CA2179304C - Stent for liberating drug - Google Patents
Stent for liberating drug Download PDFInfo
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- CA2179304C CA2179304C CA002179304A CA2179304A CA2179304C CA 2179304 C CA2179304 C CA 2179304C CA 002179304 A CA002179304 A CA 002179304A CA 2179304 A CA2179304 A CA 2179304A CA 2179304 C CA2179304 C CA 2179304C
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- stent
- biodegradable polymer
- drug
- fiber
- low
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
- A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
- A61F2230/0028—Shapes in the form of latin or greek characters
- A61F2230/005—Rosette-shaped, e.g. star-shaped
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
Abstract
A stent according to the present invention is adapted to be introduced into a vascular system such as blood vessels. The stent includes a stent body produced by weaving or knitting a fiber containing a drug and made of a low-melting biodegradable polymer into a tubular shape, or coating a drug-containing low-melting biodegradable polymer on a stent body. When the stent is introduced into the vascular system, the drug contained therein is dosed in a locally limited region of the vascular system. The low-melting biodegradable polymer used has a melting point of 80° C or lower and is at least one compound selected from the group consisting of poly-.epsilon.-caprolactone, poly-D, L-deca-lactone, poly-dioxane and a copolymer thereof.
Description
DESCRIPTION
STENT FOR LIBERATING DRUG
Technical Field This invention relates to a stent for liberating a drug which is introduced into a vascular system such as blood vessels, and more particularly to a stent used for a local dosage o-f the drug.
Background Art For instance, in angioplasties, vascular walls are likely to be damaged by insertion of a catheter such as a balloon catheter or an atheroma-resecting catheter thereinto so that there occurs proliferation of the tunica intima due to a healing reaction in the vascular walls, which frequently results in a so-called restenosis_ Such a restenosis is caused by a hyperplasia of smooth muscle cells and a majority of the recurrenceof the disease is ascertained by an angiography, for example, 3 months after the angioplasty operation.
The frequency of the restenosis sums to about 30 to about 40 % though it varies-depending upon facilities used in the angioplasty operation. if any restenosis does not occur 3 months :2179304
STENT FOR LIBERATING DRUG
Technical Field This invention relates to a stent for liberating a drug which is introduced into a vascular system such as blood vessels, and more particularly to a stent used for a local dosage o-f the drug.
Background Art For instance, in angioplasties, vascular walls are likely to be damaged by insertion of a catheter such as a balloon catheter or an atheroma-resecting catheter thereinto so that there occurs proliferation of the tunica intima due to a healing reaction in the vascular walls, which frequently results in a so-called restenosis_ Such a restenosis is caused by a hyperplasia of smooth muscle cells and a majority of the recurrenceof the disease is ascertained by an angiography, for example, 3 months after the angioplasty operation.
The frequency of the restenosis sums to about 30 to about 40 % though it varies-depending upon facilities used in the angioplasty operation. if any restenosis does not occur 3 months :2179304
2 after the operation, it is suggested that the restenosis is no longer caused subsequently. -Meanwhile, any method for preventing the aforementioned restenosis has not yet been established. However, attempts, which has been made for this purpose until now, includes methods in which an instrument such as a stent or an atheroma-resecting --catheter is used, or other methods to which a genetic engineering isapplied or in which drugs such as an antimetabolite, e.g.; a carcinostatic agent, a fibroblast hyperplasia-preventing agent, or the like are used.
However, in the event that the catheter, for example, the atheroma-resecting catheter is used to prevent the restenosis of blood vessels, patients suffer from a significant pain and such an operation can be repeated only in a limited manner.
In addition, introduction of the stent into a portion subjected-to the angioplasty provides some_effect to prevent obliteration of blood vessels. However, since the stent itself has no function for restricting a hyperplasia of smooth muscle cells and preventing the restenosis, the essential problem still remains unsolved. Moreover, upon the introduction of the stent into a portion subjected to the angioplasty, there is a possibility that a thrombus occurs. Under these circumstances, in the event that the stent is used, in order to prevent occurrence ofsuch a thrombus, there has been proposed a method
However, in the event that the catheter, for example, the atheroma-resecting catheter is used to prevent the restenosis of blood vessels, patients suffer from a significant pain and such an operation can be repeated only in a limited manner.
In addition, introduction of the stent into a portion subjected-to the angioplasty provides some_effect to prevent obliteration of blood vessels. However, since the stent itself has no function for restricting a hyperplasia of smooth muscle cells and preventing the restenosis, the essential problem still remains unsolved. Moreover, upon the introduction of the stent into a portion subjected to the angioplasty, there is a possibility that a thrombus occurs. Under these circumstances, in the event that the stent is used, in order to prevent occurrence ofsuch a thrombus, there has been proposed a method
3 in which dosage of an antithrombotic agent-such as dextran, aspirin, warfarin, or-the like is used.
On the other hand, it is considered that dosage of drugs capable of restricting a hyperplasia of smooth muscle cells is effective to prevent the restenosis without use of instruments such as the stent, because such dosed drugs can function so as -to prevent the sestenosis itself. However,-in this case, some problem has been posed with respect to dosage method of these drugs. - - -Similarly, in the event that the stent is used together with the antithrombotic agent to prevent the thrombus, some problem has been also posed on the dosage of the antithrombotic agent.
Inconseq~ence, a locally limited dosage is regarded as an effective method for dosage of the drugs capable of restricting a hyperplasia of smooth muscle cells or the antithrombotic agent. The locally limited dosage is carried out by a method in which a so-called dispatch catheter is used, a method in which a sweat balloon catheter is used, a method in which a double balloon catheter is used, a method in which the drugs are selectively introduced through a catheter, or the like.
The_dispatch catheter is composed of a non-porous polyurethane sheath and a spiral coil wound around the polyurethane sheath. Drugs to be dosed are supplied into the spiral coil so that the drugs can be brought into contact with -
On the other hand, it is considered that dosage of drugs capable of restricting a hyperplasia of smooth muscle cells is effective to prevent the restenosis without use of instruments such as the stent, because such dosed drugs can function so as -to prevent the sestenosis itself. However,-in this case, some problem has been posed with respect to dosage method of these drugs. - - -Similarly, in the event that the stent is used together with the antithrombotic agent to prevent the thrombus, some problem has been also posed on the dosage of the antithrombotic agent.
Inconseq~ence, a locally limited dosage is regarded as an effective method for dosage of the drugs capable of restricting a hyperplasia of smooth muscle cells or the antithrombotic agent. The locally limited dosage is carried out by a method in which a so-called dispatch catheter is used, a method in which a sweat balloon catheter is used, a method in which a double balloon catheter is used, a method in which the drugs are selectively introduced through a catheter, or the like.
The_dispatch catheter is composed of a non-porous polyurethane sheath and a spiral coil wound around the polyurethane sheath. Drugs to be dosed are supplied into the spiral coil so that the drugs can be brought into contact with -
4 walls of blood vessels. The sweat balloon catheter contains a balloon having a microporous structure. When such a sweat balloon catheter is used, drugs are gradually dosed through fine pores of the balloon irto an interior of the blood vessels. The double balloon catheter contains two balloons by which opposite ends of the portion subjected to the angioplasty are closed such that drugs are introduced through the catheter into a portion of the blood vessel between these balloons.
The.aforementioned locally limited dosage methods can advantageously increase a concentrationof the drug to be dosed, because the dosage of the drug is carried out in the locally limited region. To the contrary, since it is necessary to continuously retain the catheter in the blood vessel and thereby block a bloodstream, the locally limited dosage has such a disadvantage that it cannot be used over a long period of.time.
For instance, in the event that the sweat balloon catheter or the double ballooncatheter is used, the locally limited dosage must be carried out within several minutes. whereas, even in the event that the dispatch catheter is used or the drug is selectively introduced through the catheter, the time required for the dosage of the drug is limited to several hours. In addition, these methods have a further problem that they can be carried out only in an operating room.
Moreover, it is known that a whole-body dosage is made by a peroral, transcutaneous or transluminal dosage of drugs so that the drugs are circulated through the whole body and reaches aimed cells. The whole-body dosage has an advantage that it can be used over a long period of time.
However, in the avent of the whole-body dosage, a concentration of the drug in the blood is undesirably raised so that there is a possibility that unexpected side effects such as hepatopathy, an aspiration accident, an excess or failed dosage occur. In addition, when an antithrombotic agent is dosed by the whole-body dosage method, fine arteries and veins in a brain are damaged so that an intracerebral hemorrhage is likely to occur.
Moreover; in case that a long-term dosage is made, a large amount of the-drug is dosed so that a huge medical expense is required.
As described above, although many attempts has been made to prevent the restenosis, for example, after an angioplasty operation,-any effective method which makes the locally limited and long-term dosage of drugs possible, has not yet been found until now.
Disclosure of the Invention The present invention has been accomplished to overcome the aforementioned problems. It is therefore an object of the present invention to provide a novel stent for liberating or eluting a drug, which is capable of a locally limited and long-term dosage of the drug.
As a result of long-term intense investigations and studies made by the present inventors, the stent has been developed based on a novel concept.
That is, in accordance with the present invention, there is provided a stent which is adapted to be introduced into a vascular system such as blood vessels. The stent is composed of a stent body formed by weaving or knitting a fiber, which contains a drug and is made of a biodegradable polymer having a low-melting point at which pharmacological effects of the drug are not damaged, into a tubular body.
In this case, the amount of the drug to be added to the biodegradable polymer is determined depending upon a kind thereof. When the amount of the drug in the biodegradable polymer is too small, the drug released into the vascular system decreases so that an effect by the dosage of the drugs cannot be exhibited to a sufficient extent. On the other hand, when the amount of the drugs in the biodegradable polymer is too large, the healing process in walls of blood vessels is completely restricted so that formation of fibers or coats becomes difficult.
The kind of the drug added may be selected according to the symptom or the aimed use. Examples of the drugs may include an antimetabolite such as a carcinostatic, a fibroblast hyperplasia-preventing agent, an antithrombotic agent or the like. -, The-drugs as a solute are dissolved in the biodegradabl'e polymer as a solvent to form a solution. The solution is then hardened into a fiber from which the stent is prepared.
