JP2006506209A - Improved endoprosthesis and method of manufacture - Google Patents

Abstract

An improved endoprosthesis and method of manufacture with a delivery shape and a deployed shape is disclosed. Some embodiments according to the invention comprise woven tubular structures and means for holding the structures in their expanded shape. In one embodiment of the invention, locking elements (12, 14) disposed on one or more fibers (15, 17) hold the endoprosthesis in its deployed shape. In an alternative embodiment, one or more shaft members can hold the endoprosthesis in its deployed shape. In still other embodiments, a chemical bond or thermocouple can hold the endoprosthesis in its deployed shape. Some embodiments according to the invention may include an erodible material.

Description

Related applications

  This application is a benefit of US Provisional Application No. 60 / 426,737, filed November 15, 2002, and US Provisional Application No. 10 / 342,622, filed January 15, 2003. Each of which is hereby incorporated by reference in its entirety.

  The present invention relates generally to medical devices and their manufacture, and more particularly to an improved endoprosthesis used to treat stenosis in a body cavity.

  Ischemic heart disease is the leading cause of death in industrialized countries. Ischemic heart disease, often resulting in myocardial infarction, is the result of coronary atherosclerosis. Atherosclerosis is a complex, chronic inflammatory disease that involves the local accumulation of lipids and inflammatory cells, the proliferation and migration of smooth muscle cells, and the synthesis of extracellular matrix. “Nature”, 362, 801-809 (1993). These complex cellular reactions form atheroma plaques consisting of lipid-rich nuclei covered by a collagen-rich fibrous cap. The thickness of this atheroma plaque varies greatly. In addition, internal bleeding and luminal thrombosis occur to varying degrees with the collapse of atheroma. This is because lipid nuclei and exposed collagen have a thrombogenic effect. “J Am Coll Cardiol.” 23, 1562-1569 (1994). Acute coronary syndromes usually occur as a result of such collapse or ulceration of so-called “fragile plaques”. “Arterioscler Thromb Vasc Biol.”, Vol. 22, No. 6, page 1002 (2002, June).

  In addition to coronary artery bypass surgery, current treatment techniques for reducing vascular occlusion include percutaneous and transluminal coronary angioplasty in which the lumen of the coronary artery is expanded by a balloon. In the United States, approximately 800,000 angioplasty operations are performed every year (“Arteriosclerosis, Thrombosis, and Vascular Biology”, Vol. 22, No. 6, p. 884 (2002). Year, June)). However, 30% to 50% of patients undergoing angioplasty will soon suffer significant arterial restenosis, ie arterial stenosis due to smooth muscle cell migration and growth.

  In response to significant arterial restenosis rates after angioplasty, percutaneously placed endoprostheses have been widely developed to maintain fluid flow through affected coronary arteries. Such endoprostheses, i.e., stents, traditionally made with metal alloys, are "advanced" in the vasculature and expanded by self-expansion or balloons placed in close proximity to one or more lesions. Equipped with possible devices. Although stents significantly increase the long-term gain of angiogenesis, 10% to 50% of patients receiving the stent still cause restenosis. ("American Journal of Cardiology", 39, 183-193 (2002)). For this reason, the number of people who make up a significant portion of the relevant patient population is continuously monitored and often receives additional treatment.

  A continuing improvement in stent technology is a stent that is easily tracked, easily observed, and rapidly deployed, with a small delivery cross-section and sufficient flexibility to cross the vascular system of the affected human body. It is directed to producing a stent that exhibits the required radial strength without sacrificing. In addition, the cellular mechanisms by which inflammatory cells accumulate and a number of therapeutic agents for the treatment of smooth muscle cell proliferation and migration represent a great prospect for a good long-term treatment of ischemic heart disease. As a result, the development of technology that combines the delivery of such therapeutic agents with the mechanical support of an endovascular prosthesis delivered in the vicinity of the disease site offers great hope for many patients with heart disease. It is.

  With the increasing understanding that ischemic heart disease is a complex chronic inflammatory process, conventional diagnostic techniques such as coronary angiography are being replaced by next-generation imaging techniques. Indeed, coronary angiography may not be useful at all to identify inflamed atheroma plaques that tend to produce clinical signs. For example, imaging based on temperature differences is being considered for use in detecting coronary artery disease. Magnetic resonance imaging (MRI) is currently attracting attention as a state-of-the-art diagnostic arterial imaging that improves the detection, diagnosis, and monitoring of vulnerable plaque formation. It is expected that tube intervention guided by MRI will follow. However, because metal causes distortion and artifacts in MR images, the use of conventional metal stents in coronary arteries, bile ducts, esophagus, ureters, and other body cavities is compatible with the use of MRI. do not do.

  As a result, there is clearly a clinical need for interventional devices that are compatible with and complementary to new imaging techniques. Further, there is a need for a device that has improved tracking performance for previously undetectable diseases in the remote region of the human body, particularly in the vasculature of the coronary arteries. Finally, there is a need for a device that has improved mechanical support and that can be quickly matched with ancillary therapeutics to reduce or eliminate the occurrence of restenosis.

