatory steroids including but not limited to dexamethasone and its derivatives, and mixtures of heparin and such steroids.
Other materials may possibly be useful as the bioactive material in the practice of the present invention, including: smooth muscle cell inhibitors, collagen inhibitors, anti-coagulants and cholesterol reducing agents; forskolin, vapiprost, prostaglandin and analogues thereof, prostacyclin and prostacyclin analogues, dextran and dipyridamole; angiotensin converting enzyme inhibitors such as Captopril® (available from Squibb), Cilazapril® (available from Hoffman-LaRoche), or Lisinopril® (available from Merck); fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, Lovastatin® (an inhibitor of HMG-CoA reductase, a cholesterol-lowering drug from Merck), methotrexate, monoclonal antibodies (such as to PDGF receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitor (available from Glaxo), vascular endothelial growth factor
(VEGF) or analogues thereof, various cell cycle inhibitors such as the protein product of the retinoblastoma tumor suppressor gene or analogues thereof), Seramin (a PDGF antagonist), serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), nitric oxide, alpha-interferon and genetically engineered epithelial cells.
The present invention is also directed to a method of manufacturing the medical device 10 disclosed above. More particularly, the method of the present invention first comprises providing a structure 1 2 adapted for the temporary or permanent introduction into a patient. The structure 1 2 comprises a preferably non- porous base material 14 having a surface 1 6 and is configured, for example, as a stent (such as a vascular stent) . The structure 1 2 and the base material 1 4 have been described in detail above, and for brevity, such details will not be repeated here. Stainless steel, nitinol, tantalum, polylactic acid, polyglycolic acid and biodegradable materials are particularly preferred as the base material 1 4 of the structure 1 2.
The method of the present invention further comprises the steps of attaining a desired roughness or texture on the surface 1 6 of the base material 14 of the structure 1 2, and positing a layer 1 8 of a bioactive material directly upon the roughened or textured surface 1 6 of the base material 14. A wide range of bioactive materials useful in the layer 1 8 has been disclosed in detail above; again, for brevity, such detail will not be repeated. Paclitaxel, a taxane or another paclitaxel analogue, estrogen and estrogen derivatives are particularly preferred as bioactive materials in the layer 1 8.
The method of manufacturing a medical device 10 according to the present invention is characterized in that the resulting medical device 10 does not require or is free of any additional coating or layer atop the layer 1 8 of bioactive material. The method of the present invention therefore does not include any steps in which the bioactive material is covered by or contained within a time-release or containment layer. While the method of the present invention contemplates the use of a base material 1 4 which itself comprises a plurality of layers or constituents, such an arrangement may not be preferred in the practice of the present invention. In any event, it would be the outermost one of such plural layers or constituents which
possesses the roughened or textured surface 1 6 on which the layer 1 8 of bioactive material is posited directly.
The step of directly positing the layer 1 8 of bioactive material on the roughened or textured surface 1 6 of the base material 1 4 can be carried out in any convenient manner. The structure 1 2 (or suitable portion thereof) can be dipped or soaked in an appropriate solution of the desired bioactive material, and the solvent of the solution evaporated to leave a layer 1 8 of the bioactive material on the roughened or textured surface 1 6 of the base material 14. Preferably, however, the positing step is carried out by spraying a solution of the bioactive material on the roughened or textured surface 1 6 of the base material 14 of the structure 1 2 and allowing the structure 1 2 to dry. While spraying may have a relatively low efficiency in transferring the bioactive material to the roughened or textured surface 1 6, it is adequate for the purposes of the present invention.
By way of example, paclitaxel (the particularly preferred bioactive material in the present invention) can be posited by spraying an ethanolic solution of it on the roughened or textured surface 1 6 of the base material 1 4. The solution conveniently contains about 2 to about 4 mg of paclitaxel per ml of ethanol. (The ethanol should be 100% USP grade or equivalent, not denatured alcohol or 95% ethanol.) Taking a stent of 1 5mm in length and 3 mm in diameter as typical, having a textured, gross outer surface area on the order of 25 mm2, spraying can be readily carried out to posit about 5 to about 500 μg, preferably 50 to 1 50 μg, of paclitaxel on the roughened or textured surface 1 6 of the base material 14. Perhaps less than about 1 % of the paclitaxel is ultimately posited from solution onto the textured surface 1 6. The selection of suitable solvents and concentrations for other bioactive materials, or the selection of other techniques for positing other bioactive materials directly upon the roughened or textured surface 1 6, should be well within the skill of those in the art in view of the present disclosure. Any experimentation required should be minimal, particularly in view of the extensive testing required before devices of this type can be distributed in the U.S.
The surface 1 6 of the base material 14 of the structure 1 2 can be roughened or textured in any convenient manner, such as by etching. Preferably,
however, the surface 1 6 is roughened or textured by abrading, for example, by abrading with an abrasive grit 24 comprising at least one of sodium bicarbonate (USP), calcium carbonate, aluminum oxide, colmanite (calcium borate), crushed glass, crushed walnut shells, or mixtures of these or other abrasive particulates. Such roughening or texturing is most easily carried out by placing the medical device 1 0 on a mandrel 20 in a position such that abrasive grit 24 delivered from a nozzle 22 impinges on the surface 1 6. The initial surface of the base material prior to roughening or texturing may be smoother than the desired surface roughness, or it may be even rougher.
The grit size and feed rate of the abrasive grit 24, the structure of the nozzle 22, the pressure at which the abrasive grit 24 is delivered from the nozzle 22, the distance of the surface 1 6 from the nozzle 22 and the rate of relative movement of the medical device 1 0 and the nozzle 22 are all factors to be considered in achieving an appropriate desired roughness or texture of the surface 1 6 of the base material 1 4 of the structure 1 2. By way of non-limiting example, when the base material 1 4 is stainless steel, the abrading step can be carried out with an abrasive grit 24 having a particle size of about 5 microns (5 μm) to about 500 microns (500 μm). More preferably, the abrading step is carried out with sodium bicarbonate (USP) having a nominal particle size of about 50 microns (50 μm), with approximately 50% greater than 40 microns (40 μm) and approximately 1 % greater than 1 50 microns (1 50 //m). Such abrading is preferably carried out with the sodium bicarbonate or other abrasive grit 24 delivered at a pressure under flow of about 5 to about 200 PSI (about 34 to about 1 380 KPa), most preferably about 100 PSI (about 690 KPa). Such abrading is also preferably carried out with the sodium bicarbonate or other abrasive grit 24 delivered at a grit feed rate of about 1 to about 1 000 g/min, most preferably about 1 0 to about 1 5 g/min.
The carrier gas or propellent for delivery of the abrasive grit is preferably nitrogen, air or argon, and most preferably nitrogen, although other gases may be suitable as well. When the medical device 1 0 is configured as disclosed above, the distance from the outlet of the nozzle 22 to the center of the mandrel 20 can be about 1 to about 1 00 mm. A preferred nozzle 22 is the Comco Microblaster; when
employed, the preferred distance from the outlet of the nozzle 22 to the center of the mandrel 20 is about 5 to about 10 mm. The Paasche LAC #3 is also useful as the nozzle 22.
To provide a uniform roughening or texturing of the surface 1 6 of the base material 14 of the structure 1 2, it is highly desirable that relative movement of the surface 1 6 and the nozzle 22 be provided during abrasion of the surface 1 6. Any pattern of motion which achieves the desired uniformity of roughness or texture may be employed. It is preferred that such motion entail both longitudinal or lengthwise movement along the structure 1 2 and circumferential movement or repositioning about the structure 1 2. Repeated longitudinal movement with repeated passes at different circumferential positions is most preferable. More particularly, abrading of the surface 1 6 can entail from 1 to about 50 axial passes per circumferential position, while the number of circumferential positions for such axial passes can range from about 4 to an unlimited number of circumferential positions. This last is achieved by continuous relative rotation of the surface 1 6 and the nozzle 22. The sweep rate of the nozzle 22 along the surface 1 6 can range from about 1 to about 70 mm/sec for the particular stent dimensions disclosed above.