Alternatively, the solution may be coated on a rigid stent body having an adequate mechanical strength, for example, a metal stent body or a tubular woven or knitted stent body made of a biodegradable polymer having a high melting point.
In this case, when heated to an elevated temperature, the drug is susceptible to undesired change in its molecular structure, which leads to loss of the aimed effect or conversion to a toxic substance.
In general, the biodegradable polymer used as sutures, for example, poly-lactic acid or poly-glycolic acid, has a melting point ranging from about 2200 C to about 2400 C. Consequently, there might occur an inconvenience that the drugs added thereto is subjected to undesired chemical conversion, when heated to such an elevated temperature.
Accordingly, it is required that the biodegradable polymer has a low meting point at which the drug added can be present without loss of the pharmacological effects. For example, it is desirable that the melting point of the biodegradable polymer is 800 C or lower_ -Examples of the suitable low-melting biodegradable polymers may include poly-E-caprolactone, poly-D, L-deca-lactone, poly-r , = 2179304 di-oxanone or a copolymer of these compounds, which have a melting point of about 63 C.
However, the aforementioned low-melting biodegradable polymers cannot necessarily exhibit a sufficient mechanical strength. In consequence,-it is suitable that the fiber composed of the low melting biodegradable polymer containing the drug are woven or knitted together with those made of a high-melting biodegradable polymer to form the tubular stent body.
On the other hand, the drug added may include an antimetabolite such as.a carcinostatic, a fibroblast hyperplasia-preventing agent, or the like. For the purpose of preventing the restenosis, TORANILAST is a preferred drug.
TORANILAST is an oral anti-allergic agent and widely used as remedies for bronchial asthma, allergic rhinitis or atopic dermatitis. It has been recently found that TORANILAST has an effect of restricting a hyperplasia of smooth muscle cells. As a result, the drug is expected to show an preventive effect against the restenosis. Actually, the present inventors has confirmed the preventive effect of TORANILAST against the restenosis. -The stent according to the present invention is adapted to be introduced into a vascular system and retained in a particular region of the vascular system. At this time, the drug contained in the biodegradable polymer is released or eluted into the vascular system over 3 months in association with biodegradation of the stent. As a result, the drug contained in the biodegradable polymer is allowed to be_continuously dosed into a locally limited region of the vascular system over a long period of timewhile maintaining its concentration in a constant level.
In this case, such a locally limited dosage of the drug can be carried out without any risk of causing adverse side effects as observed in the case of the whole-body dosage. In addition, this makes it possible to dose a relatively small amount of the drugs over a long period of time.
Moreover, differing from the conventional locally limited dosage, the present invention can provide a long-term dosage without inflicting a serious pain on a patient.
Brief Description of the Drawings Fig. 1 is a perspective view schematically showing one embodiment of-a stent according to the present invention;
Fig. 2 is a perspective view schematically showing essential parts of two folded yarn composed of a fiber made of a high-melting biodegradable polymer and a fiber containing a drug and made ofa low-melting biodegradable polymer;
Fig. 3 is a perspective view schematically showing another embodiment of a stent according to the present invention;
Fig. 4 is a perspective view showing the condition in which the fiber containing the drug and made of a low-melting 1. 0 2179304 biodegradable polymer is placed around a stent body formed from a high-melting biodegradable polymer fibers and then melted so as to adhere to an outer surface thereof.
Fig. 5 is a perspective view showing a high-melting biodegradable polymer fiberwhich is knitted into a stent body of a stent according to a further embodiment of the present invention;
Fig. 6 is a perspective view showing the condition in which the fiber shown in Fig. 5 is coated with a solution composed of the low-melting biodegradable polymer containing the drug;
Fig. 7 is a perspective view showing a stent formed by knitting the high-melting biodegradable fiber which is coated with the solution composed of the low-melting biodegradable polymer containing the drug;
Fig. 8 is a perspective view showing a stent body formed from the fiber composed of the high-melting biodegradable polymer;
Fig. 9 is-a perspective view showing a still further embodiment of a stent according to the present invention in which the stent body shown in Fig. 8 is coated with the dsug-containing low-melting biodegradable polymer solution; and Fig. 10 is a perspective view showing a still further embodiment of a stent according to the present invention.
Best.Mode for Carrying Out theInvention The presernt invention will be described in more detail by way of specific examples by referring to the accompanying drawings.
Examnle 1:
The present Example shows one example of a stent which is effective for preventing a restenosis after an angioplasty operation. In Example 1, a drug used there_is TRANIRAST (N-(3, 4-dimethoxy-cinnamoyl)-anthranilic acid) represented by the following chemical formula:
O
CH30 / \ \ N
H Q
TRANIRAST is one of fibroblast hyperplasia-preventing agents. St has been reported by Tamai et al. of the present inventors that clinical experiments, in which TRANIRAST was continuously dosed for 3 months in a dosage amount of 600 mg per day (one tablet after every meal), provided such a surprising result that the restenosis rate is 15 % or lower. Consequently, the drug has been expected to provide a remarkable preventive effect against the restenosis. -TRANIRAST was added to and dissolved in a biodegradable polymer composed of poly-8-caprolactone having a melting point of about63 C to prepare a polymer solution.
The thus-prepared-polymer solution was a mixture containing TRANIRAST in an amount of 1 to 2 % by weight based on poly-8-caprolactone.
The polymer solution was then subjected to a spinning process to prepare a fiber composed of a TRANIRAST-containing poly-s-caprolactone.
Next, as shown in Fig. 1, the fiber composed of a TRANIRAST-containing poly-E-caprolactone was knitted into a tubular shape to form a stent body 10. End portions of the fiber constituting the stent body were treated to obtain a stent 11.
The thus-obtained stent 11 was produced by knitting the poly-e-caprolactone fiber 1 having a diameter of about 0.05 mm and a length of 90 crcti into a tubular shape having a diameter of 3 mm and a length of 20 mm.
Example 2:
The present Example shows another example of a stent which is produced by knitting a drug-containing low-melting biodegradable polymer fiber and a high-melting biodegradable polymer fiber together.
In Example 2, as the drug-containing biodegradable polymer fiber, there was used the TRANIRAST-containing poly-s-caprolactone fiber 1 prepared in the same manner as described in Example 1 above. The fiber was prepared in a similar manner to that of Example-1 by subjecting the polymer solution containing 1 to 2 by weight of TRANIRAST based on poly-e-caprolactone to a spinning process.
The-TRANIRAST-corntaining poly-s-caprolactone fiber 1 and the high-melting biodegradable polymer fiber 2 was formed into a two folded yarn 3 as shown in Fig. 2.'The two folded yarn 3 was knitted into a stent body 10 to obtain a stent 11.
In this case; the high-melting biodegradable polymer fiber 2 constituting the two folded yarn 3 was ptoduced by subjecting poly-lactic acid or poly-glycolic acid to a.spinning process.
In addition, the TRANIRAST-containing poly-8-caprolactone fiber 1 constituting the two folded yarn 3 was a spun yarn having a diameter of about 0.05 mm. The high-melting biodegradable polymer fiber 2 was also a spun yarn having a diameter.of about 0.05 mm. The stent body 10 was produced by knitting the two folded yarn having a length of 90 cm to a tubular body having a diameter of 3 mm and a length of 20 mm.
The size of the stent body 10 may be varied properly depending upon the vascular system towhich the stent was applied. -Alternatively, the stent 11 can-be formed by first knitting the stent body 10 and then coating the low-melting biodegradable polymer solution composed of a mixture of a solvent and a drug on the stent body 10, so that the amount of the drug contained in the stent can be controlled properly. In this case, as the low-melting biodegradable polymer solution, there is suitably used a mixture solution prepared by mixing-70 cc of acetone, 1 g of TRANIRAST and 1 g of poly-e-caprolactone together. In the event that tha solution is coated, it is desirable that the stent body 10 is subjected to a heat treatment to evaporate acetone as the solvent component.
In the foregoing, the two folded yarn 3 composed of the TRANIRAST-containing po1y-E-caprolactone fiber 1 and the high-melting biodegradable polymer fiber 2 was used to obtain the knitted stent body 10. However, a composite twisted yarn composed of plural TRANIRAST-containing po1y-E-caprolactone fibers l and plural the high-melting biodegradable polymer fibers 2 may be used for the purpose.
Exa.mple 3:
In this Example, a high-melting biodegradable polymer fiber 2 was preliminarily knitted.into a tubular shape to prepare a stent body 30. The TRANIRAST-containing poly-e-caprolactone fiber 1 as the drug-containing low-melting biodegradable polymer fiber was wound around the stent body 30 in an interlocking relation to each other so as to form a stent 21, as shown in Fig. 3. The fiber 1 was also produced by subjecting the polymer solution containing 1 to 2 % by weight of TRANIRAST based on poly-e-caprolactone to a spinning process.
In addition, the high-melting biodegradablepolymer fiber 2 used in this Example was also a poly-lactic acid fiber, a poly-glycolic acid polymer fiber or a fiber composed of a copolymer thereof.
In this Example, the stent body 30 may be also coated with a polymer solution prepared by mixing l g of TRANIRAST as a drug and 1 g of po1y-E-caprolactone.with 70 cc of acetone, so that the amount of TRANIRAST to be contained in the stent 20 can be controlled properly.
Examle 4:
In this Example, using the same procedure as described in Example 3 above, the high-melting biodegradable polymer fiber 2 was preliminarily knitted into a tubular shape to form the stent body 30. The TRANIRAST-containing poly-e-caprolactone fiber 1 as the drug-containing Iow-melting biodegradable polymer fiber was then wound around an outer circumferential surface of the stent body 30 in an interlocking relation to each other so as to form a stent 21, as shown in Fig. 3. The thus-prepared stent 20 was heated by a heating means 35 as shown in Fig. 4 to smoothen an outer surface of the stent. The heating means 35 usable here may be a blower capable of blowing hot air.