  Improved endoprostheses and methods of manufacture are provided herein. An endoprosthesis according to the present invention may comprise a woven or braided substantially tubular structure, the endoprosthesis further comprising a delivery shape and a deployed shape. The endoprosthesis comprises one or more means for holding the endoprosthesis in a deployed configuration. The endoprosthesis may further be composed of an erodible material that is compatible with magnetic resonance imaging. An endoprosthesis according to the present invention may comprise a therapeutic agent or a coating comprising a therapeutic agent.

  The present invention includes, but is not limited to, an erodible material in some embodiments thereof. The term “erodible” refers to the ability of a material to maintain structural integrity over a desired period of time and then undergo a gradual number of processes, thereby causing the material to substantially lose tensile strength and mass. Point to. Examples of these processes include hydrolysis, enzymatic and non-enzymatic degradation, oxidation, and enzyme-assisted oxidation, ie bioresorption, dissolution when interacting with the physiological environment And mechanical breakdown into components that the patient's tissue can absorb, metabolize, breathe and / or excrete. The polymer chain is broken by hydrolysis and discharged from the human body through the Krebs circuit, mainly as carbon dioxide, into the urine. The terms “erodible” and “degradable” are intended here to be used interchangeably.

  The term “endoprosthesis” includes, but is not limited to, a body cavity or conduit for therapeutic treatment of the body cavity or conduit for the purpose of restoring or improving fluid flow through the body cavity or conduit. Refers to any prosthetic device disposed within.

  A “self-expanding” endoprosthesis has the ability to easily return from a reduced cross-sectional shape to a large cross-sectional shape without the restraint that holds the device in a reduced cross-sectional shape.

  The term “balloon expandable” has a reduced cross-sectional shape with a reduced cross-sectional shape and an expanded cross-sectional shape, via a radially outward force of the balloon expanded by any suitable inflation medium. Refers to a device that changes from an expanded shape to an expanded shape.

  The term “balloon assist” refers to a self-expanding device where the final deployment is facilitated by an expanded balloon.

  The term “fiber” refers to any generally elongated member made of any suitable material, whether polymer, metal, or metal alloy, natural or synthetic.

  When used in connection with fibers, the phrase “intersection point” means that one or more fiber portions intersect, overlap, wrap, pass tangentially, penetrate each other, or approach each other or actually Refers to any point that touches.

  After the operation of placing the device in the human body is completed, the device is referred to herein as “implanted” if it is left in the human body and held for any amount of time.

  As used herein, the term “braid” refers to one to several hundred longitudinal and / or transverse elongated elements ranging from 0 ° to 180 °, depending on the overall geometry and the desired dimensions. Any braid, mesh, or manufactured by any method of weaving, braiding, knitting, spiral winding, or twisting at an angle between 0 °, typically between 45 ° and 105 ° Refers to a similar woven structure.

  Unless specified, suitable attachment means include hot melt bonding, chemical bonding, adhesion, sintering, welding, or any known means in the art.

  The term “shape memory” means that a material that undergoes a structural phase transformation establishes a first shape under certain physical and / or chemical conditions and returns to an alternative shape when those conditions change. It refers to such ability. The shape memory material is not limited, but may be a metal alloy containing nickel titanium or a polymer. If the original shape of a polymer is recovered by heating to a temperature above the shape recovery temperature (defined as the soft segment transition temperature), the original shape of the polymer is less than the shape recovery temperature. The polymer is a shape memory polymer even if it is mechanically destroyed at low temperatures or the memorized shape can be recovered by applying other stimuli. Such other stimuli include, but are not limited to, pH, salinity, and hydration. Some embodiments according to the present invention include one or more polymers having a structure capable of taking a first shape and a second shape, and sufficient to be coated on at least a portion of the structure when the device is in the second shape. And a hydrophilic polymer having high rigidity. When the device is placed in an aqueous environment so that hydration of the hydrophilic polymer occurs, the polymer structure returns to the first shape.

  As used herein, the term “segment” refers to a block or sequence of polymer that forms part of a shape memory polymer. The terms hard segment and soft segment are relative terms with respect to the transition temperature of those segments. Generally speaking, hard segments have higher glass transition temperatures than soft segments, with exceptions. Natural polymer segments or polymers include, but are not limited to, proteins such as casein, gelatin, gluten, zein, modified zein, serum albumin, and collagen, and polysaccharides such as alginate, chitin, cellulose, dextran, pullulene. And polyhyaluronic acid, poly (3-hydroxyalkanoate), in particular poly (β-hydroxybutyrate), poly (3-hydroxyoctanoate) and poly (3-hydroxy fatty acid).

  Typical natural erodible polymer segments or polymers include polysaccharides such as alginate, dextran, cellulose, collagen, and chemical derivatives thereof (substitution, addition of chemical groups such as alkyl, alkylene, hydroxylation , Derivatives by oxidation and other modifications usually made by those skilled in the art), and proteins such as albumin, zein, and copolymers and mixtures thereof. These may be used alone or in combination with synthetic polymers.