When the base material 14 of the structure 1 2 is stainless steel, and the abrasive grit 24 is 50 micron sodium bicarbonate (USP), a particularly preferred combination of abrading conditions is:
Nozzle 22: Comco Microblaster
Propellant: Nitrogen gas
Pressure: 1 20 PSI (828 KPa) (under flow)
Spray plan: 8 equally-spaced circumferential positions 4 axial passes per circumferential position
Sweep rate: About 1 6 mm/sec
Grit feed rate: About 0.1 5 to 0.30 g/sec
Nozzle outlet to mandrel center: about 5 to 10 mm
When abrading is carried out in this manner, a roughened or textured surface 1 6 is obtained which is thought to have a mean surface roughness (that is,
a mean height of surface features) of about 10 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 1 00 //in. (about 25 nm and about 2.5 μm). Such a surface 1 6 is capable of retaining on it a highly substantial portion of bioactive material posited directly on it without requiring any additional covering or containment layer.
More particularly, the adhesion of paclitaxel to two types of stainless steel, grit abraded stents was compared to its adhesion to stents of those types whose surfaces had instead been plasma treated prior to the direct deposition of paclitaxel thereon (control stents). The coated stents of both types, that is, medical devices 1 0 of the present invention and control stents, were then subjected to a physical adhesion test which simulated the rate at which paclitaxel would be delivered during introduction and deployment of the stents in clinical use. The adhesion test involved passing each stent through a water-filled guiding catheter of appropriate diameter and inflating the balloon catheter to expand each stent to its intended diameter. The stents are already mounted before coating. The amount of paclitaxel remaining on each stent was then measured by spectrometry and compared to the amount of paclitaxel initially posited on each stent. Stents having surfaces 1 6 roughened or textured by abrasion with different abrasive grits 24 retained 84.1 ± 10.2% of the paclitaxel originally applied, while stents having plasma treated surfaces retained only 44.3 ± 8.7% of the paclitaxel originally applied (p <0.0001 ). This appears to demonstrate the successful retention of the layer 1 8 of bioactive material on the roughened or textured surface 1 6 of the base material 1 4 of the structure 1 2 of the medical device 10 of the present invention.
In view of the foregoing disclosure, those skilled in the art should readily be able to perform any trial-and-error testing to obtain the optimal processing conditions for any desired combination of particular base materials 14 and bioactive materials. Such testing simply requires roughening or texturing the surface 1 6 of a particular base material 14 in a selected manner, applying a layer 1 8 of a particular bioactive material to the roughened or textured surface 1 6 and measuring the retention of bioactive material on the roughened or textured surface 1 6 after clinical introduction and deployment has been mimicked.
It should be clear that the present invention provides a medical device 10 and method for manufacturing the same which is particularly advantageous over prior devices and methods for making such devices. The time and cost of manufacture of the medical device of the present invention are minimized by the absence of any steps to incorporate the bioactive material in a containment layer, or to apply a containment or time-release layer over the bioactive material. The particularly preferred use of sodium bicarbonate as the abrasive to provide roughness or texture to the surface of the base material of the structure is advantageous in the low toxicity of the sodium bicarbonate to production workers, the ease of product and waste cleanup, and the biocompatibility of any residual sodium bicarbonate. These are important advantages in their own right, but incidentally also reduce the time and cost for manufacture of the medical device 1 0.
The details of the construction or composition of the various elements of the medical device 1 0 of the present invention not otherwise disclosed are not believed to be critical to the achievement of the advantages of the present invention, so long as the elements possess the strength or mechanical properties needed for them to perform as disclosed. The selection of any such details of construction are believed to be well within the ability of one of even rudimentary skills in this area, in view of the present disclosure. For practical reasons, however, most embodiments of the medical device 10 of the present invention should probably be considered to be single-use devices, rather than being reusable.
Industrial Applicability
The present invention is useful in the performance of various surgical procedures and in the manufacture of devices for the performance of various surgical procedures, and therefore finds applicability in human and veterinary medicine.
It is to be understood, however, that the above-described device is merely an illustrative embodiment of the principles of this invention, and that other devices and methods for using them may be devised by those skilled in the art, without departing from the spirit and scope of the invention. It is also to be understood that the invention is directed to embodiments both comprising and consisting of the
disclosed parts. In particular, it is contemplated that only part of a medical device 1 0 according to the present invention need be coated with bioactive material. It is further contemplated that different parts of a medical device 1 0 could be coated with different bioactive materials.
It is also to be understood that various parts, recesses, portions, sides, segments, channels, and the like of the device can be posited with the bioactive material either singly or in combination with other bioactive, coating, or layering materials. This can be done to further control the release of the bioactive material to the delivery site. Such configurations are contemplated and disclosed in U.S. Patents No. 5,380,299; 5,609,629; 5,824,049; 5,873,904; 6,096,070; 6,299,604 and are incorporated by reference herein. Likewise, presently pending patent applications claiming priority to these patents such as Serial Nos. 08/956,71 5; 09/027,054; and 09/850,691 are also contemplated and incorporated by reference herein.
As previously suggested, the medical device of the present invention can also include channels, grooves, recesses, indentations, projections, buildups, and the like to increase the surface area of the device to which the bioactive material can be posited therein.
Claims (20)
1 . A medical device for introduction into a patient, wherein at least part of the surface of the device is treated to produce a roughened, uneven, unsmooth, or textured surface, and wherein bioactive material is formed on at least said part of the surface.
2. The medical device according to claim 1 , wherein the degree of treatment is controlled to provide sufficient adhesion of the bioactive material to the surface.
3. A medical device comprising: a structure adapted for introduction into a patient, the structure comprising a base material having at least one of a roughened, uneven, unsmooth, or textured surface; and a layer of a bioactive material posited directly upon the at least one surface of the base material of the structure.
4. The medical device according to claim 3, wherein the base material of the structure comprises at least one of: stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, or another biocompatible metal, or alloys of any of these; carbon or carbon fiber; cellulose acetate, cellulose nitrate, silicone, polyethylene terephthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or another biocompatible polymeric material, or mixtures or copolymers of these; polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate or another biodegradable polymer, or mixtures or copolymers of these; a protein, an extracellular matrix component, collagen, fibrin or another biologic agent; or a suitable mixture of any of these.
5. The medical device according to claim 3, wherein the bioactive material of the layer comprises at least one of: paclitaxel, a taxane or other paclitaxel analogue; estrogen or estrogen derivatives; heparin or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L-poly-L-arginyl chloromethyl ketone, or another antithrombogenic agent, or mixtures thereof; urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof; a fibrinolytic agent; a vasospasm inhibitor; a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator; an antimicrobial agent or antibiotic; aspirin, ticlopdine or another antiplatelet agent; vascular endothelial growth factor (VEGF) or analogues thereof; colchicine or another antimitotic, or another microtubule inhibitor; cytochalasin or another actin inhibitor; a remodeling inhibitor; deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention; a cell cycle inhibitor (such as the protein product of the retinoblastoma tumor suppressor gene, or analogues thereof); GP llb/llla, GP Ib-IX or another inhibitor or surface glycoprotein receptor; methotrexate or another antimetabolite or antiproliferative agent; an anti-cancer chemotherapeutic agent; dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid; prostaglandin, prostacyclin or analogues thereof; an immunosuppressive agent (such as cyclosporine or rapamycin); an antibiotic (such as streptomycin), erythromycin or vancomycin; dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist; 60Co, 192lr, 32P, 1 1 ln, 90Y, 99mTc or another radiotherapeutic agent; iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent; a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent; captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor; ascorbic acid, alphatocopherol, superoxide dismutase, deferoxyamine, a 21 - aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant; angiopeptin; a 14C-, 3H-, 131l-, 32P- or 36S-radiolabelled form or other radiolabelled form of any of the foregoing; or a mixture of any of these.