Specifically, the stent 21 was heated to a temperature at which the TRANIRAST-containing poly-E-caprolactone fiber 1 was not completely molten, namely up to the melting point of poly-s-caprolactone oY a temperature lowerthan the melting point, - =
whereby an outer peripheral surface of the TRANIRAST-containing poly-E-caprolactone fiber 1 was caused to melt so that the outer surface of the stent 21 was smoothened.
The TRANIRAST-containing poly-s-caprolactone fiber 1 may be also produced by subjecting the polymer solution containing 1 to 2 % by weight of TRANIRAST based on poly-E-caprolactone to a spinning-process: inaddition, the high-melting biodegradable polymer fiber 2 may be also a poly-lactic acid fiber, a poly-glycolic acid polymer fiber or a fiber composed of a copolymer thereof_ The smoothened outer surface of the stent 21 permits a smooth insertion of the stent into a vascular system such as blood vessels.
Examole 5-In this Example, a high-melting biodegradable pnlymer fiber 42 was coated with a solution of a drug-containing low-melting biodegradable polymer and then the coated fiber was knitted into a stent 41.
In the production of the stent 41, a biodegradable polymer material having a melting point higher than that of the drug-containing low-melting biodegradable polymer was subjected to a spinning process to obtain the biodegradable polymer fiber 42 as shown in Fig. 5. At this time, the high-melting biodegradable polymer fiber 42 used here may be fiber prepared by subjecting ~. 2179304 poly-lactic acid, poly-glycolic acid or a copolymer thereof to a spinning process.
The biodegradable polymer fiber 42 was coated with a solution 43 of drug-containing low-melting biodegradable polymer as shownnin Fig. 6. The solution 43 of drug-containing low-melting biodegradable polymer used here was a solution prepared by mixing 1 g of TRANIRAST as a drug and 1 g of po1y-E-caprolactone with 70 cc of acetone as a solvent.
Next, the high-melting biodegradable polymer fiber 42 on which the drug-containing low-melting biodegradable polymer solution 43 was coated, was knitted to form the stent 41.
Successively, the thus-knitted stent 40 was heated to evaporate acetone. The stent 40 was preferably heated to a temperature at which the drug-containing low-melting biodegradable polymer 43 was still maintained in an unmolten state. This was because melting of the drug-containing low-melting biodegradable polymer 43 was to be prevented upon heating.
Meanwhile, in the event that acetone as a solvent was already evaporated during production of the knitted stent body 40, the heating step can be omitted.
Thereafter, the stent body 40 from which acetone as a solvent was evaporated, was formed into the stent 41, as shown in Fig. 7, by treating end portions of the fiber 42 constituting the stent body 40.
~. ~ 2179304 In addition, the knitted stent body 40 may be further coated with the low-melting biodegradable polymer solution 43 prepared by mixing 1 g of TRANIRAST as a drug and 1 g of poly-E-caprolactone with-70 cc of acetone so that the amount of TRANIRAST as a drug coated on the stent body 40, can be adjusted to a proper level. in this case, it is preferred that the stent body is heated to evaporate acetone as. a solvent.
Examx~l e 6 :
In the aforementioned Examples, the high-melting biodegradable polymer fiber was first coated with the solution of the-drug-containing low-melting biodegradable polymer and then the fiber was knitted to form the stent. On the other hand, in this Example, the high-melting biodegradable polymer fiber 42 prepared by subjecting_poly-lacitc acid, poly-glycolic acid or a copolymer thereof to a spinning process was first knitted into a stent boy 50 as shown in Fig. 8. Applied over the stent body 50 was a low-melting biodegradable polymer solution 53 containing a drug as shown in Fig. 9 to form a stent 51 of this Example.
The drug-containing low-melting biodegradable polymer solution 53 applied to the stentbody 50 was a polymer solution containing 1 to 2$ by weight of TRANIRAST based onpo1y-E-caprolactone in the solution. -The application of the low-melting biodegradable polymer solution 53 to the stent body 50 may be carried out by coating the solution 53 over an outer circumferential surface thereof.
=
Alternatively, the low-melting biodegradable polymer solution 53 may be applied to the stent body 50 by immersing the stent body 50 therein.
Sxamule 7:
This Example shows a further example of a stent which is produced by coating a drug-containing biodegradable polymer solution over a stent body.
In this Example,=-=a stent 61 was produced by coating the drug-containing biodegradable polymer solution on the stent body made of metal to form a layer 62 composed of drug-containing biodegradable polymerover an outer surface of the stent body 60, as shown in Fig. 10. The solution coated contained 1 to 2 %
by weight of the drug based on poly-E-caprolactone (having a melting point of 63 C) in the solution.
The stent body 60 used above was made of a metal material having a thickness of 0.05 mm to 0.1 mm and formed into a cylindrical body having a diameter of 2.5 mm to 4 mm and a length of 15 mm to 25 mm. Examples of the metal material may include stainless steel, tantalum or the like.
The stent prepared in each of the aforementioned Examples was introduced into the blood vessel after angioplasty operation and held in place. As a result, it was confirmed that dosage of TRANIRASTwas carried out in an adequate manner for a long period of time, whereby occurrence of the restenosis was considerably reduced.
ao Industrial Applicability As is apparently understood from the aforementioned detailed description, the use of the stent according to the present invention enables a continuous, locally limited and long-term dosage of the drug.
In addition, such a dosage can-prevent occurrence of side effects so EF.at pains inflicted on patients can be minimized.
The.aforementioned locally limited dosage methods can advantageously increase a concentrationof the drug to be dosed, because the dosage of the drug is carried out in the locally limited region. To the contrary, since it is necessary to continuously retain the catheter in the blood vessel and thereby block a bloodstream, the locally limited dosage has such a disadvantage that it cannot be used over a long period of.time.
For instance, in the event that the sweat balloon catheter or the double ballooncatheter is used, the locally limited dosage must be carried out within several minutes. whereas, even in the event that the dispatch catheter is used or the drug is selectively introduced through the catheter, the time required for the dosage of the drug is limited to several hours. In addition, these methods have a further problem that they can be carried out only in an operating room.
Moreover, it is known that a whole-body dosage is made by a peroral, transcutaneous or transluminal dosage of drugs so that the drugs are circulated through the whole body and reaches aimed cells. The whole-body dosage has an advantage that it can be used over a long period of time.
However, in the avent of the whole-body dosage, a concentration of the drug in the blood is undesirably raised so that there is a possibility that unexpected side effects such as hepatopathy, an aspiration accident, an excess or failed dosage occur. In addition, when an antithrombotic agent is dosed by the whole-body dosage method, fine arteries and veins in a brain are damaged so that an intracerebral hemorrhage is likely to occur.
Moreover; in case that a long-term dosage is made, a large amount of the-drug is dosed so that a huge medical expense is required.
As described above, although many attempts has been made to prevent the restenosis, for example, after an angioplasty operation,-any effective method which makes the locally limited and long-term dosage of drugs possible, has not yet been found until now.
Disclosure of the Invention The present invention has been accomplished to overcome the aforementioned problems. It is therefore an object of the present invention to provide a novel stent for liberating or eluting a drug, which is capable of a locally limited and long-term dosage of the drug.
As a result of long-term intense investigations and studies made by the present inventors, the stent has been developed based on a novel concept.
That is, in accordance with the present invention, there is provided a stent which is adapted to be introduced into a vascular system such as blood vessels. The stent is composed of a stent body formed by weaving or knitting a fiber, which contains a drug and is made of a biodegradable polymer having a low-melting point at which pharmacological effects of the drug are not damaged, into a tubular body.
In this case, the amount of the drug to be added to the biodegradable polymer is determined depending upon a kind thereof. When the amount of the drug in the biodegradable polymer is too small, the drug released into the vascular system decreases so that an effect by the dosage of the drugs cannot be exhibited to a sufficient extent. On the other hand, when the amount of the drugs in the biodegradable polymer is too large, the healing process in walls of blood vessels is completely restricted so that formation of fibers or coats becomes difficult.
The kind of the drug added may be selected according to the symptom or the aimed use. Examples of the drugs may include an antimetabolite such as a carcinostatic, a fibroblast hyperplasia-preventing agent, an antithrombotic agent or the like. -, The-drugs as a solute are dissolved in the biodegradabl'e polymer as a solvent to form a solution. The solution is then hardened into a fiber from which the stent is prepared.
Alternatively, the solution may be coated on a rigid stent body having an adequate mechanical strength, for example, a metal stent body or a tubular woven or knitted stent body made of a biodegradable polymer having a high melting point.
In this case, when heated to an elevated temperature, the drug is susceptible to undesired change in its molecular structure, which leads to loss of the aimed effect or conversion to a toxic substance.
In general, the biodegradable polymer used as sutures, for example, poly-lactic acid or poly-glycolic acid, has a melting point ranging from about 2200 C to about 2400 C. Consequently, there might occur an inconvenience that the drugs added thereto is subjected to undesired chemical conversion, when heated to such an elevated temperature.
Accordingly, it is required that the biodegradable polymer has a low meting point at which the drug added can be present without loss of the pharmacological effects. For example, it is desirable that the melting point of the biodegradable polymer is 800 C or lower_ -Examples of the suitable low-melting biodegradable polymers may include poly-E-caprolactone, poly-D, L-deca-lactone, poly-r , = 2179304 di-oxanone or a copolymer of these compounds, which have a melting point of about 63 C.
However, the aforementioned low-melting biodegradable polymers cannot necessarily exhibit a sufficient mechanical strength. In consequence,-it is suitable that the fiber composed of the low melting biodegradable polymer containing the drug are woven or knitted together with those made of a high-melting biodegradable polymer to form the tubular stent body.
On the other hand, the drug added may include an antimetabolite such as.a carcinostatic, a fibroblast hyperplasia-preventing agent, or the like. For the purpose of preventing the restenosis, TORANILAST is a preferred drug.
TORANILAST is an oral anti-allergic agent and widely used as remedies for bronchial asthma, allergic rhinitis or atopic dermatitis. It has been recently found that TORANILAST has an effect of restricting a hyperplasia of smooth muscle cells. As a result, the drug is expected to show an preventive effect against the restenosis. Actually, the present inventors has confirmed the preventive effect of TORANILAST against the restenosis. -The stent according to the present invention is adapted to be introduced into a vascular system and retained in a particular region of the vascular system. At this time, the drug contained in the biodegradable polymer is released or eluted into the vascular system over 3 months in association with biodegradation of the stent. As a result, the drug contained in the biodegradable polymer is allowed to be_continuously dosed into a locally limited region of the vascular system over a long period of timewhile maintaining its concentration in a constant level.