  Suitable synthetic polymer blocks include polyphosphazene, poly (vinyl alcohol), polyamide, polyesteramide, poly (amino acid), synthetic poly (amino acid), polyanhydride, polycarbonate, polyacrylate, polyalkylene, polyacrylamide, polyalkylene Examples include glycols, polyalkylene oxides, polyalkylene terephthalates, polyorthoesters, polyvinyl ethers, polyvinyl esters, polyhalogenated vinyls, polyvinylpyrrolidones, polyesters, polylactides, polyglycolides, polysiloxanes, polyurethanes, and copolymers thereof.

  Examples of suitable polyacrylates include poly (methyl methacrylate), poly (ethyl methacrylate), poly (butyl methacrylate), poly (isobutyl methacrylate), poly (hexyl methacrylate), poly (isodecyl methacrylate), poly (lauryl methacrylate) , Poly (phenyl methacrylate), poly (methyl acrylate), poly (isopropyl acrylate), poly (isobutyl acrylate), and poly (octadecyl acrylate).

  Synthetically modified natural polymers include cellulose derivatives such as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitrocellulose, and chitosan. Examples of suitable cellulose derivatives include methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, cellulose acetate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, arboxymethylcellulose, cellulose triacetate, cellulose sulfate A sodium salt is mentioned. These are collectively referred to herein as “cellulose”.

  Examples of degradable synthetic polymer segments or polymers include polyhydroxy acids such as polylactide, polyglycolide and copolymers thereof, poly (ethylene terephthalate), poly (hydroxybutyric acid), poly (oxyvaleric acid), poly [lactide -Co- (ε-caprolactone)], poly [glycolide-co- (ε-caprolactone)], polycarbonate, poly (pseudo amino acid), poly (amino acid), poly (hydroxyalkanoate), polyanhydride, polyortho Examples include esters, and blends and copolymers thereof.

  For embodiments comprising shape memory polymers, the crystallinity of the polymer or polymer block is between 3% and 80%, often between 3% and 65%. The tensile modulus of the polymer at temperatures below the transition temperature is typically between 50 MPa and 2 GPa, and the tensile modulus of the polymer at temperatures above the transition temperature is typically from 1 MPa. It is between 500 MPa. In many cases, the ratio of the elastic modulus at a temperature higher and lower than the transition temperature is 20 or more.

  The melting point and glass transition temperature of the hard segment are generally at least 10 ° C, preferably 20 ° C higher than the transition temperature of the soft segment. The transition temperature of the hard segment is preferably between 60 ° C. and 270 ° C., often between 30 ° C. and 150 ° C. The weight ratio of the hard segment to the soft segment is between about 5:95 and 95: 5, often between 20:80 and 80:20. Shape memory polymers contain at least one physical crosslink (physical interaction of hard segments) or contain covalent crosslinks instead of hard segments. The shape memory polymer may have an interpenetrating or semi-interpenetrating network.

  Use polymers that can be rapidly eroded, such as poly (lactide-co-glycolide), polyanhydrides, and polyorthoesters, with carboxyl groups exposed on the outer surface as the smooth surface of the polymer is eroded You can also. Furthermore, polymers containing unstable bonds such as polyanhydrides and polyesters are well known for their reactivity in hydrolysis. The extent of these hydrolysis can generally be altered by simply changing the polymer backbone and their sequence structure.

  Examples of competing hydrophilic polymers include, but are not limited to, poly (ethylene oxide), polyvinyl pyrrolidone, polyvinyl alcohol, poly (ethylene glycol), polyacrylamide-poly (hydroxyalkyl methacrylate), poly (hydroxyethyl methacrylate), hydrophilic Include polyurethane, HYPAN, directional HYPAN, poly (hydroxyethyl acrylate), hydroxyethyl cellulose, hydroxypropyl cellulose, methoxylated pectin gel, agar, starch, modified starch, alginate, hydroxyethyl carbohydrates, and mixtures and copolymers thereof It is done.

  Hydrogels can be made from polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylates, poly (ethylene terephthalate), poly (vinyl acetate), and copolymers and blends thereof. Some polymer segments, such as acrylic acid, exhibit a rubbery elastic state only when the polymer is hydrated and a hydrogel is formed. Other polymer segments, such as methacrylic acid, are crystalline and can be melted even when the polymer is not hydrated. Any type of polymer block can be used, depending on the desired application and conditions of use.

  The curable material includes any material that can be converted from a flowable or soft material to a hard material by cross-linking, polymerization, or other suitable process. The material can be cured over time, thermally, chemically, or by exposure to radiation. For materials that are cured by exposure to radiation, many types of radiation can be used, depending on the material. Wavelengths in the spectral range of about 100-1300 nm may be used. The material must absorb light in a wavelength range that is not rapidly absorbed by tissue, blood components, physiological fluids, or water. Ultraviolet rays having a wavelength in the range of about 100 to 400 nm may be used together with visible rays, infrared rays, and heat rays. Examples of curable materials include the following materials: urethanes, polyurethane-oligomer mixtures, acrylate monomers, aliphatic urethane acrylate oligomers, acrylamides, UV curable epoxies, photopolymerized polyanhydrides, and other UV cures. Monomer and polymer. Alternatively, the curable material may be a material that can be chemically cured, such as a silicone-based compound that is vulcanized at room temperature.