6. The medical device according to claim 3, wherein the at least one surface of the base material of the structure has a mean surface roughness of about 1 0 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 100 //in. (about 25 nm and about 2.5 μm).
7. The medical device according to claim 3, wherein the medical device does not require or is free of any additional coating or layer atop the layer of bioactive material.
8. A medical device comprising: a structure adapted for introduction into a patient, the structure comprising a base material having at least one of a roughened, uneven, unsmooth, or textured surface, the structure being configured as a vascular stent and the base material comprising at least one of stainless steel, nitinol, and an alloy of nickel and titanium; and a layer of a bioactive material posited directly upon the at least one surface of the base material of the structure, the bioactive material comprising paclitaxel; wherein the medical device does not require any additional coating or layer atop the layer of bioactive material; and wherein the at least one surface of the base material of the structure has a mean surface roughness of about 10 //in. (about 250 nm) and a surface roughness range between about 1 / in. and about 100 //in. (about 25 nm and about 2.5 μm).
9. A method of manufacturing a medical device comprising the steps of: providing a structure adapted for introduction into a patient, the structure comprising a base material having a surface; roughening or texturing the surface of the base material of the structure; and positing a layer of a bioactive material directly upon the roughened or textured surface of the base material of the structure; the method being characterized in that the resulting medical device does not require any additional coating or layer atop the layer of bioactive material.
10. The method according to claim 8, wherein the method is carried out with a base material comprising at least one of: stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, or another biocompatible metal, or alloys of any of these; carbon or carbon fiber; cellulose acetate, cellulose nitrate, silicone, polyethylene terephthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or another biocompatible polymeric material, or mixtures or copolymers of these; polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate or another biodegradable polymer, or mixtures or copolymers of these; a protein, an extracellular matrix component, collagen, fibrin or another biologic agent; or a suitable mixture of any of these.
1 1 . The method according to claim 8, wherein the method is carried out with a bioactive material of the layer comprising at least one of: paclitaxel, a taxane or a paclitaxel analogue or derivative; estrogen or estrogen derivatives; heparin or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L-poly-L-arginyl chloromethyl ketone, or another antithrombogenic agent, or mixtures thereof; urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof; a fibrinolytic agent; a vasospasm inhibitor; a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator; an antimicrobial agent or antibiotic; aspirin, ticlopdine or another antiplatelet agent; colchicine or another antimitotic, or another microtubule inhibitor; cytochalasin or another actin inhibitor; a remodeling inhibitor; deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention; GP llb/llla, GP Ib-IX or another inhibitor or surface glycoprotein receptor; methotrexate or another antimetabolite or antiproliferative agent; an anti-cancer chemotherapeutic agent; dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid; dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist; 60Co, 192lr, 32P, 111ln, 90Y, 99mTc or another radiotherapeutic agent; iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent; a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent; captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor; ascorbic acid, alphatocopherol, superoxide dismutase, deferoxyamine, a 21 -aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant; angiopeptin; a 14C-, 3H-, 131 l-, 32P- or 36S-radiolabelled form or other radiolabelled form of any of the foregoing; or a mixture of any of these.
1 2. The method according to claim 9, wherein the positing step is carried out by spraying a solution of the bioactive material on the roughened or textured surface of the base material of the structure.
1 3. The method according to claim 9, wherein the roughening or texturing step is carried out by abrading the surface of the base material of the structure.
14. The method according to claim 1 3, wherein the abrading is carried out with an abrasive grit comprising at least one of sodium bicarbonate, calcium carbonate, aluminum oxide, colmanite, crushed glass or crushed walnut shells.
1 5. The method according to claim 1 3, wherein the abrading is carried out with an abrasive grit having a particle size of about 5 microns (5 μm) to about 500 microns (500 μm).
1 6. The method according to claim 1 3, wherein the abrading is carried out with sodium bicarbonate having a nominal particle size of about 50 microns (50 μm).
1 7. The method according to claim 1 3, wherein the abrading is carried out with an abrasive grit delivered at a pressure under flow of about 5 to about 200 PSI (about 34 to about 1 380 KPa).
1 8. The method according to claim 1 3, wherein the abrading is carried out with an abrasive grit delivered at a grit feed rate of about 1 to about 1000 g/min.
1 9. The method according to claim 1 3, wherein the abrading is carried out so as to yield a roughened or textured surface on the base material of the structure having a mean surface roughness of about 1 0 //in. (about 250 nm) and a surface roughness range between about 1 //in. and about 1 00 //in. (about 25 nm and about 2.5 μm).
20. The product of the method of claim 9.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111032098A (en) * | 2017-08-01 | 2020-04-17 | 株式会社多磨生物科技 | Medical sheet |
Families Citing this family (283)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5843089A (en) * | 1990-12-28 | 1998-12-01 | Boston Scientific Corporation | Stent lining |
US7846202B2 (en) * | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
US6774278B1 (en) * | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
US7867275B2 (en) | 1995-06-07 | 2011-01-11 | Cook Incorporated | Coated implantable medical device method |
US7550005B2 (en) | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
US20060052757A1 (en) * | 1996-06-04 | 2006-03-09 | Vance Products Incorporated, D/B/A Cook Urological Incorporated | Implantable medical device with analgesic or anesthetic |
US20060025726A1 (en) * | 1996-06-04 | 2006-02-02 | Vance Products Incorporated, D/B/A Cook Urological Incorporated | Implantable medical device with pharmacologically active layer |
US20060030826A1 (en) * | 1996-06-04 | 2006-02-09 | Vance Products Incorporated,d/b/a Cook Urological Incorporated | Implantable medical device with anti-neoplastic drug |
