JP2005168646A - Stent and production method therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a stent which stresses a viable tissue little, has mechanical strength required for keeping a lumen in a living body patent until a probability of the occurrence of restinosis is nearly eliminated, and which never remains permanently as a foreign matter in the living body. <P>SOLUTION: The stent is formed of fibers having a composition containing biodegradable polymer and carbon fibers of 0.1 μm to 1.0 mm length. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a stent that is placed in a stenosis portion or an obstruction portion formed in a lumen in a living body such as a blood vessel, a bile duct, a trachea, an esophagus, or a urethra and maintained in an open state.

In recent years, a medical device called a stent has been used in order to improve a narrowed portion generated in a lumen in a living body such as a blood vessel, a bile duct, a trachea, an esophagus, and a urethra. In order to treat various diseases caused by stenosis or occlusion of blood vessels or other lumens, stents are used to expand lesions that are stenosis or occlusions and keep their lumens open. It is a hollow tubular medical device that can be placed there.
For example, the coronary artery of the heart is used for the purpose of preventing restenosis after percutaneous coronary angioplasty (PTCA).

  As this type of stent, a metal stent such as stainless steel has been conventionally used. Since a metal stent is hard, it gives stress to living tissue, causes inflammation and excessive thickening in the lumen of the living body, and causes restenosis. In addition, the metal stent has a problem that it remains permanently as a foreign substance in the living body.

As a means for solving these problems, a stent made of a biodegradable polymer has been proposed (for example, see Patent Document 1). A stent made of a biodegradable polymer is flexible compared to a metal stent, and therefore has less stress on living tissue, and is less likely to cause inflammation and excessive thickening that cause restenosis. In addition, when a stent made of a biodegradable polymer is placed in the living body, the polymer constituting the stent is decomposed over time and absorbed by the living body, so that it does not eventually remain in the body. However, a stent made of a biodegradable polymer has a reduced mechanical strength as the biodegradable polymer progresses, so that the probability of restenosis almost disappears (eg, the stent is placed in a blood vessel). In this case, until the site where the stent is placed is covered with vascular endothelial cells), the mechanical strength necessary for maintaining the lumen in the living body cannot be obtained, and as a result, restenosis is prevented. There was a problem that could happen.
Japanese Patent No. 2842943

  The present invention has the mechanical strength necessary to maintain the lumen in the living body in an open state until the stress applied to the living tissue is small and the probability of restenosis is almost eliminated. An object is to provide a stent that does not remain permanently.

As a result of intensive studies by the present inventors, as a material constituting the stent, a composition composed of a biodegradable polymer and fine carbon fibers is used in a fiber shape, and compared with a metal stent. Since the biodegradable polymer and the carbon fiber are present in the fibrous composition, the mechanical properties of the stent due to the degradation of the biodegradable polymer are small. It was found that the biodegradable polymer was decomposed and absorbed with time, and the fine carbon fibers were present in the living body in an inactive state for living organisms, and the present invention was completed.
Such an object is achieved by the present inventions (1) to (12) shown below.

  (1) A stent formed of fibers of a composition containing a biodegradable polymer and carbon fibers having a length of 0.1 μm to 1.0 mm.

  (2) The stent according to (1), wherein the carbon fiber has a length of 0.1 μm to 100 μm.

  (3) The stent according to (1) or (2), wherein the carbon fiber has a graphite layer having a carbon 6-membered ring structure as a main structure.

  (4) The stent according to (1) or (2), wherein the carbon fiber has a helical cylindrical structure made of a graphite sheet having a carbon 6-membered ring structure as a main structure.

  (5) The stent according to any one of (1) to (4), wherein an outer diameter of the carbon fiber is 0.4 nm to 300 nm.

  (6) The biodegradable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, poly (ε-caprolactone), polyhydroxybutyric acid, polydioxanone, copolymers thereof, and blends of these polymers. The stent according to any one of (1) to (5), wherein the stent is at least one.

  (7) The stent according to any one of (1) to (6), wherein the composition contains a biologically physiologically active substance.

  (8) The content rate of the said carbon fiber with respect to the total mass of the said biodegradable polymer and the said carbon fiber in the said composition is any one of said (1)-(7) which is 0.1-50 mass%. Stent.

(9) A method for producing a stent having the following steps.
1. A first step of preparing a composition by mixing biodegradable polymer powder and carbon fiber having a length of 0.1 μm to 1.0 mm.
2. A second step of converting the composition obtained in the first step into fibers.
3. A third step of forming the fiber obtained in the second step into a stent shape.