  Some embodiments according to the invention include a material that is cured in a desired pattern. Such materials may be cured by any of the means described above. Furthermore, in the case of a photo-curable material, such a pattern can be formed by coating the material with a mask material using standard photoresist techniques to obtain a negative image of the desired pattern. Can do. This blocks the absorption of both direct and incident radiation in the mask area and cures the device to the desired pattern. A variety of biocompatibles for such “masking” include but are not limited to gold, magnesium, aluminum, silver, copper, platinum, inconel, chromium, titanium-indium, indium-tin-oxide. An erodible coating material can be used. Projection optical photolithography systems that use ultraviolet wavelengths of less than 240 nm in vacuum offer benefits in that they achieve smaller cross-sectional dimensions. Such systems utilizing ultraviolet wavelengths in the 193 nm or 157 nm wavelength region can improve sophisticated masking devices having smaller cross-sectional dimensions.

  Without limitation, in some embodiments according to the present invention, the surface is treated to include one or more therapeutic substances that elute from the structure of the prosthesis, either with or without erosion of the material comprising the stent. ing. Alternatively, the therapeutic agent may be incorporated within the material that makes up the endoprosthesis. According to the present invention, the surface treatment and / or incorporation thereof for providing such a therapeutic substance is one or more of a number of steps that utilize a carbon dioxide liquid, eg, carbon dioxide in a liquid or supercritical state. It can be implemented by using.

  A supercritical fluid is a substance that exceeds its critical temperature and pressure (or “critical point”). When gas is compressed, phase separation usually occurs and a separated liquid phase appears. However, all gases have a critical temperature, i.e., a temperature above which the gas cannot be liquefied by increasing pressure, and a critical pressure, i.e., the pressure required to liquefy the gas at the critical temperature. have. For example, carbon dioxide in a supercritical state exists in a form in which the liquid state and the gas state cannot be distinguished from each other. For carbon dioxide, the critical temperature is about 31 ° C. (88 ° D), and the critical pressure is about 73 atmospheres, or about 1070 psi.

  As used herein, the term “supercritical carbon dioxide” refers to carbon dioxide at a temperature above about 31 ° C. and at a pressure above about 1070 psi. Liquid carbon dioxide can be obtained at a temperature between about −15 ° C. and about −55 ° C. and at a pressure between about 77 psi and about 335 psi. One or more solvents and blends thereof may be included in the carbon dioxide, depending on the situation. Exemplary solvents include but are not limited to isopropanol tetrafluoride, chloroform, tetrahydrofuran, cyclohexane, and methylene chloride. The content of such solvents is typically less than about 20% by weight.

  In general, carbon dioxide can be used to effectively lower the glass transition temperature of the polymeric material and facilitate the penetration of the drug into the polymeric material. Such agents include, but are not limited to, hydrophobic agents, hydrophilic agents, and particulate forms of agents. For example, after production, the endoprosthesis and the hydrophobic drug may be immersed in supercritical carbon dioxide. Supercritical carbon dioxide “plasticizes” the polymer material. That is, supercritical carbon dioxide softens the polymer material at low temperatures and allows the drug to penetrate into the polymer endoprosthesis or the polymer coating of the stent at a temperature at which the drug is unlikely to be altered and / or damaged. Can be promoted.

  As another example, an endoprosthesis and a hydrophilic drug can be immersed in water and covered with a carbon dioxide “blanket”. The hydrophilic drug enters the solution in water and carbon dioxide “plasticizes” the polymer material as described above, thereby facilitating the injection of the drug into the polymer endoprosthesis or polymer coating of the endoprosthesis. To.

  As yet another example, carbon dioxide can be used to “increase adhesion”. That is, the carbon dioxide can make the polymer endoprosthesis or the polymer coating of the endoprosthesis more adhesive and facilitate the application of the drug there in a dry fine powder. In doing so, a film-forming polymer selected in view of its ability to diffuse the drug into the interior may be applied in layers over the endoprosthesis. After curing by suitable means, a thin film is formed that allows the drug to diffuse over a predetermined period of time.

  In an alternative embodiment of the present invention, at least one monomer or comonomer can be dissolved in carbon dioxide and copolymerized with a fluorine monomer. Any suitable monomer or comonomer can be used including, but not limited to, acrylate, methacrylate, acrylamide, methacrylamide, styrenic, ethylene, and vinyl ether monomers. The copolymerization of the present invention may be carried out under the same temperature and pressure as described above.

  Reduction of platelet adhesion and aggregation at the site of arterial injury, inhibition of expression of growth factors and their receptors, for the purpose of including a therapeutic substance in the material forming the endoprosthesis or the material covering the endoprosthesis according to the present invention; Expression of competitive antagonists to growth factors, blocking of receptors from transmitting to sensitive cells, and promotion of inhibitors to smooth muscle proliferation. Antiplatelet agent, anticoagulant, antitumor agent, antifibrin agent, enzyme and enzyme inhibitor, antimitotic agent, antimetabolite, anti-inflammatory agent, antithrombin agent, antiproliferative agent, antibiotics, etc. Is preferred.