In this case, such a locally limited dosage of the drug can be carried out without any risk of causing adverse side effects as observed in the case of the whole-body dosage. In addition, this makes it possible to dose a relatively small amount of the drugs over a long period of time.
Moreover, differing from the conventional locally limited dosage, the present invention can provide a long-term dosage without inflicting a serious pain on a patient.
Brief Description of the Drawings Fig. 1 is a perspective view schematically showing one embodiment of-a stent according to the present invention;
Fig. 2 is a perspective view schematically showing essential parts of two folded yarn composed of a fiber made of a high-melting biodegradable polymer and a fiber containing a drug and made ofa low-melting biodegradable polymer;
Fig. 3 is a perspective view schematically showing another embodiment of a stent according to the present invention;
Fig. 4 is a perspective view showing the condition in which the fiber containing the drug and made of a low-melting 1. 0 2179304 biodegradable polymer is placed around a stent body formed from a high-melting biodegradable polymer fibers and then melted so as to adhere to an outer surface thereof.
Fig. 5 is a perspective view showing a high-melting biodegradable polymer fiberwhich is knitted into a stent body of a stent according to a further embodiment of the present invention;
Fig. 6 is a perspective view showing the condition in which the fiber shown in Fig. 5 is coated with a solution composed of the low-melting biodegradable polymer containing the drug;
Fig. 7 is a perspective view showing a stent formed by knitting the high-melting biodegradable fiber which is coated with the solution composed of the low-melting biodegradable polymer containing the drug;
Fig. 8 is a perspective view showing a stent body formed from the fiber composed of the high-melting biodegradable polymer;
Fig. 9 is-a perspective view showing a still further embodiment of a stent according to the present invention in which the stent body shown in Fig. 8 is coated with the dsug-containing low-melting biodegradable polymer solution; and Fig. 10 is a perspective view showing a still further embodiment of a stent according to the present invention.
Best.Mode for Carrying Out theInvention The presernt invention will be described in more detail by way of specific examples by referring to the accompanying drawings.
Examnle 1:
The present Example shows one example of a stent which is effective for preventing a restenosis after an angioplasty operation. In Example 1, a drug used there_is TRANIRAST (N-(3, 4-dimethoxy-cinnamoyl)-anthranilic acid) represented by the following chemical formula:
O
CH30 / \ \ N
H Q
TRANIRAST is one of fibroblast hyperplasia-preventing agents. St has been reported by Tamai et al. of the present inventors that clinical experiments, in which TRANIRAST was continuously dosed for 3 months in a dosage amount of 600 mg per day (one tablet after every meal), provided such a surprising result that the restenosis rate is 15 % or lower. Consequently, the drug has been expected to provide a remarkable preventive effect against the restenosis. -TRANIRAST was added to and dissolved in a biodegradable polymer composed of poly-8-caprolactone having a melting point of about63 C to prepare a polymer solution.
The thus-prepared-polymer solution was a mixture containing TRANIRAST in an amount of 1 to 2 % by weight based on poly-8-caprolactone.
The polymer solution was then subjected to a spinning process to prepare a fiber composed of a TRANIRAST-containing poly-s-caprolactone.
Next, as shown in Fig. 1, the fiber composed of a TRANIRAST-containing poly-E-caprolactone was knitted into a tubular shape to form a stent body 10. End portions of the fiber constituting the stent body were treated to obtain a stent 11.
The thus-obtained stent 11 was produced by knitting the poly-e-caprolactone fiber 1 having a diameter of about 0.05 mm and a length of 90 crcti into a tubular shape having a diameter of 3 mm and a length of 20 mm.
Example 2:
The present Example shows another example of a stent which is produced by knitting a drug-containing low-melting biodegradable polymer fiber and a high-melting biodegradable polymer fiber together.
In Example 2, as the drug-containing biodegradable polymer fiber, there was used the TRANIRAST-containing poly-s-caprolactone fiber 1 prepared in the same manner as described in Example 1 above. The fiber was prepared in a similar manner to that of Example-1 by subjecting the polymer solution containing 1 to 2 by weight of TRANIRAST based on poly-e-caprolactone to a spinning process.
The-TRANIRAST-corntaining poly-s-caprolactone fiber 1 and the high-melting biodegradable polymer fiber 2 was formed into a two folded yarn 3 as shown in Fig. 2.'The two folded yarn 3 was knitted into a stent body 10 to obtain a stent 11.
In this case; the high-melting biodegradable polymer fiber 2 constituting the two folded yarn 3 was ptoduced by subjecting poly-lactic acid or poly-glycolic acid to a.spinning process.
In addition, the TRANIRAST-containing poly-8-caprolactone fiber 1 constituting the two folded yarn 3 was a spun yarn having a diameter of about 0.05 mm. The high-melting biodegradable polymer fiber 2 was also a spun yarn having a diameter.of about 0.05 mm. The stent body 10 was produced by knitting the two folded yarn having a length of 90 cm to a tubular body having a diameter of 3 mm and a length of 20 mm.
The size of the stent body 10 may be varied properly depending upon the vascular system towhich the stent was applied. -Alternatively, the stent 11 can-be formed by first knitting the stent body 10 and then coating the low-melting biodegradable polymer solution composed of a mixture of a solvent and a drug on the stent body 10, so that the amount of the drug contained in the stent can be controlled properly. In this case, as the low-melting biodegradable polymer solution, there is suitably used a mixture solution prepared by mixing-70 cc of acetone, 1 g of TRANIRAST and 1 g of poly-e-caprolactone together. In the event that tha solution is coated, it is desirable that the stent body 10 is subjected to a heat treatment to evaporate acetone as the solvent component.
In the foregoing, the two folded yarn 3 composed of the TRANIRAST-containing po1y-E-caprolactone fiber 1 and the high-melting biodegradable polymer fiber 2 was used to obtain the knitted stent body 10. However, a composite twisted yarn composed of plural TRANIRAST-containing po1y-E-caprolactone fibers l and plural the high-melting biodegradable polymer fibers 2 may be used for the purpose.
Exa.mple 3:
In this Example, a high-melting biodegradable polymer fiber 2 was preliminarily knitted.into a tubular shape to prepare a stent body 30. The TRANIRAST-containing poly-e-caprolactone fiber 1 as the drug-containing low-melting biodegradable polymer fiber was wound around the stent body 30 in an interlocking relation to each other so as to form a stent 21, as shown in Fig. 3. The fiber 1 was also produced by subjecting the polymer solution containing 1 to 2 % by weight of TRANIRAST based on poly-e-caprolactone to a spinning process.
In addition, the high-melting biodegradablepolymer fiber 2 used in this Example was also a poly-lactic acid fiber, a poly-glycolic acid polymer fiber or a fiber composed of a copolymer thereof.
In this Example, the stent body 30 may be also coated with a polymer solution prepared by mixing l g of TRANIRAST as a drug and 1 g of po1y-E-caprolactone.with 70 cc of acetone, so that the amount of TRANIRAST to be contained in the stent 20 can be controlled properly.
Examle 4:
In this Example, using the same procedure as described in Example 3 above, the high-melting biodegradable polymer fiber 2 was preliminarily knitted into a tubular shape to form the stent body 30. The TRANIRAST-containing poly-e-caprolactone fiber 1 as the drug-containing Iow-melting biodegradable polymer fiber was then wound around an outer circumferential surface of the stent body 30 in an interlocking relation to each other so as to form a stent 21, as shown in Fig. 3. The thus-prepared stent 20 was heated by a heating means 35 as shown in Fig. 4 to smoothen an outer surface of the stent. The heating means 35 usable here may be a blower capable of blowing hot air.
Specifically, the stent 21 was heated to a temperature at which the TRANIRAST-containing poly-E-caprolactone fiber 1 was not completely molten, namely up to the melting point of poly-s-caprolactone oY a temperature lowerthan the melting point, - =
whereby an outer peripheral surface of the TRANIRAST-containing poly-E-caprolactone fiber 1 was caused to melt so that the outer surface of the stent 21 was smoothened.
The TRANIRAST-containing poly-s-caprolactone fiber 1 may be also produced by subjecting the polymer solution containing 1 to 2 % by weight of TRANIRAST based on poly-E-caprolactone to a spinning-process: inaddition, the high-melting biodegradable polymer fiber 2 may be also a poly-lactic acid fiber, a poly-glycolic acid polymer fiber or a fiber composed of a copolymer thereof_ The smoothened outer surface of the stent 21 permits a smooth insertion of the stent into a vascular system such as blood vessels.
Examole 5-In this Example, a high-melting biodegradable pnlymer fiber 42 was coated with a solution of a drug-containing low-melting biodegradable polymer and then the coated fiber was knitted into a stent 41.
In the production of the stent 41, a biodegradable polymer material having a melting point higher than that of the drug-containing low-melting biodegradable polymer was subjected to a spinning process to obtain the biodegradable polymer fiber 42 as shown in Fig. 5. At this time, the high-melting biodegradable polymer fiber 42 used here may be fiber prepared by subjecting ~. 2179304 poly-lactic acid, poly-glycolic acid or a copolymer thereof to a spinning process.
The biodegradable polymer fiber 42 was coated with a solution 43 of drug-containing low-melting biodegradable polymer as shownnin Fig. 6. The solution 43 of drug-containing low-melting biodegradable polymer used here was a solution prepared by mixing 1 g of TRANIRAST as a drug and 1 g of po1y-E-caprolactone with 70 cc of acetone as a solvent.
Next, the high-melting biodegradable polymer fiber 42 on which the drug-containing low-melting biodegradable polymer solution 43 was coated, was knitted to form the stent 41.
Successively, the thus-knitted stent 40 was heated to evaporate acetone. The stent 40 was preferably heated to a temperature at which the drug-containing low-melting biodegradable polymer 43 was still maintained in an unmolten state. This was because melting of the drug-containing low-melting biodegradable polymer 43 was to be prevented upon heating.