  (10) The method for producing a stent according to (9), wherein the biodegradable polymer powder used in the first step has an average particle diameter of 1 to 150 μm.

  (11) The method for producing a stent according to (10), wherein the biodegradable polymer powder used in the first step is prepared by a chemical pulverization method.

  (12) The method for manufacturing a stent according to any one of (9) to (11), wherein the fibers are stretched and oriented during the second step or after the second step.

  The stent of the present invention has a mechanical strength necessary for maintaining the lumen in the living body in an open state until the stress applied to the living tissue is small and the probability of restenosis is almost eliminated. It does not remain permanently as a foreign object.

Below, the stent of this invention and its manufacturing method are demonstrated in detail.
The stent of the present invention is a stent formed of fibers of a composition containing a biodegradable polymer and carbon fibers having a length of 0.1 μm to 1.0 mm.

  The fibers forming the stent of the present invention are composed of a composition that is a homogeneous mixture of a biodegradable polymer and carbon fibers having a length of 0.1 μm to 1.0 mm. Hereinafter, the carbon fiber and the biodegradable polymer constituting the composition of the present invention will be described in detail.

<Carbon fiber>
As the carbon fiber of the present invention, one having a graphite layer having a carbon 6-membered ring structure as a main structure can be used. The carbon fiber having such a structure is generally called a carbon fiber, a carbon nanotube, or the like, and can take any shape such as a needle shape, a spiral shape, and a cylindrical shape. In addition, the carbon fibers are not limited to those dispersed alone, but may be ones that form aggregates.

  Specifically, the carbon fiber having a graphite layer having a carbon 6-membered ring as a main structure, specifically, a carbon fiber having a helical cylindrical structure made of a graphite sheet having a carbon 6-membered ring structure as a main structure (generally “carbon” Nanotubes "), and a graphite fiber having a multiple structure formed of a helical structure composed of a graphite layer having a carbon 6-membered ring structure as a main structure, and the end of the fiber ends in a conical shape. A graphite fiber having a cylindrical structure (generally also referred to as “carbon nanohorn”) is exemplified. The carbon nanotube may have a single-layer cylindrical structure (for example, a carbon fiber described in Japanese Patent No. 2526778), or a multi-layer structure in which cylindrical shapes formed in a spiral structure are arranged concentrically. (For example, carbon fiber described in Nature, 354, 56 (1991), Japanese Patent No. 2687794, etc.) may be used. When a carbon nanotube is used as the carbon fiber, a preferable outer diameter range of the carbon fiber described later can be satisfied, and the carbon fiber has high flexibility and excellent biocompatibility. When indwelling, the possibility of inducing inflammation and intimal thickening at the indwelling location is reduced, which is preferable.

  The carbon nanohorn may have a multi-layer structure in which one layer or two or more layers are stacked (for example, carbon fiber described in Japanese Patent No. 2705447). Moreover, the thing of the aggregate | assembly (for example, Unexamined-Japanese-Patent No. 2002-159851 etc.) with the square cylindrical structure turned toward the outer side may be sufficient. These carbon nanohorns are also preferable as the carbon fiber of the present invention for the same reason as the carbon nanotube.

  The carbon fiber may have a length of 0.1 μm to 1.0 mm, preferably 0.1 to 100 μm. Within such a length range, it is easy to produce as a fiber, there is no secondary aggregation due to entanglement between carbon fibers, and it can be uniformly dispersed with the biodegradable polymer in the composition. . In particular, when the carbon fiber has a length of 1.0 to 50 μm, the carbon fiber and the biodegradable polymer powder are appropriately entangled with each other, so that the mechanical strength of the stent due to the decomposition of the biodegradable polymer is reduced. Since a fall can be suppressed, it is more preferable.

  The outer diameter of the carbon fiber is preferably 0.4 nm to 300 nm. Carbon fibers having an outer diameter in this range are relatively readily available and have adequate flexibility, so that the stress applied to living tissue is small, which induces inflammation and excessive thickening that cause restenosis It is unlikely, and even after the biodegradable polymer has been degraded, it can exist in an inactive state for the organism in the body. The outer diameter of the carbon fiber is more preferably 0.8 to 200 nm because it can be obtained with a high yield in a known production method and is easily commercially available, and the carbon fiber has moderate flexibility.

  The above-described carbon fiber can be produced by a known carbon fiber production method (for example, Takashi Yoshida, “Basics of Carbon Nanotubes and Forefront of Industrialization”, first edition, NTS Corporation, 2002 1). 11th, p. 6-18, JP 2003-238130 A). In general, an arc discharge method, a laser evaporation method, a catalytic vapor phase growth method, or the like is often used.