  The details of the invention can be better understood from the following description of specific embodiments according to the invention. As an example, in FIG. 1, the distal end 3 that supports the endoprosthesis 10 of a standard delivery catheter 1 is shown. While the endoprosthesis according to the present invention may be self-expanding, the endoprosthesis 10 attached to the distal end 3 is balloon expandable. Thus, the endoprosthesis 10 is deployed via the delivery catheter 1 with the balloon 5 at the distal end 3. The endoprosthesis 10 can be made from any of the conventional or shape memory materials described above, including metal alloys, polymers, or other suitable materials selected in view of molecular weight, chemical composition, and other properties. It may be made to achieve a geometric shape and then processed according to any of the foregoing descriptions. Such an endoprosthesis 10 is “pleated” over the balloon 5 in a low profile delivery configuration. The endoprosthesis 10 can then advance the determined course to a lesion in the body cavity where the endoprosthesis 10 can be deployed. In order to deploy the endoprosthesis 10, the balloon 5 is inflated via an inflation medium through the catheter 1. The radially outward force that expands the balloon 5 expands the endoprosthesis 10 to its deployed shape.

  FIG. 2 shows the endoprosthesis 10 in a deployed configuration after the catheter 1 has been removed. Thus, the endoprosthesis 10 is at its deployed diameter, which depends on the size of the patient's blood vessel (not shown) and may be between 0.5 mm and 4.0 mm. The endoprosthesis 10 includes between 1 and 50 fibers 15 and 17, which may be the same type or a composite made from one or more different materials. Alternatively, the endoprosthesis 10 may include additional fibers. The fibers 15 and 17 are braided in any suitable manner as described above so as to intersect each other at one or more points and form a generally tubular structure.

  The locking element 12 projects from the fiber 15 in the first direction 20 at an angle between 1 ° and 90 °, most suitably between 10 ° and 45 °. The locking elements 12 are spaced apart from each other by a distance between 1.0 mm and 5.0 mm, often between 1.0 mm and 3.0 mm, alone, in pairs or in groups. It is possible to function without. Similarly, the locking elements 14 protrude from the fibers 17 in a second direction 21 that is orthogonal to the first direction 20 and are spaced apart from each other by a distance corresponding to the desired dimensions of the stent 10. The locking element 12 is oriented such that when the endoprosthesis 10 is subjected to an expansion action, the fibers 15 pass through the locking element 12 in the first direction 20 until the endoprosthesis 10 is expanded to the desired diameter. . Similarly, the fiber 17 passes through the locking element 14 in the second direction 21 until the stent 10 is expanded to the desired diameter. The fibers 15 and 17 cannot pass through the locking elements 14 and 12 in the opposite direction. As a result, when the stent 10 reaches the desired diameter, the locking elements 12 and 14 engage the fibers 15 and 17, respectively, where the fibers 15 and 17 intersect each other. Thereafter, the locking elements 12 and 14 prevent the fibers 15 and 17 from sliding out of each other, thereby maintaining the position of the fibers 15 and 17 relative to each other. As a result, the endoprosthesis 10 is prevented from returning to a small diameter so that the endoprosthesis 10 has a radius to increase or restore fluid flow therethrough to the vessel or vessel wall of the patient. A continuous force can be applied outward in the direction.

  FIG. 3 shows an enlarged region A of the endoprosthesis 10 of FIG. Alternative arrangements are possible, but the pair of locking elements 12 protrudes from the fiber 15 in the first direction indicated by the arrow 20 and engages the fiber 17 where the fiber 17 intersects the fiber 15; Apply force in the direction of arrow 20. Similarly, for example, a pair of locking elements 14 protrudes from the fiber 17 in the second direction 21, although it works alone instead. The locking element 14 applies a force to the fiber 17 in a second direction 21 indicated by an arrow 21 orthogonal to the direction 20. This keeps the positions of the fibers 15 and 17 relative to each other, so that the endoprosthesis 10 retains its therapeutic diameter so that fluid flow through the lumen is enhanced or restored, and the radius of the narrow vessel wall It is possible to apply an outward force.

  As shown in FIG. 4A, the fiber 15 comprises one or more locking elements 12, which may be arranged alone, in pairs, or in any number May be arranged in an alternative suitable structure. The locking element 12 may be secured to the fiber 15 by any number of suitable methods known in the art including, but not limited to, adhesive gluing, welding, melt bonding, etc., or It may be a ridge coextruded with the fiber 15. The locking element 12 may be made from the same material as the fiber 15, or may be made from a material selected from a group of materials that exhibit higher stiffness than the fiber 15. Alternatively, endoprosthesis 10 may further include one or more therapeutic agents that are eluted at that location.

  Referring to FIG. 5, another embodiment according to the present invention is disclosed. A distal end 33 of a typical delivery catheter 31 is shown. The endoprosthesis according to the present invention may alternatively be balloon expandable, but the endoprosthesis 30 attached to the distal end 33 is self-expanding. Accordingly, the endoprosthesis 30 is crimped into a low profile delivery shape for advancement within the patient's pulmonary system and is held in that low profile shape via the sheath 34. When the distal end 33 is positioned proximate to the lesion to be treated (not shown), the sheath 34 is retracted and the endoprosthesis 30 can return to its large diameter deployed configuration. The endoprosthesis 30 is made from any number of suitable shape memory materials, including the aforementioned polymer materials and metal alloys, selected in view of the desired chemical properties, molecular weight, and other characteristics, and sterilized, desired geometry It may be processed to achieve a geometric shape and in-vivo lifetime.