US6890546B2 (en) | 1998-09-24 | 2005-05-10 | Abbott Laboratories | Medical devices containing rapamycin analogs |
US20030129215A1 (en) * | 1998-09-24 | 2003-07-10 | T-Ram, Inc. | Medical devices containing rapamycin analogs |
US8057816B2 (en) * | 1997-09-26 | 2011-11-15 | Abbott Laboratories | Compositions and methods of administering paclitaxel with other drugs using medical devices |
US8257726B2 (en) * | 1997-09-26 | 2012-09-04 | Abbott Laboratories | Compositions, systems, kits, and methods of administering rapamycin analogs with paclitaxel using medical devices |
US7637948B2 (en) | 1997-10-10 | 2009-12-29 | Senorx, Inc. | Tissue marking implant |
US8668737B2 (en) | 1997-10-10 | 2014-03-11 | Senorx, Inc. | Tissue marking implant |
US6395019B2 (en) | 1998-02-09 | 2002-05-28 | Trivascular, Inc. | Endovascular graft |
US7713297B2 (en) | 1998-04-11 | 2010-05-11 | Boston Scientific Scimed, Inc. | Drug-releasing stent with ceramic-containing layer |
US20020099438A1 (en) | 1998-04-15 | 2002-07-25 | Furst Joseph G. | Irradiated stent coating |
US20030040790A1 (en) | 1998-04-15 | 2003-02-27 | Furst Joseph G. | Stent coating |
US7947015B2 (en) * | 1999-01-25 | 2011-05-24 | Atrium Medical Corporation | Application of a therapeutic substance to a tissue location using an expandable medical device |
US6955661B1 (en) | 1999-01-25 | 2005-10-18 | Atrium Medical Corporation | Expandable fluoropolymer device for delivery of therapeutic agents and method of making |
US7572245B2 (en) | 2003-09-15 | 2009-08-11 | Atrium Medical Corporation | Application of a therapeutic substance to a tissue location using an expandable medical device |
US6725083B1 (en) | 1999-02-02 | 2004-04-20 | Senorx, Inc. | Tissue site markers for in VIVO imaging |
US7983734B2 (en) | 2003-05-23 | 2011-07-19 | Senorx, Inc. | Fibrous marker and intracorporeal delivery thereof |
US7651505B2 (en) | 2002-06-17 | 2010-01-26 | Senorx, Inc. | Plugged tip delivery for marker placement |
US20090030309A1 (en) | 2007-07-26 | 2009-01-29 | Senorx, Inc. | Deployment of polysaccharide markers |
US9820824B2 (en) | 1999-02-02 | 2017-11-21 | Senorx, Inc. | Deployment of polysaccharide markers for treating a site within a patent |
US8361082B2 (en) | 1999-02-02 | 2013-01-29 | Senorx, Inc. | Marker delivery device with releasable plug |
US6862470B2 (en) | 1999-02-02 | 2005-03-01 | Senorx, Inc. | Cavity-filling biopsy site markers |
US8498693B2 (en) | 1999-02-02 | 2013-07-30 | Senorx, Inc. | Intracorporeal marker and marker delivery device |
US6575991B1 (en) | 1999-06-17 | 2003-06-10 | Inrad, Inc. | Apparatus for the percutaneous marking of a lesion |
US20030070676A1 (en) * | 1999-08-05 | 2003-04-17 | Cooper Joel D. | Conduits having distal cage structure for maintaining collateral channels in tissue and related methods |
US7220276B1 (en) * | 2000-03-06 | 2007-05-22 | Surmodics, Inc. | Endovascular graft coatings |
US6719991B2 (en) * | 2000-06-09 | 2004-04-13 | Baylor College Of Medicine | Combination of antimicrobial agents and bacterial interference to coat medical devices |
US6506408B1 (en) * | 2000-07-13 | 2003-01-14 | Scimed Life Systems, Inc. | Implantable or insertable therapeutic agent delivery device |
DE60135352D1 (en) | 2000-08-30 | 2008-09-25 | Univ Johns Hopkins | DEVICE FOR INTRA-OCCULAR ACTIVE AGGREGATION |
AU2002239290A1 (en) | 2000-11-20 | 2002-06-03 | Senorx, Inc. | Tissue site markers for in vivo imaging |
ES2640787T3 (en) | 2001-02-19 | 2017-11-06 | Novartis Ag | Combination of a derivative of rapamycin and letrozole to treat breast cancer |
US20020138136A1 (en) * | 2001-03-23 | 2002-09-26 | Scimed Life Systems, Inc. | Medical device having radio-opacification and barrier layers |
DE10115740A1 (en) | 2001-03-26 | 2002-10-02 | Ulrich Speck | Preparation for restenosis prophylaxis |
US6764505B1 (en) * | 2001-04-12 | 2004-07-20 | Advanced Cardiovascular Systems, Inc. | Variable surface area stent |
US7727221B2 (en) | 2001-06-27 | 2010-06-01 | Cardiac Pacemakers Inc. | Method and device for electrochemical formation of therapeutic species in vivo |
US7008446B1 (en) * | 2001-08-17 | 2006-03-07 | James Peter Amis | Thermally pliable and carbon fiber stents |
US7708712B2 (en) | 2001-09-04 | 2010-05-04 | Broncus Technologies, Inc. | Methods and devices for maintaining patency of surgically created channels in a body organ |
DE60238422D1 (en) * | 2001-09-24 | 2011-01-05 | Boston Scient Ltd | OPTIMIZED DOSAGE IN PACLITAXELIC STENTS |
US8740973B2 (en) | 2001-10-26 | 2014-06-03 | Icon Medical Corp. | Polymer biodegradable medical device |
EP1842567A3 (en) * | 2001-11-08 | 2008-01-02 | Atrium Medical Corporation | Intraluminal device with a coating containing a therapeutic agent |
US7125464B2 (en) | 2001-12-20 | 2006-10-24 | Boston Scientific Santa Rosa Corp. | Method for manufacturing an endovascular graft section |
US7147661B2 (en) | 2001-12-20 | 2006-12-12 | Boston Scientific Santa Rosa Corp. | Radially expandable stent |
US20030225451A1 (en) * | 2002-01-14 | 2003-12-04 | Rangarajan Sundar | Stent delivery system, device, and method for coating |
US20050178584A1 (en) * | 2002-01-22 | 2005-08-18 | Xingwu Wang | Coated stent and MR imaging thereof |
US20030215526A1 (en) * | 2002-03-08 | 2003-11-20 | Scott Stofik | Stable formulations of angiotensin converting enzyme (ACE) inhibitors |
US8728510B1 (en) * | 2002-03-15 | 2014-05-20 | Advanced Cardiovascular Systems, Inc. | Biocompatible carrier containing a bioadhesive material |
US8313760B2 (en) | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
ATE515277T1 (en) | 2002-05-24 | 2011-07-15 | Angiotech Int Ag | COMPOSITIONS AND METHODS FOR COATING MEDICAL IMPLANTS |
WO2004006976A1 (en) | 2002-07-12 | 2004-01-22 | Cook Incorporated | Coated medical device |
DE10244847A1 (en) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medical device for drug delivery |
DE60226236T3 (en) † | 2002-09-20 | 2011-12-15 | Abbott Laboratories Vascular Enterprises Ltd. | A rough-surfaced stent and its manufacturing process |
US20040148016A1 (en) * | 2002-11-07 | 2004-07-29 | Klein Dean A. | Biocompatible medical device coatings |
US20060036158A1 (en) | 2003-11-17 | 2006-02-16 | Inrad, Inc. | Self-contained, self-piercing, side-expelling marking apparatus |
ES2393780T3 (en) * | 2002-12-16 | 2012-12-28 | Ge Healthcare As | Magnetic resonance imaging procedure and compounds for use in the procedure |
US8066854B2 (en) * | 2002-12-18 | 2011-11-29 | Metascape Llc | Antimicrobial coating methods |
KR100495875B1 (en) * | 2003-01-18 | 2005-06-16 | 사회복지법인 삼성생명공익재단 | Stent for percutaneous coronary intervention coated with drugs for the prevention of vascular restenosis |
US6699282B1 (en) | 2003-03-06 | 2004-03-02 | Gelsus Research And Consulting, Inc. | Method and apparatus for delivery of medication |
CA2518872A1 (en) * | 2003-03-28 | 2004-10-14 | Kosan Biosciences, Inc. | Devices, methods, and compositions to prevent restenosis |
US20040230176A1 (en) * | 2003-04-23 | 2004-11-18 | Medtronic Vascular, Inc. | System for treating a vascular condition that inhibits restenosis at stent ends |
JP4824549B2 (en) | 2003-05-02 | 2011-11-30 | サーモディクス,インコーポレイティド | Controlled release bioactive substance delivery device |