Meanwhile, in the event that acetone as a solvent was already evaporated during production of the knitted stent body 40, the heating step can be omitted.
Thereafter, the stent body 40 from which acetone as a solvent was evaporated, was formed into the stent 41, as shown in Fig. 7, by treating end portions of the fiber 42 constituting the stent body 40.
~. ~ 2179304 In addition, the knitted stent body 40 may be further coated with the low-melting biodegradable polymer solution 43 prepared by mixing 1 g of TRANIRAST as a drug and 1 g of poly-E-caprolactone with-70 cc of acetone so that the amount of TRANIRAST as a drug coated on the stent body 40, can be adjusted to a proper level. in this case, it is preferred that the stent body is heated to evaporate acetone as. a solvent.
Examx~l e 6 :
In the aforementioned Examples, the high-melting biodegradable polymer fiber was first coated with the solution of the-drug-containing low-melting biodegradable polymer and then the fiber was knitted to form the stent. On the other hand, in this Example, the high-melting biodegradable polymer fiber 42 prepared by subjecting_poly-lacitc acid, poly-glycolic acid or a copolymer thereof to a spinning process was first knitted into a stent boy 50 as shown in Fig. 8. Applied over the stent body 50 was a low-melting biodegradable polymer solution 53 containing a drug as shown in Fig. 9 to form a stent 51 of this Example.
The drug-containing low-melting biodegradable polymer solution 53 applied to the stentbody 50 was a polymer solution containing 1 to 2$ by weight of TRANIRAST based onpo1y-E-caprolactone in the solution. -The application of the low-melting biodegradable polymer solution 53 to the stent body 50 may be carried out by coating the solution 53 over an outer circumferential surface thereof.
=
Alternatively, the low-melting biodegradable polymer solution 53 may be applied to the stent body 50 by immersing the stent body 50 therein.
Sxamule 7:
This Example shows a further example of a stent which is produced by coating a drug-containing biodegradable polymer solution over a stent body.
In this Example,=-=a stent 61 was produced by coating the drug-containing biodegradable polymer solution on the stent body made of metal to form a layer 62 composed of drug-containing biodegradable polymerover an outer surface of the stent body 60, as shown in Fig. 10. The solution coated contained 1 to 2 %
by weight of the drug based on poly-E-caprolactone (having a melting point of 63 C) in the solution.
The stent body 60 used above was made of a metal material having a thickness of 0.05 mm to 0.1 mm and formed into a cylindrical body having a diameter of 2.5 mm to 4 mm and a length of 15 mm to 25 mm. Examples of the metal material may include stainless steel, tantalum or the like.
The stent prepared in each of the aforementioned Examples was introduced into the blood vessel after angioplasty operation and held in place. As a result, it was confirmed that dosage of TRANIRASTwas carried out in an adequate manner for a long period of time, whereby occurrence of the restenosis was considerably reduced.
ao Industrial Applicability As is apparently understood from the aforementioned detailed description, the use of the stent according to the present invention enables a continuous, locally limited and long-term dosage of the drug.
In addition, such a dosage can-prevent occurrence of side effects so EF.at pains inflicted on patients can be minimized.
Claims (12)
1. A stent for preventing restenosis, comprising:
- a fiber made of a low-melting biodegradable polymer formed as a yarn having a tubular shape embodying said stent, - said low-melting biodegradable polymer comprising TRANIRAST, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of TRANIRAST and locally liberate TRANIRAST in pre-selected dosages for extended periods of time.
- a fiber made of a low-melting biodegradable polymer formed as a yarn having a tubular shape embodying said stent, - said low-melting biodegradable polymer comprising TRANIRAST, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of TRANIRAST and locally liberate TRANIRAST in pre-selected dosages for extended periods of time.
2. The stent of claim 1, wherein said yarn is formed by weaving or knitting.
3. A stent for preventing restenosis, comprising:
- a stent body ; and - a mixture made by dissolving TRANIRAST into a low-melting biodegradable polymer, said mixture being applied to coat the exterior of said stent body, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of TRANIRAST and locally elute TRANIRAST in pre-selected dosages for extended periods of time.
- a stent body ; and - a mixture made by dissolving TRANIRAST into a low-melting biodegradable polymer, said mixture being applied to coat the exterior of said stent body, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of TRANIRAST and locally elute TRANIRAST in pre-selected dosages for extended periods of time.
4. A stent for preventing restenosis by releasing a selected drug in predetermined dosages, comprising:
a composite mesh formed by knitting two fibers into a tubular shape including, a first fiber made of a low-melting biodegradable polymer containing said drug dissolved at low temperatures, a second fiber made of a high-melting biodegradable polymer having a melting point higher than that of the first fiber, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of the drug and locally liberate the drug in said predetermined dosages for extended periods of time, while preventing lamination of the two fibres.
a composite mesh formed by knitting two fibers into a tubular shape including, a first fiber made of a low-melting biodegradable polymer containing said drug dissolved at low temperatures, a second fiber made of a high-melting biodegradable polymer having a melting point higher than that of the first fiber, whereby processing temperatures never exceed 80°C to maintain unchanged pharmacological effects of the drug and locally liberate the drug in said predetermined dosages for extended periods of time, while preventing lamination of the two fibres.
5. The stent of claim 4, wherein the low-melting biodegradable polymer is heat-fused to smooth an outer surface of the stent body.
6. The stent of claim 4, wherein said second fiber woven or knitted in a tubular shape, and said first fiber being interlocked with said second fiber to form said stent,
7. The stent of claim 4, wherein the first and second fibers are formed as a two folded yarn.
8. The stent of claim 4, wherein the high-melting biodegradable polymer is a compound selected from the group consisting of poly-lactic acid, polyglycolic acid and a copolymer thereof.
9. The stent of claim 4, wherein a solution containing said low-melting biodegradable polymer and said drug is applied to coat the exterior of said second fiber.
10. The stent of claim 4, wherein said low-melting biodegradable polymer is selected from the group consisting of poly-.epsilon.-caprolactone fiber, poly-D, L-deca-lactone, polydioxane, and a copolymer thereof.
11. The stent of claim 4, wherein said drug is selcted from the group consisting of antimetabolite, a fibroblast hyperplasia-preventing agent, and antithrombotic agent.
12. The stent of any one of claims 4 to 11, wherein said drug is TRANIRAST.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JPP6-250859 | 1994-10-17 | ||
| JP25085994 | 1994-10-17 | ||
| PCT/JP1995/002129 WO1996011720A1 (en) | 1994-10-17 | 1995-10-17 | Drug-releasing stent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2179304A1 CA2179304A1 (en) | 1996-04-25 |
| CA2179304C true CA2179304C (en) | 2008-02-05 |
Family
ID=17214077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002179304A Expired - Fee Related CA2179304C (en) | 1994-10-17 | 1995-10-17 | Stent for liberating drug |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5733327A (en) |
| EP (3) | EP0761251B1 (en) |
| AT (2) | ATE434423T1 (en) |
| AU (1) | AU699821B2 (en) |
| CA (1) | CA2179304C (en) |
| DE (2) | DE69535973D1 (en) |
| ES (1) | ES2235174T3 (en) |
| WO (1) | WO1996011720A1 (en) |
Families Citing this family (197)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5366504A (en) * | 1992-05-20 | 1994-11-22 | Boston Scientific Corporation | Tubular medical prosthesis |
| DE4418336A1 (en) † | 1994-05-26 | 1995-11-30 | Angiomed Ag | Stent for widening and holding open receptacles |
| US7896914B2 (en) * | 1995-06-07 | 2011-03-01 | Cook Incorporated | Coated implantable medical device |
| US7550005B2 (en) | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
| US20070203520A1 (en) * | 1995-06-07 | 2007-08-30 | Dennis Griffin | Endovascular filter |
| US7846202B2 (en) * | 1995-06-07 | 2010-12-07 | Cook Incorporated | Coated implantable medical device |
| 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 |
| US7611533B2 (en) * | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
| US6436104B2 (en) | 1996-01-26 | 2002-08-20 | Cordis Corporation | Bifurcated axially flexible stent |