  FIG. 6 shows the endoprosthesis 30 in a deployed configuration. Similar to the embodiment described with respect to FIGS. 1-4, the endoprosthesis 30 is braided to form a generally tubular structure with fibers 35 and 37 intersecting at one or more intersections 39. Fibers 35 and 37, which may be of the same or composite type and made from the same or different materials, intersect each other at an angle of 25 ° to 105 °. As the endoprosthesis 30 is expanded to its desired deployed diameter, the fibers 35 and 37 are “nested” together at the intersection 39, thereby locking the endoprosthesis 30 in its deployed configuration. Fibers 35 and 37 can be nested within each other via notch 40. These notches 40 have a width between 0.25 mm and 1.0 mm and are spaced apart from each other by a distance of 1.0 mm to 5.0 mm, depending on the desired deployment dimension.

  Notch 40 is shown in more detail in FIGS. For example, FIG. 7 shows an enlarged region B of the endoprosthesis 30. Here, the fibers 35 and 37 are in a nested form. 8A and 8B show alternative examples of fibers that can be used to make an endoprosthesis according to the present invention. The fiber 35 shown alone in FIG. 8A has a notch 40. Similarly, the fiber 41 of FIG. 8B with an alternative configuration includes a notch 44. Other configurations are also suitable.

  Notches 40 and 42 are detached from fibers 35 and 37 when stent 30 is in the delivery configuration. When deployed, the stent 30 exhibits a radially outward force because the shape memory characteristics of the material used to make the endoprosthesis 30 causes the endoprosthesis 30 to return to its deployed shape. Furthermore, the fibers 35 and 37 move elastically to “nested” in the notches 40 and 42 at the intersection 39, thereby locking the stent 30 in the deployed shape more quickly, and more It withstands pressure applied from the blood vessels to return to a small diameter.

  Without limitation, the endoprosthesis 30 may be made entirely of one or multiple curable materials, or may be coated with such materials, or one or more cured at the intersection 39. May contain a sex material. In the expanded and locked position, ultraviolet light is delivered into the device and multiple intersections are “welded” simultaneously. By curing such a curable material, the stability of the function of the “nesting” of the notches 40 and 42 can be enhanced. In yet another alternative embodiment, endoprosthesis 30 is made from one or more curable materials and cured into a pattern using photolithographic techniques as described above to improve the curing of notches 40 and 42. be able to. Further, the endoprosthesis 30 may alternatively be processed to include a therapeutic agent within the material comprising the endoprosthesis 30 or the material coated on the surface using any of the techniques described above. it can.

  Still other embodiments in accordance with the present invention can be more clearly described with respect to FIGS. Similar to the embodiment according to the invention described in connection with FIGS. 1-8, an endoprosthesis 50 in its deployed configuration is shown in FIG. 9, but the endoprosthesis 50 also has a low profile delivery configuration. The endoprosthesis 50 may be a self-expanding type, a balloon expanding type, or a balloon assist type. Endoprosthesis 50 includes fibers 52 and 54 that can be made by any of a number of possible methods, using any of a number of possible materials, such as in the aforementioned fibers. These fibers 52 and 54 are woven at an angle to each other to form a generally tubular structure. The fiber 52 includes a beaded “male” element 58 and the fiber 54 includes a “female” element 56 configured to allow the male element 58 to penetrate only in one direction. When the stent 50 is expanded by appropriate means, the male element 58 can penetrate the female element 56 and cannot be pulled back in the opposite direction. This causes the fibers 52 to be “locked” to each other so that the endoprosthesis 50 is locked to its deployed shape once expanded to the desired diameter. Alternatively, the female element 56 and the male element 58 may be constructed from a curable material and / or the endoprosthesis 50 may increase the stability of the stent 50 after being cured and deployed into a pattern. it can.

  11A and 11B show an alternative example of the configuration of the present invention described in FIGS. In FIG. 11A, the male element 55 and the female element 57 before fitting are shown. The male element 55 is configured as a spine-shaped structure, and the female element 57 is configured as a cup-shaped structure. In FIG. 11B, male element 55 is moved in the direction of arrow 59 and is irreversibly received within female element 57. Male element 55 cannot be pulled back through female element 57 in a direction opposite to the direction represented by arrow 59. However, it should be emphasized that the foregoing is merely an example and that the male and female elements may be configured in any of a number of suitable configurations for irreversible coupling.

  A completely alternative embodiment will now be described. In FIG. 12, an endoprosthesis 60 is shown. The endoprosthesis 60 has a braided fiber structure similar to that of the previous embodiment. End prosthesis 60 further includes one or more shaft members 64 that extend substantially along the length of the endoprosthesis 60. In the embodiment of FIG. 12A, the endoprosthesis 60 includes three shaft members 64 that are approximately 120 ° apart from each other. The shaft member 64 may be made from any number of elastomeric or shape memory materials. The shaft member 64 may be attached to the endoprosthesis 60 in any suitable manner known in the art including, but not limited to, the use of a suitable adhesive, chemical attachment, melt bonding, or in situ curing. It is good to adhere to. FIG. 12B shows an end view of the embodiment of FIG. Examples of possible spacing of the shaft member 64 are shown.