US8246974B2 (en) | 2003-05-02 | 2012-08-21 | Surmodics, Inc. | Medical devices and methods for producing the same |
US7877133B2 (en) | 2003-05-23 | 2011-01-25 | Senorx, Inc. | Marker or filler forming fluid |
WO2005006963A2 (en) | 2003-07-18 | 2005-01-27 | Broncus Technologies, Inc. | Devices for maintaining patency of surgically created channels in tissue |
US8308682B2 (en) | 2003-07-18 | 2012-11-13 | Broncus Medical Inc. | Devices for maintaining patency of surgically created channels in tissue |
US8021331B2 (en) * | 2003-09-15 | 2011-09-20 | Atrium Medical Corporation | Method of coating a folded medical device |
JP2007505655A (en) * | 2003-09-15 | 2007-03-15 | アトリウム メディカル コーポレーション | Application of therapeutic substances to tissue sites using porous medical devices |
US7744587B2 (en) * | 2003-09-22 | 2010-06-29 | Boston Scientific Scimed, Inc. | Surface modified reinforcing member for medical device and method for making same |
US20050273002A1 (en) | 2004-06-04 | 2005-12-08 | Goosen Ryan L | Multi-mode imaging marker |
US7803178B2 (en) | 2004-01-30 | 2010-09-28 | Trivascular, Inc. | Inflatable porous implants and methods for drug delivery |
EP1568394A1 (en) * | 2004-02-26 | 2005-08-31 | Muijs van de Moer, Wouter Matthijs | Coated electrode |
US8409167B2 (en) | 2004-07-19 | 2013-04-02 | Broncus Medical Inc | Devices for delivering substances through an extra-anatomic opening created in an airway |
US20060039950A1 (en) * | 2004-08-23 | 2006-02-23 | Zhengrong Zhou | Multi-functional biocompatible coatings for intravascular devices |
US7901451B2 (en) | 2004-09-24 | 2011-03-08 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
WO2006036983A2 (en) | 2004-09-28 | 2006-04-06 | Atrium Medical Corporation | Pre-dried drug delivery coating for use with a stent |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US9801982B2 (en) | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US8312836B2 (en) | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
US8124127B2 (en) | 2005-10-15 | 2012-02-28 | Atrium Medical Corporation | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
US20060067976A1 (en) | 2004-09-28 | 2006-03-30 | Atrium Medical Corporation | Formation of barrier layer |
US20060083768A1 (en) * | 2004-09-28 | 2006-04-20 | Atrium Medical Corporation | Method of thickening a coating using a drug |
KR101052778B1 (en) * | 2004-11-11 | 2011-08-01 | 삼성전자주식회사 | Clothes dryer and dryness detection method |
US7455688B2 (en) * | 2004-11-12 | 2008-11-25 | Con Interventional Systems, Inc. | Ostial stent |
US9339403B2 (en) * | 2004-11-12 | 2016-05-17 | Icon Medical Corp. | Medical adhesive for medical devices |
US8419656B2 (en) | 2004-11-22 | 2013-04-16 | Bard Peripheral Vascular, Inc. | Post decompression marker introducer system |
US8323333B2 (en) | 2005-03-03 | 2012-12-04 | Icon Medical Corp. | Fragile structure protective coating |
US7452501B2 (en) * | 2005-03-03 | 2008-11-18 | Icon Medical Corp. | Metal alloy for a stent |
US7540995B2 (en) * | 2005-03-03 | 2009-06-02 | Icon Medical Corp. | Process for forming an improved metal alloy stent |
US20060198869A1 (en) * | 2005-03-03 | 2006-09-07 | Icon Medical Corp. | Bioabsorable medical devices |
AU2006221046B2 (en) * | 2005-03-03 | 2012-02-02 | Icon Medical Corp. | Improved metal alloys for medical device |
US9107899B2 (en) | 2005-03-03 | 2015-08-18 | Icon Medical Corporation | Metal alloys for medical devices |
JP2008532643A (en) * | 2005-03-09 | 2008-08-21 | ザ ユニバーシティー オブ テネシー リサーチ ファウンデーション | Barrier stent and use thereof |
US10357328B2 (en) | 2005-04-20 | 2019-07-23 | Bard Peripheral Vascular, Inc. and Bard Shannon Limited | Marking device with retractable cannula |
CA2613108A1 (en) * | 2005-06-30 | 2007-01-11 | Mc3, Inc. | Nitric oxide coatings for medical devices |
WO2007005759A2 (en) * | 2005-06-30 | 2007-01-11 | Mc3, Inc. | Analyte sensors and compositions for use therein |
WO2007024649A2 (en) * | 2005-08-19 | 2007-03-01 | X-Cell Medical Incorporated | Methods of treating and preventing acute myocardial infarction |
US20070073390A1 (en) * | 2005-09-23 | 2007-03-29 | Medlogics Device Corporation | Methods and devices for enhanced adhesion between metallic substrates and bioactive material-containing coatings |
US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
CA2562580C (en) | 2005-10-07 | 2014-04-29 | Inrad, Inc. | Drug-eluting tissue marker |
CN101378792A (en) * | 2005-12-02 | 2009-03-04 | 密执安大学评议会 | Polymer compositions, coatings and devices, and methods of making and using the same |
US7914573B2 (en) * | 2005-12-13 | 2011-03-29 | Cordis Corporation | Polymeric stent having modified molecular structures |
US20070154518A1 (en) * | 2005-12-29 | 2007-07-05 | Robert Falotico | Photoactive biocompatible coating composition |
US7919108B2 (en) * | 2006-03-10 | 2011-04-05 | Cook Incorporated | Taxane coatings for implantable medical devices |
US20080286325A1 (en) * | 2006-01-05 | 2008-11-20 | Med Institute, Inc. | Cyclodextrin elution media for medical device coatings comprising a taxane therapeutic agent |
US8840660B2 (en) | 2006-01-05 | 2014-09-23 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
US8089029B2 (en) | 2006-02-01 | 2012-01-03 | Boston Scientific Scimed, Inc. | Bioabsorbable metal medical device and method of manufacture |
EP1832289A3 (en) * | 2006-03-08 | 2007-12-12 | Sahajanand Medical Technologies PVT. ltd | Compositions and coatings for implantable medical devices |
US7875284B2 (en) * | 2006-03-10 | 2011-01-25 | Cook Incorporated | Methods of manufacturing and modifying taxane coatings for implantable medical devices |
US20070224235A1 (en) | 2006-03-24 | 2007-09-27 | Barron Tenney | Medical devices having nanoporous coatings for controlled therapeutic agent delivery |
US8187620B2 (en) | 2006-03-27 | 2012-05-29 | Boston Scientific Scimed, Inc. | Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents |
US8048150B2 (en) | 2006-04-12 | 2011-11-01 | Boston Scientific Scimed, Inc. | Endoprosthesis having a fiber meshwork disposed thereon |
US8303648B2 (en) * | 2006-04-25 | 2012-11-06 | Cook Medical Technologies Llc | Artificial venous valve containing therapeutic agent |
US9259535B2 (en) | 2006-06-22 | 2016-02-16 | Excelsior Medical Corporation | Antiseptic cap equipped syringe |
US11229746B2 (en) | 2006-06-22 | 2022-01-25 | Excelsior Medical Corporation | Antiseptic cap |
JP2009540926A (en) * | 2006-06-22 | 2009-11-26 | ウィルソン−クック・メディカル・インコーポレーテッド | Self-cleaning stent |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
JP2009542359A (en) | 2006-06-29 | 2009-12-03 | ボストン サイエンティフィック リミテッド | Medical device with selective covering |
US7722665B2 (en) * | 2006-07-07 | 2010-05-25 | Graft Technologies, Inc. | System and method for providing a graft in a vascular environment |
WO2008017028A2 (en) | 2006-08-02 | 2008-02-07 | Boston Scientific Scimed, Inc. | Endoprosthesis with three-dimensional disintegration control |
WO2008033711A2 (en) | 2006-09-14 | 2008-03-20 | Boston Scientific Limited | Medical devices with drug-eluting coating |
CA2663220A1 (en) | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Medical devices and methods of making the same |