| CA2246418A1 (en) * | 1996-02-15 | 1997-08-21 | Yukiyoshi Ajisawa | Neovascularization inhibitor |
| AU2821597A (en) * | 1996-05-03 | 1997-11-26 | Emed Corporation | Combined coronary stent deployment and local delivery of an agent |
| DE69719237T2 (en) * | 1996-05-23 | 2003-11-27 | Samsung Electronics Co Ltd | Flexible, self-expandable stent and method for its manufacture |
| WO1998011847A1 (en) * | 1996-09-20 | 1998-03-26 | Houser Russell A | Radially expanding prostheses and systems for their deployment |
| US7351421B2 (en) * | 1996-11-05 | 2008-04-01 | Hsing-Wen Sung | Drug-eluting stent having collagen drug carrier chemically treated with genipin |
| TW499412B (en) | 1996-11-26 | 2002-08-21 | Dimensional Pharm Inc | Aminoguanidines and alkoxyguanidines as protease inhibitors |
| US6273913B1 (en) * | 1997-04-18 | 2001-08-14 | Cordis Corporation | Modified stent useful for delivery of drugs along stent strut |
| US6746476B1 (en) | 1997-09-22 | 2004-06-08 | Cordis Corporation | Bifurcated axially flexible stent |
| US6161399A (en) * | 1997-10-24 | 2000-12-19 | Iowa-India Investments Company Limited | Process for manufacturing a wire reinforced monolayer fabric stent |
| US5962007A (en) * | 1997-12-19 | 1999-10-05 | Indigo Medical, Inc. | Use of a multi-component coil medical construct |
| SE514944C2 (en) | 1997-12-30 | 2001-05-21 | Lars Sunnanvaeder | Apparatus for the therapeutic treatment of a blood vessel |
| US6015432A (en) * | 1998-02-25 | 2000-01-18 | Cordis Corporation | Wire reinforced vascular prosthesis |
| US6235054B1 (en) * | 1998-02-27 | 2001-05-22 | St. Jude Medical Cardiovascular Group, Inc. | Grafts with suture connectors |
| US6001117A (en) * | 1998-03-19 | 1999-12-14 | Indigo Medical, Inc. | Bellows medical construct and apparatus and method for using same |
| US7208010B2 (en) | 2000-10-16 | 2007-04-24 | Conor Medsystems, Inc. | Expandable medical device for delivery of beneficial agent |
| US6241762B1 (en) | 1998-03-30 | 2001-06-05 | Conor Medsystems, Inc. | Expandable medical device with ductile hinges |
| US6344486B1 (en) | 1998-04-03 | 2002-02-05 | 3-Dimensional Pharmaceuticals, Inc. | Benzamide and sulfonamide substituted aminoguanidines and alkoxyguanidines as protease inhibitors |
| US8029561B1 (en) | 2000-05-12 | 2011-10-04 | Cordis Corporation | Drug combination useful for prevention of restenosis |
| US20070087028A1 (en) * | 1998-04-16 | 2007-04-19 | Robert Falotico | Intraluminal devices for the prevention and treatment of vascular disease |
| JP2003529528A (en) | 1998-04-24 | 2003-10-07 | ３−ディメンショナル ファーマシューティカルズ， インコーポレイテッド | Amino acid amidinohydrazones, alkoxyguanidines, and aminoguanidines as protease inhibitors |
| AU759427B2 (en) | 1998-06-11 | 2003-04-17 | 3-Dimensional Pharmaceuticals, Inc. | Pyrazinone protease inhibitors |
| JP4889151B2 (en) * | 1998-09-08 | 2012-03-07 | 株式会社 京都医療設計 | Vascular stent |
| AU772868C (en) | 1999-02-01 | 2005-08-11 | Board Of Regents, The University Of Texas System | Woven bifurcated and trifurcated stents and methods for making the same |
| US7018401B1 (en) | 1999-02-01 | 2006-03-28 | Board Of Regents, The University Of Texas System | Woven intravascular devices and methods for making the same and apparatus for delivery of the same |
| MXPA01011956A (en) | 1999-05-27 | 2002-06-21 | Dimensional Pharm Inc | Oxazaheterocycles as protease inhibitors. |
| WO2001004117A1 (en) | 1999-07-09 | 2001-01-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl protease inhibitors and diagnostic imaging agents |
| IT1307263B1 (en) * | 1999-08-05 | 2001-10-30 | Sorin Biomedica Cardio Spa | ANGIOPLASTIC STENT WITH RESTENOSIS ANTAGONIST ACTION, RELATED KIT AND COMPONENTS. |
| DE29915724U1 (en) | 1999-09-07 | 1999-12-23 | Angiomed Ag | Stent delivery system |
| DE69934990T2 (en) | 1999-11-23 | 2007-11-15 | Sorin Biomedica Cardio S.R.L., Saluggia | Method of transferring radioactive substances to stents in angioplasty and kit |
| US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
| US8460367B2 (en) | 2000-03-15 | 2013-06-11 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
| US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
| US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
| US20030135268A1 (en) * | 2000-04-11 | 2003-07-17 | Ashvin Desai | Secure stent for maintaining a lumenal opening |
| US7867186B2 (en) * | 2002-04-08 | 2011-01-11 | Glaukos Corporation | Devices and methods for treatment of ocular disorders |
| US20040243097A1 (en) * | 2000-05-12 | 2004-12-02 | Robert Falotico | Antiproliferative drug and delivery device |
| US6776796B2 (en) | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
| US8236048B2 (en) | 2000-05-12 | 2012-08-07 | Cordis Corporation | Drug/drug delivery systems for the prevention and treatment of vascular disease |
| US6476016B2 (en) | 2000-07-17 | 2002-11-05 | 3-Dimensional Pharmaceuticals, Inc. | Cyclic oxyguanidine pyrazinones as protease inhibitors |
| HUP0300810A2 (en) | 2000-07-20 | 2003-08-28 | M.G.V.S. Ltd. | Artifical vascular grafts, and methods of producing and using same |
| US7175658B1 (en) * | 2000-07-20 | 2007-02-13 | Multi-Gene Vascular Systems Ltd. | Artificial vascular grafts, their construction and use |
| US6569191B1 (en) * | 2000-07-27 | 2003-05-27 | Bionx Implants, Inc. | Self-expanding stent with enhanced radial expansion and shape memory |
| EP1307432A1 (en) | 2000-08-04 | 2003-05-07 | 3-Dimensional Pharmaceuticals, Inc. | Cyclic oxyguanidine protease inhibitors |
| US7261735B2 (en) * | 2001-05-07 | 2007-08-28 | Cordis Corporation | Local drug delivery devices and methods for maintaining the drug coatings thereon |
| US20020051730A1 (en) * | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
| US20020111590A1 (en) * | 2000-09-29 | 2002-08-15 | Davila Luis A. | Medical devices, drug coatings and methods for maintaining the drug coatings thereon |
| DE60124285T3 (en) | 2000-09-29 | 2011-03-17 | Cordis Corp., Miami Lakes | COATED MEDICAL EQUIPMENT |
| AU9463401A (en) * | 2000-10-16 | 2002-04-29 | Conor Medsystems Inc | Expandable medical device for delivery of beneficial agent |
| US7803149B2 (en) | 2002-07-12 | 2010-09-28 | Cook Incorporated | Coated medical device |
| CN1404405A (en) * | 2000-11-30 | 2003-03-19 | 株式会社伊垣医疗设计 | Stent for blood vessel and material for stent for blood vessel |
| WO2002055136A2 (en) * | 2000-12-01 | 2002-07-18 | Nephros Therapeutics Inc | Intrasvascular drug delivery device and use therefor |
| US20020084178A1 (en) * | 2000-12-19 | 2002-07-04 | Nicast Corporation Ltd. | Method and apparatus for manufacturing polymer fiber shells via electrospinning |
| US20070031607A1 (en) * | 2000-12-19 | 2007-02-08 | Alexander Dubson | Method and apparatus for coating medical implants |
| US20040030377A1 (en) * | 2001-10-19 | 2004-02-12 | Alexander Dubson | Medicated polymer-coated stent assembly |
| US7244272B2 (en) | 2000-12-19 | 2007-07-17 | Nicast Ltd. | Vascular prosthesis and method for production thereof |
| US8632845B2 (en) * | 2000-12-28 | 2014-01-21 | Abbott Cardiovascular Systems Inc. | Method of drying bioabsorbable coating over stents |
| US6641607B1 (en) | 2000-12-29 | 2003-11-04 | Advanced Cardiovascular Systems, Inc. | Double tube stent |
| US8277868B2 (en) * | 2001-01-05 | 2012-10-02 | Abbott Cardiovascular Systems Inc. | Balloon catheter for delivering therapeutic agents |
| US6544223B1 (en) * | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Balloon catheter for delivering therapeutic agents |
| WO2002072167A1 (en) * | 2001-03-13 | 2002-09-19 | Implant Sciences Corporation. | Drug eluting encapsulated stent |
| ATE473082T1 (en) * | 2001-03-20 | 2010-07-15 | Nicast Ltd | PORTABLE ELECTROSPINNER DEVICE |
| DE10115740A1 (en) * | 2001-03-26 | 2002-10-02 | Ulrich Speck | Preparation for restenosis prophylaxis |
| EP1372531A2 (en) * | 2001-03-30 | 2004-01-02 | Terumo Kabushiki Kaisha | Stent cover and stent |
| US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
| US8182527B2 (en) * | 2001-05-07 | 2012-05-22 | Cordis Corporation | Heparin barrier coating for controlled drug release |
| US7128755B2 (en) * | 2001-06-01 | 2006-10-31 | Texas Stent Technologies, Inc. | Expandable biodegradable polymeric stents for combined mechanical support and pharmacological or radiation therapy |
| US7842083B2 (en) | 2001-08-20 | 2010-11-30 | Innovational Holdings, Llc. | Expandable medical device with improved spatial distribution |
| US7195640B2 (en) * | 2001-09-25 | 2007-03-27 | Cordis Corporation | Coated medical devices for the treatment of vulnerable plaque |
| US7108701B2 (en) * | 2001-09-28 | 2006-09-19 | Ethicon, Inc. | Drug releasing anastomosis devices and methods for treating anastomotic sites |
| US20030065345A1 (en) * | 2001-09-28 | 2003-04-03 | Kevin Weadock | Anastomosis devices and methods for treating anastomotic sites |
| US20030065382A1 (en) * | 2001-10-02 | 2003-04-03 | Fischell Robert E. | Means and method for the treatment of coronary artery obstructions |
| US20030077310A1 (en) | 2001-10-22 | 2003-04-24 | Chandrashekhar Pathak | Stent coatings containing HMG-CoA reductase inhibitors |