  The shaft member 64 applies a shortening force to the endoprosthesis 60 in the direction of arrows 65 and 66. Such shortening force acts to prevent the endoprosthesis 60 from elongating and to prevent the diameter of the endoprosthesis 60 from decreasing. This causes the shaft member 64 to “lock” the endoprosthesis 60 to the desired deployment diameter. To keep the endoprosthesis 60 in a reduced cross-sectional shape, but not limited to, when the shaft member 64 and / or the endoprosthesis 60 are in a reduced cross-sectional shape, they are coated with a hydrophilic polymer. Good. When exposed to physiological fluid, such hydrophilic polymers can erode and return the shaft member 64, and thus the endoprosthesis 60, to a large cross-sectional deployed diameter.

  FIG. 13A shows an embodiment similar to that described in connection with FIGS. 12A and 12B. In FIG. 13A, the endoprosthesis 70 in the deployed configuration is shown. End prosthesis 70 includes one or more shaft members 74 secured at or near the distal end 75 of stent 70 by any suitable means. The shaft member 74 further includes a male element 76 and a female element 78 at or near the proximal end 73 of the stent 70. When the end prosthesis 70 is deployed, the shaft member 74 is “tightened” and applies a shortening force to the end prosthesis 70. The male element 76, which can have any number of suitable shapes, is irreversibly pulled through the female element 74 in the direction of arrow 77. The male element 76 cannot pass in the opposite direction. Similar to the previous embodiment, the endoprosthesis 70 and the shaft member 74 can be fabricated by any of the aforementioned steps using any of the aforementioned materials. FIG. 13B shows an end view of the embodiment described in connection with FIG. 13A.

  14A and 14B illustrate an alternative embodiment according to the present invention. The endoprosthesis 80 is similar to the embodiment described in connection with FIGS. 1-13 to the point that it comprises a braided generally tubular structure made from two or more of any number of suitable materials. Yes. In addition, after deployment, the endoprosthesis 80 includes one or more locking regions 86 at one or more intersections 84 of the fibers. Alternatively, the locking region 86 may be defined by many other configurations. In the embodiment of FIGS. 14A and 14B, the locking region 86 comprises a chemical bond between the fibers 82 and 83.

  More specifically, the endoprosthesis 80 includes alginate fibers 82 and calcium fibers 83. The calcium fibers 83 are coated with one or more of any number of suitable hydrophilic coatings 85. When the endoprosthesis 80 is placed in an aqueous environment, the hydrophilic coating 85 dissolves, exposing the calcium fibers 83 and contacting the alginate fibers 82 at one or more, typically innumerable fiber intersections 84. . When the alginate fiber 82 and the calcium fiber 83 come into contact, a chemical reaction between these materials results in a material that cures at body temperature. As a result, as shown in FIG. 14B, a locking region 86 is formed. Alternatively, the endoprosthesis 80 is made from a material that is curable by other means, including a light curable material, and optionally cured according to a desired pattern using the photolithographic techniques detailed above. You can also.

  14C-14E illustrate different embodiments according to the present invention that also include one or more locking regions at or near the fiber intersection. In the embodiment of FIG. 14C, the one or more fiber intersections 91 comprise a thermocouple 93 made of any suitable material. Once the endoprosthesis with the thermocouple 93 has reached the deployed shape, induction heating can be used to join the fibers 90 and 94 at the intersection 91, thereby locking such an endoprosthesis in the deployed shape. it can. Alternatively, radiocoupled signals can be used to heat the thermocouple 93 to weld or join the fibers at or near the intersection.

  14D-14E illustrate alternative embodiments of the endoprosthesis locking region before and after deployment. In FIG. 14D, the fiber 97 intersects the fiber 98 at an angle 99 prior to deployment. The locking element 95 is arranged at or near the intersection 96. After deployment by self-expansion or other means, the fiber 97 intersects the fiber 98 at an angle 100 and engages the locking element 95, thereby engaging the fibers 97 and 98 at an angle 100 or near. As a result, the endoprosthesis with the locking element 95 is held in the deployed configuration.

  Any of the foregoing embodiments may further comprise a therapeutic agent that is eluted alone or with endoprosthesis erosion. As a first step, when preparing any of the aforementioned endoprostheses, the appropriate polymer in the supercritical carbon dioxide solution may be mixed with the hydrophobic therapeutic agent. As a result, a hydrophobic therapeutic agent is incorporated into the polymer. Alternatively, an embodiment according to the present invention may comprise an outer layer 120 that already contains a hydrophilic therapeutic agent, as shown in FIG. As described above, after fabrication, an endoprosthesis 117 formed by any of the aforementioned materials is immersed in a polymer, water, and hydrophilic therapeutic solution and covered with a “blanket” of supercritical carbon dioxide. . Carbon dioxide makes the uptake of therapeutic agents into the polymer even more sensitive. The polymer containing the therapeutic agent forms a layer 120 on the surface of the endoprosthesis 117.