EP2081616B1 (en) | 2006-09-15 | 2017-11-01 | Boston Scientific Scimed, Inc. | Bioerodible endoprostheses and methods of making the same |
CA2663271A1 (en) | 2006-09-15 | 2008-03-20 | Boston Scientific Limited | Bioerodible endoprostheses and methods of making the same |
ATE516827T1 (en) | 2006-09-15 | 2011-08-15 | Boston Scient Scimed | BIOLOGICALLY ERODABLE ENDOPROSTHESIS WITH BIOSTABLE INORGANIC LAYERS |
WO2008036548A2 (en) | 2006-09-18 | 2008-03-27 | Boston Scientific Limited | Endoprostheses |
WO2008039319A2 (en) * | 2006-09-25 | 2008-04-03 | Boston Scientific Scimed, Inc. | Injection of therapeutic into porous regions of a medical device |
US8101091B2 (en) * | 2006-10-02 | 2012-01-24 | Greatbatch Ltd. | Introducer assembly and method for forming an introducer assembly |
US8067055B2 (en) * | 2006-10-20 | 2011-11-29 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method of use |
US20080097591A1 (en) | 2006-10-20 | 2008-04-24 | Biosensors International Group | Drug-delivery endovascular stent and method of use |
WO2008051749A2 (en) | 2006-10-23 | 2008-05-02 | C. R. Bard, Inc. | Breast marker |
US20080103584A1 (en) * | 2006-10-25 | 2008-05-01 | Biosensors International Group | Temporal Intraluminal Stent, Methods of Making and Using |
US9492596B2 (en) | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
EP2083875B1 (en) | 2006-11-06 | 2013-03-27 | Atrium Medical Corporation | Coated surgical mesh |
US7981150B2 (en) | 2006-11-09 | 2011-07-19 | Boston Scientific Scimed, Inc. | Endoprosthesis with coatings |
WO2008060973A1 (en) * | 2006-11-10 | 2008-05-22 | Vance Products Incorporated D/B/A Cook Urological Incorporated | Graft for hysterotomy closure |
US9700704B2 (en) | 2006-11-20 | 2017-07-11 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US8414910B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8414909B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8425459B2 (en) | 2006-11-20 | 2013-04-23 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent |
US8414526B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids |
US8998846B2 (en) | 2006-11-20 | 2015-04-07 | Lutonix, Inc. | Drug releasing coatings for balloon catheters |
US8414525B2 (en) | 2006-11-20 | 2013-04-09 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US9737640B2 (en) | 2006-11-20 | 2017-08-22 | Lutonix, Inc. | Drug releasing coatings for medical devices |
US8430055B2 (en) | 2008-08-29 | 2013-04-30 | Lutonix, Inc. | Methods and apparatuses for coating balloon catheters |
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 |
EP3542748B1 (en) | 2006-12-12 | 2023-08-16 | C. R. Bard, Inc. | Multiple imaging mode tissue marker |
US8401622B2 (en) | 2006-12-18 | 2013-03-19 | C. R. Bard, Inc. | Biopsy marker with in situ-generated imaging properties |
JP5355418B2 (en) | 2006-12-28 | 2013-11-27 | ボストン サイエンティフィック リミテッド | Bioerodible endoprosthesis and method for manufacturing the bioerodible endoprosthesis |
AU2008207191B2 (en) | 2007-01-21 | 2011-02-24 | Hemoteq Ag | Medical product for treating stenosis of body passages and for preventing threatening restenosis |
EP2125058B1 (en) * | 2007-02-07 | 2014-12-03 | Cook Medical Technologies LLC | Medical device coatings for releasing a therapeutic agent at multiple rates |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
US8070797B2 (en) | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
TWI367147B (en) * | 2007-04-03 | 2012-07-01 | Tara Technologies | An apparatus, method and computer program product for modifying a surface of a component |
US8067054B2 (en) | 2007-04-05 | 2011-11-29 | Boston Scientific Scimed, Inc. | Stents with ceramic drug reservoir layer and methods of making and using the same |
US7976915B2 (en) | 2007-05-23 | 2011-07-12 | Boston Scientific Scimed, Inc. | Endoprosthesis with select ceramic morphology |
US20100070020A1 (en) | 2008-06-11 | 2010-03-18 | Nanovasc, Inc. | Implantable Medical Device |
US9192697B2 (en) | 2007-07-03 | 2015-11-24 | Hemoteq Ag | Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis |
US8002823B2 (en) | 2007-07-11 | 2011-08-23 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7942926B2 (en) | 2007-07-11 | 2011-05-17 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
WO2009012353A2 (en) | 2007-07-19 | 2009-01-22 | Boston Scientific Limited | Endoprosthesis having a non-fouling surface |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
US7931683B2 (en) | 2007-07-27 | 2011-04-26 | Boston Scientific Scimed, Inc. | Articles having ceramic coated surfaces |
WO2009018340A2 (en) | 2007-07-31 | 2009-02-05 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
JP2010535541A (en) | 2007-08-03 | 2010-11-25 | ボストン サイエンティフィック リミテッド | Coating for medical devices with large surface area |
US20090041727A1 (en) * | 2007-08-08 | 2009-02-12 | Conjugon, Inc. | Compositions and Methods for Microbe Storage and Delivery |
US8052745B2 (en) | 2007-09-13 | 2011-11-08 | Boston Scientific Scimed, Inc. | Endoprosthesis |
EP2205292B1 (en) | 2007-09-21 | 2013-05-15 | Boston Scientific Scimed, Inc. | Therapeutic agent-eluting medical devices having textured polymeric surfaces |
US8066755B2 (en) | 2007-09-26 | 2011-11-29 | Trivascular, Inc. | System and method of pivoted stent deployment |
US8663309B2 (en) | 2007-09-26 | 2014-03-04 | Trivascular, Inc. | Asymmetric stent apparatus and method |
US8226701B2 (en) | 2007-09-26 | 2012-07-24 | Trivascular, Inc. | Stent and delivery system for deployment thereof |
JP5356239B2 (en) | 2007-09-28 | 2013-12-04 | テルモ株式会社 | In vivo indwelling |
BRPI0817488A2 (en) | 2007-10-04 | 2017-05-16 | Trivascular Inc | low percutaneous profile modular vascular graft |
US7938855B2 (en) | 2007-11-02 | 2011-05-10 | Boston Scientific Scimed, Inc. | Deformable underlayer for stent |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8029554B2 (en) | 2007-11-02 | 2011-10-04 | Boston Scientific Scimed, Inc. | Stent with embedded material |
US8083789B2 (en) | 2007-11-16 | 2011-12-27 | Trivascular, Inc. | Securement assembly and method for expandable endovascular device |
US8328861B2 (en) | 2007-11-16 | 2012-12-11 | Trivascular, Inc. | Delivery system and method for bifurcated graft |
US7833266B2 (en) * | 2007-11-28 | 2010-11-16 | Boston Scientific Scimed, Inc. | Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment |
US7815687B2 (en) * | 2007-12-18 | 2010-10-19 | Med Institute, Inc. | Method of promoting cell proliferation and ingrowth by injury to the native tissue |
US8311610B2 (en) | 2008-01-31 | 2012-11-13 | C. R. Bard, Inc. | Biopsy tissue marker |
JP5581311B2 (en) | 2008-04-22 | 2014-08-27 | ボストン サイエンティフィック サイムド,インコーポレイテッド | MEDICAL DEVICE HAVING INORGANIC MATERIAL COATING AND MANUFACTURING METHOD THEREOF |
US8932346B2 (en) | 2008-04-24 | 2015-01-13 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
EP2285443B1 (en) | 2008-05-01 | 2016-11-23 | Bayer Intellectual Property GmbH | Catheter balloon drug adherence techniques and methods |
CN102056985B (en) | 2008-05-06 | 2014-02-19 | 梅塔玻利克斯公司 | Biodegradable polyester blends |