| US20030077279A1 (en) * | 2001-10-24 | 2003-04-24 | Cedars-Sinai Medical Center | Methods for treating vascular disease by inhibiting toll-like receptor-4 |
| US7682387B2 (en) | 2002-04-24 | 2010-03-23 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| US20030088307A1 (en) * | 2001-11-05 | 2003-05-08 | Shulze John E. | Potent coatings for stents |
| US6939376B2 (en) | 2001-11-05 | 2005-09-06 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| US20030114919A1 (en) * | 2001-12-10 | 2003-06-19 | Mcquiston Jesse | Polymeric stent with metallic rings |
| AU2002366331A1 (en) * | 2001-12-17 | 2003-06-30 | Cedars-Sinai Medical Center | Treating vascular disease by inhibiting myeloid differentiation factor 88 |
| US7008397B2 (en) | 2002-02-13 | 2006-03-07 | Percardia, Inc. | Cardiac implant and methods |
| US7918883B2 (en) * | 2002-02-25 | 2011-04-05 | Boston Scientific Scimed, Inc. | Non-invasive heating of implanted vascular treatment device |
| US20040024450A1 (en) * | 2002-04-24 | 2004-02-05 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| US20050019404A1 (en) * | 2003-06-30 | 2005-01-27 | Hsing-Wen Sung | Drug-eluting biodegradable stent |
| US20050163821A1 (en) * | 2002-08-02 | 2005-07-28 | Hsing-Wen Sung | Drug-eluting Biodegradable Stent and Delivery Means |
| US7011676B2 (en) | 2002-09-05 | 2006-03-14 | Scimed Life Systems, Inc. | Flat knitted stent and method of making the same |
| DE10244847A1 (en) | 2002-09-20 | 2004-04-01 | Ulrich Prof. Dr. Speck | Medical device for drug delivery |
| US20040127886A1 (en) * | 2002-09-23 | 2004-07-01 | Triton Biosystems, Inc. | Stent and method for drug delivery from stents |
| WO2004028615A1 (en) | 2002-09-25 | 2004-04-08 | Kabushikikaisha Igaki Iryo Sekkei | Thread for vascular stent and vascular stent using the thread |
| US20040098106A1 (en) * | 2002-11-14 | 2004-05-20 | Williams Michael S. | Intraluminal prostheses and carbon dioxide-assisted methods of impregnating same with pharmacological agents |
| US6887266B2 (en) | 2002-11-14 | 2005-05-03 | Synecor, Llc | Endoprostheses and methods of manufacture |
| US20040098090A1 (en) * | 2002-11-14 | 2004-05-20 | Williams Michael S. | Polymeric endoprosthesis and method of manufacture |
| US7285287B2 (en) * | 2002-11-14 | 2007-10-23 | Synecor, Llc | Carbon dioxide-assisted methods of providing biocompatible intraluminal prostheses |
| US6932930B2 (en) * | 2003-03-10 | 2005-08-23 | Synecor, Llc | Intraluminal prostheses having polymeric material with selectively modified crystallinity and methods of making same |
| US7544192B2 (en) | 2003-03-14 | 2009-06-09 | Sinexus, Inc. | Sinus delivery of sustained release therapeutics |
| GB0306176D0 (en) | 2003-03-18 | 2003-04-23 | Imp College Innovations Ltd | Tubing |
| DE602004023700D1 (en) * | 2003-03-18 | 2009-12-03 | Veryan Medical Ltd | SPIRAL STONE |
| US8109987B2 (en) | 2003-04-14 | 2012-02-07 | Tryton Medical, Inc. | Method of treating a lumenal bifurcation |
| US8057537B2 (en) * | 2003-04-28 | 2011-11-15 | Kips Bay Medical, Inc. | Compliant venous graft |
| US20050131520A1 (en) * | 2003-04-28 | 2005-06-16 | Zilla Peter P. | Compliant blood vessel graft |
| US7998188B2 (en) | 2003-04-28 | 2011-08-16 | Kips Bay Medical, Inc. | Compliant blood vessel graft |
| US7318944B2 (en) | 2003-08-07 | 2008-01-15 | Medtronic Vascular, Inc. | Extrusion process for coating stents |
| US20050043786A1 (en) * | 2003-08-18 | 2005-02-24 | Medtronic Ave, Inc. | Methods and apparatus for treatment of aneurysmal tissue |
| US7198675B2 (en) | 2003-09-30 | 2007-04-03 | Advanced Cardiovascular Systems | Stent mandrel fixture and method for selectively coating surfaces of a stent |
| DE10351220A1 (en) * | 2003-10-28 | 2005-06-02 | Deutsche Institute für Textil- und Faserforschung Stuttgart - Stiftung des öffentlichen Rechts | Tubular implant |
| EP1699527A1 (en) | 2004-01-02 | 2006-09-13 | Advanced Cardiovascular Systems, Inc. | High-density lipoprotein coated medical devices |
| US20080200975A1 (en) * | 2004-01-06 | 2008-08-21 | Nicast Ltd. | Vascular Prosthesis with Anastomotic Member |
| WO2005106866A1 (en) * | 2004-04-27 | 2005-11-10 | Konica Minolta Opto, Inc. | Objective lens and optical pickup |
| US20050265960A1 (en) * | 2004-05-26 | 2005-12-01 | Pacetti Stephen D | Polymers containing poly(ester amides) and agents for use with medical articles and methods of fabricating the same |
| WO2005122953A2 (en) * | 2004-05-11 | 2005-12-29 | Oregon Health And Science University | Interfacial stent and method of maintaining patency of surgical fenestrations |
| US8617234B2 (en) | 2004-05-25 | 2013-12-31 | Covidien Lp | Flexible vascular occluding device |
| US8628564B2 (en) | 2004-05-25 | 2014-01-14 | Covidien Lp | Methods and apparatus for luminal stenting |
| US8267985B2 (en) | 2005-05-25 | 2012-09-18 | Tyco Healthcare Group Lp | System and method for delivering and deploying an occluding device within a vessel |
| JP2008502378A (en) | 2004-05-25 | 2008-01-31 | チェストナット メディカル テクノロジーズ インコーポレイテッド | Flexible vascular closure device |
| US20060206200A1 (en) | 2004-05-25 | 2006-09-14 | Chestnut Medical Technologies, Inc. | Flexible vascular occluding device |
| WO2010120926A1 (en) | 2004-05-25 | 2010-10-21 | Chestnut Medical Technologies, Inc. | Vascular stenting for aneurysms |
| EP1604697A1 (en) * | 2004-06-09 | 2005-12-14 | J.A.C.C. GmbH | Implantable device |
| EP1627722A1 (en) * | 2004-08-16 | 2006-02-22 | Medtronic Vascular, Inc. | Extrusion process for coating stents, such a coated stent and a system for treating a vascular condition |
| US7648727B2 (en) * | 2004-08-26 | 2010-01-19 | Advanced Cardiovascular Systems, Inc. | Methods for manufacturing a coated stent-balloon assembly |
| US7901451B2 (en) | 2004-09-24 | 2011-03-08 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| WO2006063430A1 (en) * | 2004-12-16 | 2006-06-22 | Miv Therapeutics Inc. | Multi-layer drug delivery device and method of manufacturing same |
| US7972354B2 (en) | 2005-01-25 | 2011-07-05 | Tyco Healthcare Group Lp | Method and apparatus for impeding migration of an implanted occlusive structure |
| US20100331947A1 (en) * | 2005-02-17 | 2010-12-30 | Alon Shalev | Inflatable Medical Device |
| RU2007140909A (en) | 2005-04-04 | 2009-05-20 | Синексус, Инк. (Us) | DEVICE AND METHODS FOR TREATING DISEASES OF THE NANOLAIN SINUS |
| AU2005332044B2 (en) | 2005-05-25 | 2012-01-19 | Covidien Lp | System and method for delivering and deploying and occluding device within a vessel |
| US8273101B2 (en) | 2005-05-25 | 2012-09-25 | Tyco Healthcare Group Lp | System and method for delivering and deploying an occluding device within a vessel |
| US20060275341A1 (en) * | 2005-06-02 | 2006-12-07 | Miv Therapeutics Inc. | Thin foam coating comprising discrete, closed-cell capsules |
| US7867547B2 (en) | 2005-12-19 | 2011-01-11 | Advanced Cardiovascular Systems, Inc. | Selectively coating luminal surfaces of stents |
| WO2007088418A1 (en) | 2006-01-31 | 2007-08-09 | Multi Gene Vascular Systems, Inc. | Drug-eluting intravascular prostheses and methods of use |
| WO2007092735A2 (en) | 2006-02-02 | 2007-08-16 | Innovative Bio Therapies | An extracorporeal cell-based therapeutic device and delivery system |
| WO2007100556A1 (en) | 2006-02-22 | 2007-09-07 | Ev3 Inc. | Embolic protection systems having radiopaque filter mesh |
| CA2645357C (en) * | 2006-04-12 | 2016-02-16 | Arterial Remodeling Technologies, S.A. | Methods of polymeric stent surface smoothing and resurfacing to reduce biologically active sites |
| CN101437471B (en) * | 2006-04-12 | 2011-08-31 | 动脉再造技术股份有限公司 | Methods of smoothing and resurfacing polymeric stent surface to reduce biologically active sites |
| US9017361B2 (en) | 2006-04-20 | 2015-04-28 | Covidien Lp | Occlusive implant and methods for hollow anatomical structure |
| US20070254003A1 (en) * | 2006-05-01 | 2007-11-01 | Pu Zhou | Non-sticky coatings with therapeutic agents for medical devices |
| US8003156B2 (en) | 2006-05-04 | 2011-08-23 | Advanced Cardiovascular Systems, Inc. | Rotatable support elements for stents |
| US8603530B2 (en) | 2006-06-14 | 2013-12-10 | Abbott Cardiovascular Systems Inc. | Nanoshell therapy |
| US8048448B2 (en) | 2006-06-15 | 2011-11-01 | Abbott Cardiovascular Systems Inc. | Nanoshells for drug delivery |
| US8017237B2 (en) | 2006-06-23 | 2011-09-13 | Abbott Cardiovascular Systems, Inc. | Nanoshells on polymers |
| US8535707B2 (en) | 2006-07-10 | 2013-09-17 | Intersect Ent, Inc. | Devices and methods for delivering active agents to the osteomeatal complex |
| US20080097591A1 (en) | 2006-10-20 | 2008-04-24 | Biosensors International Group | Drug-delivery endovascular stent and method of use |
| US8067055B2 (en) * | 2006-10-20 | 2011-11-29 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method of use |
| EP3329882B1 (en) | 2006-10-22 | 2023-09-20 | IDEV Technologies, INC. | Methods for securing strand ends and the resulting devices |
| MX2009004292A (en) | 2006-10-22 | 2009-08-12 | Idev Technologies Inc | Devices and methods for stent advancement. |