  End prosthesis 117 further includes an end cap 118 formed from a shape memory material and disposed at or near one or more ends 119. The end cap 118 applies a radially outward force that acts to hold the endoprosthesis 117 in the deployed configuration.

  While specific forms of the invention have been illustrated and described, the foregoing description is only illustrative and it will be appreciated by those skilled in the art that various modifications can be made without departing from the spirit and scope of the invention. It will be obvious.

1 is a plan view of a distal end of a conventional balloon catheter with a stent according to the present invention attached thereto. FIG. Fig. 2 shows the embodiment of Fig. 1 in a deployed configuration. A detailed area A of FIG. 2 is shown. 3 shows examples of fibers that can be used to make the embodiment of FIGS. FIG. 6 is a plan view of the distal end of a conventional delivery catheter with an alternative embodiment according to the present invention attached. Fig. 6 shows the embodiment of Fig. 5 in a deployed configuration. The detailed area | region B of FIG. 6 is shown. 2 shows examples of fibers that can be used to make embodiments according to the present invention. Fig. 4 shows another embodiment according to the invention in a deployed configuration. The detailed area C of FIG. 9 is shown. Fig. 4 shows components of an alternative embodiment according to the present invention. It is a top view of further another embodiment of the present invention in a deployment shape. FIG. 12B shows an end view of the embodiment shown in FIG. 12A. FIG. 6 is a plan view of an alternative embodiment according to the present invention. FIG. 13B is an end view of the embodiment of FIG. 13A. FIG. 3 is a plan view of an embodiment according to the present invention. Fig. 4 shows an alternative embodiment of a locking region of an endoprosthesis according to the present invention. FIG. 6 is a plan view of yet another embodiment according to the present invention in an expanded configuration.

Claims (20)

  An endoprosthesis comprising one or more fibers delineating a generally tubular structure, the endoprosthesis comprising a delivery shape and a deployed shape, the endoprosthesis comprising means for holding the endoprosthesis in the deployed shape. In addition, an endoprosthesis.   The endoprosthesis of claim 1, wherein the endoprosthesis includes one or more erodible materials.   The endoprosthesis according to claim 1, wherein the one or more fibers comprise one or more locking elements.   The one or more fibers comprise one or more intersections, and when the endoprosthesis is in the deployed shape, at one or more of the intersections, the one or more locking elements engage the one or more fibers. The endoprosthesis according to claim 3.   The end prosthesis according to claim 4, wherein the one or more locking elements comprise locking protrusions.   The end prosthesis according to claim 4, wherein the one or more locking elements comprise one or more notches.   The endoprosthesis of claim 4, wherein the one or more locking elements comprise a male element and a female element.   5. The endoprosthesis according to claim 4, wherein the one or more fibers comprise a chemical bond at the one or more intersections when the endoprosthesis is in the deployed configuration.   The endoprosthesis according to claim 1, wherein the means for holding the endoprosthesis in the deployed configuration comprises one or more shaft members that extend substantially along the length of the endoprosthesis.   The endoprosthesis of claim 9, wherein the one or more shaft members apply a longitudinal compressive force to the endoprosthesis.   The endoprosthesis according to claim 10, wherein the one or more shaft members further comprise one or more locking elements.   The end prosthesis of claim 11, wherein the endoprosthesis comprises a first end and a second end, and wherein the one or more locking elements are proximate to the first end.   The end prosthesis according to claim 4, wherein the one or more locking elements comprise one or more thermocouples.   The endoprosthesis has a first end and a second end, and the means for holding the endoprosthesis in the deployed configuration includes one or more end caps disposed proximate to the first and second ends. The endoprosthesis of claim 1, wherein the one or more end caps apply a radially outward force when the endoprosthesis is in the deployed configuration.   The endoprosthesis according to claim 1, wherein a therapeutic agent is incorporated into or on the endoprosthesis using a solvent in a supercritical state.   The endoprosthesis of claim 1, wherein the fibers comprise one or more curable materials. A method of treating stenosis of a body cavity, the method comprising:
Providing a generally tubular end prosthesis having a delivery shape and a deployed shape and formed from one or more fibers, wherein the fibers are one or more locking elements and one between the one or more fibers. Two or more intersections, and when the endoprosthesis is in the deployed configuration, the locking element engages the fiber;
Placing the endoprosthesis in a body cavity;
Deploying the endoprosthesis, thereby engaging the locking element.   18. The locking element of claim 17, wherein the locking element comprises one or more thermocouples, and the method further comprises heating one or more of the thermocouples, thereby engaging the thermocouple. Method.   A woven erodible endoprosthesis capable of withstanding 300 mm Hg in a body cavity, the endoprosthesis comprising a delivery shape and a deployed shape, the end prosthesis for locking the endoprosthesis to the deployed shape An endoprosthesis comprising means.   The means for locking the endoprosthesis in the deployed configuration includes a directional locking / engaging mechanism that includes an engagement force of less than 0.25 pounds and a locking force of greater than 1.0 pounds. 20. An endoprosthesis according to claim 19, which requires force.

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