US7998192B2 (en) | 2008-05-09 | 2011-08-16 | Boston Scientific Scimed, Inc. | Endoprostheses |
US8236046B2 (en) | 2008-06-10 | 2012-08-07 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
US20090312832A1 (en) * | 2008-06-13 | 2009-12-17 | Cook Incorporated | Slip layer delivery catheter |
US8449603B2 (en) | 2008-06-18 | 2013-05-28 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US7951193B2 (en) | 2008-07-23 | 2011-05-31 | Boston Scientific Scimed, Inc. | Drug-eluting stent |
EP2320985B1 (en) | 2008-07-25 | 2020-11-11 | Cook Medical Technologies LLC | Balloon catheter and method for making the same |
US7985252B2 (en) | 2008-07-30 | 2011-07-26 | Boston Scientific Scimed, Inc. | Bioerodible endoprosthesis |
US9198968B2 (en) * | 2008-09-15 | 2015-12-01 | The Spectranetics Corporation | Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens |
US8128951B2 (en) | 2008-09-15 | 2012-03-06 | Cv Ingenuity Corp. | Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens |
US8114429B2 (en) | 2008-09-15 | 2012-02-14 | Cv Ingenuity Corp. | Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens |
US8257722B2 (en) | 2008-09-15 | 2012-09-04 | Cv Ingenuity Corp. | Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens |
US9327061B2 (en) | 2008-09-23 | 2016-05-03 | Senorx, Inc. | Porous bioabsorbable implant |
US8500687B2 (en) | 2008-09-25 | 2013-08-06 | Abbott Cardiovascular Systems Inc. | Stent delivery system having a fibrous matrix covering with improved stent retention |
US8049061B2 (en) | 2008-09-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery |
US8226603B2 (en) | 2008-09-25 | 2012-07-24 | Abbott Cardiovascular Systems Inc. | Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery |
US8076529B2 (en) | 2008-09-26 | 2011-12-13 | Abbott Cardiovascular Systems, Inc. | Expandable member formed of a fibrous matrix for intraluminal drug delivery |
US8382824B2 (en) | 2008-10-03 | 2013-02-26 | Boston Scientific Scimed, Inc. | Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides |
US9078992B2 (en) | 2008-10-27 | 2015-07-14 | Pursuit Vascular, Inc. | Medical device for applying antimicrobial to proximal end of catheter |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
US8551517B2 (en) * | 2008-12-16 | 2013-10-08 | Kimberly-Clark Worldwide, Inc. | Substrates providing multiple releases of active agents |
US8670818B2 (en) | 2008-12-30 | 2014-03-11 | C. R. Bard, Inc. | Marker delivery device for tissue marker placement |
KR101034654B1 (en) * | 2009-01-15 | 2011-05-16 | 성균관대학교산학협력단 | Bioactive material coating method |
EP2403546A2 (en) | 2009-03-02 | 2012-01-11 | Boston Scientific Scimed, Inc. | Self-buffering medical implants |
US8071156B2 (en) | 2009-03-04 | 2011-12-06 | Boston Scientific Scimed, Inc. | Endoprostheses |
JP2012522591A (en) * | 2009-04-02 | 2012-09-27 | クック メディカル テクノロジーズ エルエルシー | System and method for maintaining patency of a stent using a magnet |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
JP2012532670A (en) | 2009-07-10 | 2012-12-20 | ボストン サイエンティフィック サイムド,インコーポレイテッド | Use of nanocrystals for drug delivery balloons |
US20120130300A1 (en) * | 2009-07-14 | 2012-05-24 | Board Of Regents, The Univerity Of Texas System | Therapeutic Methods Using Controlled Delivery Devices Having Zero Order Kinetics |
WO2011008393A2 (en) | 2009-07-17 | 2011-01-20 | Boston Scientific Scimed, Inc. | Nucleation of drug delivery balloons to provide improved crystal size and density |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
CN102470196A (en) | 2009-08-27 | 2012-05-23 | 泰尔茂株式会社 | Medical device for drug delivery |
CZ20396U1 (en) * | 2009-10-12 | 2010-01-04 | Ella-Cs, S. R. O. | Stent |
MX2012004410A (en) | 2009-10-16 | 2012-08-23 | Hemoteq Ag | Use of compositions to coat catheter balloons and coated catheter balloons. |
US8016872B2 (en) * | 2009-12-22 | 2011-09-13 | Cook Medical Technologies Llc | Deployment and dilation with an expandable roll sock delivery system |
US20110160645A1 (en) * | 2009-12-31 | 2011-06-30 | Boston Scientific Scimed, Inc. | Cryo Activated Drug Delivery and Cutting Balloons |
US8398916B2 (en) * | 2010-03-04 | 2013-03-19 | Icon Medical Corp. | Method for forming a tubular medical device |
US8668732B2 (en) | 2010-03-23 | 2014-03-11 | Boston Scientific Scimed, Inc. | Surface treated bioerodible metal endoprostheses |
DE102010022588A1 (en) | 2010-05-27 | 2011-12-01 | Hemoteq Ag | Balloon catheter with a particle-free drug-releasing coating |
EP2593141B1 (en) | 2010-07-16 | 2018-07-04 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
US8889211B2 (en) | 2010-09-02 | 2014-11-18 | Boston Scientific Scimed, Inc. | Coating process for drug delivery balloons using heat-induced rewrap memory |
US8709034B2 (en) | 2011-05-13 | 2014-04-29 | Broncus Medical Inc. | Methods and devices for diagnosing, monitoring, or treating medical conditions through an opening through an airway wall |
WO2012158553A2 (en) | 2011-05-13 | 2012-11-22 | Broncus Technologies, Inc. | Methods and devices for excision of tissue |
WO2013007273A1 (en) | 2011-07-08 | 2013-01-17 | Cardionovum Sp.Z.O.O. | Balloon surface coating |
CN106902405B (en) | 2011-07-12 | 2020-12-11 | Icu医学有限公司 | Device for delivering antimicrobial agents into a percutaneous catheter |
WO2013022458A1 (en) | 2011-08-05 | 2013-02-14 | Boston Scientific Scimed, Inc. | Methods of converting amorphous drug substance into crystalline form |
US9056152B2 (en) | 2011-08-25 | 2015-06-16 | Boston Scientific Scimed, Inc. | Medical device with crystalline drug coating |
WO2013078235A1 (en) | 2011-11-23 | 2013-05-30 | Broncus Medical Inc | Methods and devices for diagnosing, monitoring, or treating medical conditions through an opening through an airway wall |
US8992595B2 (en) | 2012-04-04 | 2015-03-31 | Trivascular, Inc. | Durable stent graft with tapered struts and stable delivery methods and devices |
US9498363B2 (en) | 2012-04-06 | 2016-11-22 | Trivascular, Inc. | Delivery catheter for endovascular device |
US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
US9956385B2 (en) | 2012-06-28 | 2018-05-01 | The Spectranetics Corporation | Post-processing of a medical device to control morphology and mechanical properties |
US9475930B2 (en) | 2012-08-17 | 2016-10-25 | Metabolix, Inc. | Biobased rubber modifiers for polymer blends |
EP3004225A1 (en) | 2013-05-30 | 2016-04-13 | Metabolix, Inc. | Recyclate blends |
USD715942S1 (en) | 2013-09-24 | 2014-10-21 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD715442S1 (en) | 2013-09-24 | 2014-10-14 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716450S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716451S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
US10525171B2 (en) | 2014-01-24 | 2020-01-07 | The Spectranetics Corporation | Coatings for medical devices |
WO2015149029A1 (en) | 2014-03-27 | 2015-10-01 | Metabolix, Inc. | Highly filled polymer systems |
WO2015199816A1 (en) | 2014-06-24 | 2015-12-30 | Icon Medical Corp. | Improved metal alloys for medical devices |
CN104083805B (en) * | 2014-07-24 | 2015-11-18 | 吉林大学 | A kind of method preparing degradable drug-carried coat support |