| US20080103584A1 (en) * | 2006-10-25 | 2008-05-01 | Biosensors International Group | Temporal Intraluminal Stent, Methods of Making and Using |
| EP2125066A2 (en) * | 2006-12-20 | 2009-12-02 | Boston Scientific Limited | Stent with a coating for delivering a therapeutic agent |
| US8177834B2 (en) * | 2007-03-12 | 2012-05-15 | Cook Medical Technologies Llc | Woven fabric with shape memory element strands |
| US20080243241A1 (en) | 2007-03-28 | 2008-10-02 | Zhao Jonathon Z | Short term sustained drug-delivery system for implantable medical devices and method of making the same |
| US8048441B2 (en) | 2007-06-25 | 2011-11-01 | Abbott Cardiovascular Systems, Inc. | Nanobead releasing medical devices |
| US8303640B2 (en) | 2007-07-30 | 2012-11-06 | Audubon Technologies, Llc | Device for maintaining patent paranasal sinus ostia |
| EP2195071A1 (en) * | 2007-09-06 | 2010-06-16 | Boston Scientific Scimed, Inc. | Methods and devices for local therapeutic agent delivery to heart valves |
| KR100930167B1 (en) * | 2007-09-19 | 2009-12-07 | 삼성전기주식회사 | Ultra wide angle optical system |
| WO2009041691A1 (en) * | 2007-09-28 | 2009-04-02 | Terumo Kabushiki Kaisha | In-vivo indwelling matter |
| US8661630B2 (en) | 2008-05-21 | 2014-03-04 | Abbott Cardiovascular Systems Inc. | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
| CZ303081B6 (en) * | 2007-12-13 | 2012-03-21 | Ella-Cs, S. R. O. | Process for producing self-expansion biologically degradable stent |
| WO2009079418A2 (en) | 2007-12-18 | 2009-06-25 | Sinexus, Inc. | Self-expanding devices and methods therefor |
| US20090171451A1 (en) * | 2007-12-27 | 2009-07-02 | Cook Incorporated | Implantable device having composite weave |
| US8187316B2 (en) | 2007-12-27 | 2012-05-29 | Cook Medical Technologies Llc | Implantable graft device having treated yarn and method for making same |
| US8834552B2 (en) * | 2007-12-27 | 2014-09-16 | Cook Medical Technologies Llc | Stent graft having floating yarns |
| US9675482B2 (en) | 2008-05-13 | 2017-06-13 | Covidien Lp | Braid implant delivery systems |
| WO2010071692A2 (en) * | 2008-06-18 | 2010-06-24 | Innovative Biotherapies, Inc. | Methods for enhanced propagation of cells |
| CA2732355A1 (en) | 2008-08-01 | 2010-02-04 | Intersect Ent, Inc. | Methods and devices for crimping self-expanding devices |
| WO2010033294A1 (en) | 2008-09-22 | 2010-03-25 | Cedars-Sinai Medical Center | Short-form human md-2 as a negative regulator of toll-like receptor 4 signaling |
| US9512196B2 (en) | 2008-09-22 | 2016-12-06 | Cedars-Sinai Medical Center | Short-form human MD-2 as a negative regulator of toll-like receptor 4 signaling |
| US9597214B2 (en) * | 2008-10-10 | 2017-03-21 | Kevin Heraty | Medical device |
| US20100292641A1 (en) * | 2009-05-15 | 2010-11-18 | Bandula Wijay | Targeted drug delivery device and method |
| US10357640B2 (en) | 2009-05-15 | 2019-07-23 | Intersect Ent, Inc. | Expandable devices and methods for treating a nasal or sinus condition |
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| US8382818B2 (en) | 2009-07-02 | 2013-02-26 | Tryton Medical, Inc. | Ostium support for treating vascular bifurcations |
| WO2011115882A1 (en) * | 2010-03-15 | 2011-09-22 | Boston Scientific Scimed, Inc. | Drug eluting stents and methods of making the same |
| US9023095B2 (en) | 2010-05-27 | 2015-05-05 | Idev Technologies, Inc. | Stent delivery system with pusher assembly |
| US8945207B2 (en) * | 2010-12-20 | 2015-02-03 | Graftcraft I Göteborg Ab | Removable stent and method of production |
| US10285798B2 (en) | 2011-06-03 | 2019-05-14 | Merit Medical Systems, Inc. | Esophageal stent |
| US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
| EP2747800A1 (en) | 2011-08-26 | 2014-07-02 | Ella-CS, s.r.o. | Self-expandable biodegradable stent made of clad radiopaque fibers covered with biodegradable elastic foil and therapeutic agent and method of preparation thereof |
| US9155647B2 (en) | 2012-07-18 | 2015-10-13 | Covidien Lp | Methods and apparatus for luminal stenting |
| US9114001B2 (en) | 2012-10-30 | 2015-08-25 | Covidien Lp | Systems for attaining a predetermined porosity of a vascular device |
| US9452070B2 (en) | 2012-10-31 | 2016-09-27 | Covidien Lp | Methods and systems for increasing a density of a region of a vascular device |
| US9943427B2 (en) | 2012-11-06 | 2018-04-17 | Covidien Lp | Shaped occluding devices and methods of using the same |
| US9157174B2 (en) | 2013-02-05 | 2015-10-13 | Covidien Lp | Vascular device for aneurysm treatment and providing blood flow into a perforator vessel |
| US10406332B2 (en) | 2013-03-14 | 2019-09-10 | Intersect Ent, Inc. | Systems, devices, and method for treating a sinus condition |
| CN104936557A (en) * | 2013-03-15 | 2015-09-23 | 美国医疗设备有限公司 | Esophageal stent |
| EP2994175A1 (en) | 2014-02-04 | 2016-03-16 | Abbott Cardiovascular Systems, Inc. | Drug delivery scaffold or stent with a novolimus and lactide based coating such that novolimus has a minimum amount of bonding to the coating |
| WO2015184173A1 (en) | 2014-05-29 | 2015-12-03 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| DE102015104884A1 (en) * | 2015-03-30 | 2016-10-06 | Serag-Wiessner Gmbh & Co. Kg | Textile implant |
| WO2017040853A1 (en) | 2015-09-02 | 2017-03-09 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
| US11564833B2 (en) | 2015-09-25 | 2023-01-31 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
| WO2017184881A1 (en) | 2016-04-20 | 2017-10-26 | Harold Alexander Heitzmann | Bioresorbable ocular drug delivery device |
| ES2665844A1 (en) * | 2016-10-27 | 2018-04-27 | Javier SANCHEZ ABUIN | Flexible resorbable coated stent (Machine-translation by Google Translate, not legally binding) |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4548764A (en) * | 1983-02-23 | 1985-10-22 | International Flavors & Fragrances Inc. | Insect repellent, pheremonal, animal repellent, diagnostic or aroma enhancing compositions containing poly(epsilon caprolactone) having embedded therein functional substances |
| FR2556172B1 (en) * | 1983-12-12 | 1986-09-05 | Interox | COATED SEEDS AND PROCESS FOR OBTAINING THEM |
| US5019096A (en) * | 1988-02-11 | 1991-05-28 | Trustees Of Columbia University In The City Of New York | Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same |
| US5545208A (en) * | 1990-02-28 | 1996-08-13 | Medtronic, Inc. | Intralumenal drug eluting prosthesis |
| AU650700B2 (en) * | 1991-03-08 | 1994-06-30 | Keiji Igaki | Luminal stent, holding structure therefor and device for attaching luminal stent |
| US5464450A (en) * | 1991-10-04 | 1995-11-07 | Scimed Lifesystems Inc. | Biodegradable drug delivery vascular stent |
| WO1993006792A1 (en) * | 1991-10-04 | 1993-04-15 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
| US5366504A (en) * | 1992-05-20 | 1994-11-22 | Boston Scientific Corporation | Tubular medical prosthesis |
| CA2087132A1 (en) * | 1992-01-31 | 1993-08-01 | Michael S. Williams | Stent capable of attachment within a body lumen |
| EP0566245B1 (en) * | 1992-03-19 | 1999-10-06 | Medtronic, Inc. | Intraluminal stent |
| EP0604022A1 (en) * | 1992-12-22 | 1994-06-29 | Advanced Cardiovascular Systems, Inc. | Multilayered biodegradable stent and method for its manufacture |
| DE69430699D1 (en) * | 1993-01-08 | 2002-07-04 | Miravant Syst Inc | DRUG DELIVERING STENTS |
-
1995
- 1995-10-17 EP EP95934320A patent/EP0761251B1/en not_active Expired - Lifetime
- 1995-10-17 AU AU36742/95A patent/AU699821B2/en not_active Ceased
- 1995-10-17 EP EP01126794A patent/EP1181904B1/en not_active Expired - Lifetime
- 1995-10-17 WO PCT/JP1995/002129 patent/WO1996011720A1/en active IP Right Grant
- 1995-10-17 EP EP04011417A patent/EP1477132A3/en not_active Withdrawn
- 1995-10-17 DE DE69535973T patent/DE69535973D1/en not_active Expired - Lifetime
- 1995-10-17 DE DE69533892T patent/DE69533892T2/en not_active Expired - Lifetime
- 1995-10-17 CA CA002179304A patent/CA2179304C/en not_active Expired - Fee Related
- 1995-10-17 AT AT01126794T patent/ATE434423T1/en not_active IP Right Cessation
- 1995-10-17 ES ES95934320T patent/ES2235174T3/en not_active Expired - Lifetime
- 1995-10-17 US US08/663,173 patent/US5733327A/en not_active Expired - Lifetime
- 1995-10-17 AT AT95934320T patent/ATE285813T1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE69533892D1 (en) | 2005-02-03 |
| EP0761251A1 (en) | 1997-03-12 |
| DE69533892T2 (en) | 2005-12-08 |
| US5733327A (en) | 1998-03-31 |
| AU3674295A (en) | 1996-05-06 |
| EP0761251A4 (en) | 1999-03-31 |
| EP1477132A2 (en) | 2004-11-17 |
| WO1996011720A1 (en) | 1996-04-25 |
| EP1181904B1 (en) | 2009-06-24 |
| AU699821B2 (en) | 1998-12-17 |
| CA2179304A1 (en) | 1996-04-25 |
| EP0761251B1 (en) | 2004-12-29 |
| ES2235174T3 (en) | 2005-07-01 |
| ATE285813T1 (en) | 2005-01-15 |
| EP1477132A3 (en) | 2009-09-09 |
| ATE434423T1 (en) | 2009-07-15 |
| EP1181904A3 (en) | 2003-07-16 |
| DE69535973D1 (en) | 2009-08-06 |
| EP1181904A2 (en) | 2002-02-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20151019 |