JP6008213B2 (en) * | 2014-08-06 | 2016-10-19 | リューベン,アレクサンダー | Method for producing bioactive surface on endoprosthesis or balloon of balloon catheter |
EP3294404A4 (en) | 2015-05-08 | 2018-11-14 | ICU Medical, Inc. | Medical connectors configured to receive emitters of therapeutic agents |
JP2018529759A (en) | 2015-08-14 | 2018-10-11 | ザ ユニバーシティー オブ シドニー | Therapeutic connexin 45 inhibitor |
CN105597161A (en) * | 2015-12-23 | 2016-05-25 | 新乡医学院第一附属医院 | Biodegradable intravascular stent with composite coating |
US11766506B2 (en) | 2016-03-04 | 2023-09-26 | Mirus Llc | Stent device for spinal fusion |
SI3525865T1 (en) | 2016-10-14 | 2023-01-31 | Icu Medical, Inc. | Sanitizing caps for medical connectors |
US10531941B2 (en) | 2016-11-09 | 2020-01-14 | Boston Scientific Scimed, Inc. | Stent including anti-migration capabilities |
WO2018204206A2 (en) | 2017-05-01 | 2018-11-08 | Icu Medical, Inc. | Medical fluid connectors and methods for providing additives in medical fluid lines |
US11690645B2 (en) | 2017-05-03 | 2023-07-04 | Medtronic Vascular, Inc. | Tissue-removing catheter |
US10869689B2 (en) | 2017-05-03 | 2020-12-22 | Medtronic Vascular, Inc. | Tissue-removing catheter |
JP2021524841A (en) | 2018-05-24 | 2021-09-16 | セラニーズ・イーブイエイ・パフォーマンス・ポリマーズ・エルエルシー | Implantable device for sustained release of macromolecular drug compounds |
EP3801378A4 (en) | 2018-05-24 | 2022-02-23 | Celanese EVA Performance Polymers LLC | Implantable device for sustained release of a macromolecular drug compound |
US11400195B2 (en) | 2018-11-07 | 2022-08-02 | Icu Medical, Inc. | Peritoneal dialysis transfer set with antimicrobial properties |
US11517732B2 (en) | 2018-11-07 | 2022-12-06 | Icu Medical, Inc. | Syringe with antimicrobial properties |
US11534595B2 (en) | 2018-11-07 | 2022-12-27 | Icu Medical, Inc. | Device for delivering an antimicrobial composition into an infusion device |
US11541220B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Needleless connector with antimicrobial properties |
US11541221B2 (en) | 2018-11-07 | 2023-01-03 | Icu Medical, Inc. | Tubing set with antimicrobial properties |
WO2020102729A1 (en) | 2018-11-16 | 2020-05-22 | Medtronic Vascular, Inc. | Tissue-removing catheter |
JP2022513096A (en) | 2018-11-21 | 2022-02-07 | アイシーユー・メディカル・インコーポレーテッド | Antibacterial device with cap with ring and insert |
DE102019104827B4 (en) * | 2019-02-26 | 2020-12-17 | Acandis Gmbh | Intravascular functional element, system with one functional element and method |
US11819236B2 (en) | 2019-05-17 | 2023-11-21 | Medtronic Vascular, Inc. | Tissue-removing catheter |
US20220218880A1 (en) * | 2019-06-10 | 2022-07-14 | The Regents Of The University Of Michigan | Catheter insert devices |
JP2024500319A (en) | 2020-12-07 | 2024-01-09 | アイシーユー・メディカル・インコーポレーテッド | Peritoneal dialysis cap, system, and method |
KR102532990B1 (en) * | 2021-01-28 | 2023-05-15 | 경북대학교 산학협력단 | A manufacturing method for medical stent using laser |
CN113476658A (en) * | 2021-07-16 | 2021-10-08 | 北京理工大学重庆创新中心 | Bessel beam-based bone joint implant surface treatment method |
KR102665324B1 (en) * | 2022-03-03 | 2024-05-14 | 가톨릭대학교 산학협력단 | Composite material for 3d printing, manufacturing method thereof, and 3d printed stent comprising the same |
CN116585602B (en) * | 2023-07-18 | 2023-10-03 | 上海威高医疗技术发展有限公司 | Method for improving utilization rate of medicine on surface of balloon and prepared balloon |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5053048A (en) * | 1988-09-22 | 1991-10-01 | Cordis Corporation | Thromboresistant coating |
US5226260A (en) * | 1992-01-09 | 1993-07-13 | Ventritex, Inc. | Method for manufacturing implantable cardiac defibrillation leads utilizing a material removal process |
US5599352A (en) * | 1992-03-19 | 1997-02-04 | Medtronic, Inc. | Method of making a drug eluting stent |
US5464650A (en) * | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US5380299A (en) | 1993-08-30 | 1995-01-10 | Med Institute, Inc. | Thrombolytic treated intravascular medical device |
US5383299A (en) * | 1993-10-04 | 1995-01-24 | Smelker; Delmer M. | Fishing rod holders |
CA2178541C (en) * | 1995-06-07 | 2009-11-24 | Neal E. Fearnot | Implantable medical device |
US5609629A (en) * | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US6441025B2 (en) | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
EP0806212B1 (en) | 1996-05-10 | 2003-04-02 | IsoTis N.V. | Device for incorporation and release of biologically active agents |
US5951586A (en) * | 1996-05-15 | 1999-09-14 | Medtronic, Inc. | Intraluminal stent |
US6099561A (en) * | 1996-10-21 | 2000-08-08 | Inflow Dynamics, Inc. | Vascular and endoluminal stents with improved coatings |
IT1289815B1 (en) * | 1996-12-30 | 1998-10-16 | Sorin Biomedica Cardio Spa | ANGIOPLASTIC STENT AND RELATED PRODUCTION PROCESS |
US5843172A (en) * | 1997-04-15 | 1998-12-01 | Advanced Cardiovascular Systems, Inc. | Porous medicated stent |
US5934904A (en) * | 1997-10-14 | 1999-08-10 | Kreativ, Inc. | Dental instrument and processes |
US6273908B1 (en) * | 1997-10-24 | 2001-08-14 | Robert Ndondo-Lay | Stents |
AU771367B2 (en) * | 1998-08-20 | 2004-03-18 | Cook Medical Technologies Llc | Coated implantable medical device |
WO2000024437A2 (en) * | 1998-10-28 | 2000-05-04 | Ashby Scientific Ltd. | Textured and porous silicone rubber |
IL142166A0 (en) | 1998-11-06 | 2002-03-10 | Nycomed Amersham Plc | Products and methods for brachytherapy |
US6379381B1 (en) * | 1999-09-03 | 2002-04-30 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6254632B1 (en) * | 2000-09-28 | 2001-07-03 | Advanced Cardiovascular Systems, Inc. | Implantable medical device having protruding surface structures for drug delivery and cover attachment |
US6641607B1 (en) * | 2000-12-29 | 2003-11-04 | Advanced Cardiovascular Systems, Inc. | Double tube stent |
US6645135B1 (en) * | 2001-03-30 | 2003-11-11 | Advanced Cardiovascular Systems, Inc. | Intravascular catheter device and method for simultaneous local delivery of radiation and a therapeutic substance |
-
2001
- 2001-10-31 CA CA2425665A patent/CA2425665C/en not_active Expired - Lifetime
- 2001-10-31 AU AU2002239436A patent/AU2002239436B2/en not_active Expired
- 2001-10-31 AT AT01987197T patent/ATE367836T1/en not_active IP Right Cessation
- 2001-10-31 DE DE60129578T patent/DE60129578T2/en not_active Expired - Lifetime
- 2001-10-31 WO PCT/US2001/045577 patent/WO2003026718A1/en active IP Right Grant
- 2001-10-31 KR KR10-2003-7006028A patent/KR20030045847A/en not_active Application Discontinuation
- 2001-10-31 US US10/000,659 patent/US6918927B2/en not_active Expired - Lifetime
- 2001-10-31 JP JP2003530350A patent/JP4583756B2/en not_active Expired - Lifetime
- 2001-10-31 EP EP01987197A patent/EP1330273B1/en not_active Expired - Lifetime
-
2003
- 2003-08-05 HK HK03105622A patent/HK1053270A1/en not_active IP Right Cessation
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111032098A (en) * | 2017-08-01 | 2020-04-17 | 株式会社多磨生物科技 | Medical sheet |
CN111032098B (en) * | 2017-08-01 | 2022-07-26 | 株式会社多磨生物科技 | Medical sheet and method for producing same |
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