  As an example of the arc discharge method, carbon electrodes are placed in a vacuum chamber facing each other with an interval of 1 to 2 mm, and after the inside of the chamber is evacuated, a helium gas or the like is flowed to adjust the pressure to about 50 to 1500 Torr. And a current is passed with a direct current of 60 to 100A. Then, carbon evaporates from the anode, a part of it is deposited on the cathode surface, and many of them form soot outside the discharge space. The carbon fibers contained in these cathode deposits or soot formed outside the discharge space are purified by ultrasonic irradiation, centrifugal sedimentation, oxidation, etc. to obtain carbon fibers.

  As an example of the laser evaporation method, a graphite rod is installed in a quartz tube, a metal is coated in the graphite rod, argon gas or the like is flown into the quartz tube, the pressure is increased to about 500 Torr, When laser light is irradiated while heating to 1400 ° C., soot adheres to the quartz tube wall. The carbon fiber in the soot is purified in the same manner as described above to obtain the carbon fiber.

  As an example of the catalytic vapor phase growth method, an apparatus including an electric furnace, a carrier gas supply unit, a hydrocarbon supply unit, and the like is used. Hydrocarbon vapor is put on a carrier gas such as argon gas and sent into an electric furnace. An appropriate substrate is placed here, and metal-based fine particles, ferrocene, or the like is applied thereon, or is sprayed between the cores like a spray, and heated to a high temperature (about 1000 ° C.). The soot formed on the substrate is purified in the same manner as described above to obtain carbon fibers.

  In the course of performing these production methods, carbon fibers having different structures can be produced depending on production conditions such as temperature and atmospheric gas, the type of catalyst, and the like. Moreover, you may manufacture using methods other than these manufacturing methods.

  The carbon fiber does not necessarily have to be as manufactured, and may be subjected to treatment such as heat treatment, fragmentation treatment, and chemical modification treatment. By performing these treatments, the adhesion between the carbon fiber and the biodegradable polymer is strengthened, and the mechanical strength in the biodegradation and absorption process of the stent is further increased, which is preferable.

<Biodegradable polymer>
The biodegradable polymer of the present invention is not particularly limited as long as it is a material that can be safely decomposed and absorbed in vivo. By using such a polymer, the stent does not remain permanently as a foreign substance in the body like a metal stent.
Examples of the biodegradable polymer include polylactic acid, polyglycolic acid, poly (ε-caprolactone), polyhydroxybutyric acid, polydioxanone, a copolymer of two or more of these, and a blend of two or more of these polymers. Is mentioned. Among these, polylactic acid has been used in the medical field as an implant material for bone screws and the like, and has high biocompatibility. preferable.

  The biodegradable polymer preferably has a weight average molecular weight of 10,000 to 1,000,000 so as to have appropriate moldability when mixed with carbon fiber or the like to form a fiber. More preferably, the weight average molecular weight is 100,000 to 500,000.

The fiber of this invention is comprised from the composition containing the said biodegradable polymer and the said carbon fiber. In addition to these, the composition may contain, for example, an X-ray contrast agent or a biological physiologically active substance.
The X-ray contrast agent, biological physiologically active substance, and the like may be mixed with the biodegradable polymer and the carbon fiber to form a fiber, or may be contained in the biodegradable polymer in advance. For example, when a stent composed of fibers containing a biologically bioactive substance contained in a biodegradable polymer is placed in a living body, the biodegradable polymer is degraded in vivo. The physiologically active substance is preferable because it can be gradually released and the lesion can be effectively treated.

  The biologically active substance is not particularly limited, but preferably has an effect of suppressing restenosis when the stent of the present invention is placed in a lesioned part of a living body lumen. Specifically, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, antihyperlipidemic agents, ACE inhibitors, calcium antagonists, integrin inhibitors, antiallergic agents, antioxidants Agents, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, anti-inflammatory agents, biomaterials, interferons, etc., but in terms of dosage and medicinal properties, paclitaxel Anticancer agents such as are most preferably used.

  More specifically, as the anticancer agent, for example, vincristine sulfate, vinblastine sulfate, vindesine sulfate, irinotecan hydrochloride, paclitaxel, docetaxel hydrate, methotrexate, cyclophosphamide and the like are preferable.

  More specifically, as an immunosuppressant, for example, sirolimus, tacrolimus hydrate, azathioprine, cyclosporine, mycophenolate mofetil, gusperimus hydrochloride, mizoribine and the like are preferable.

  More specifically, as the antibiotic, for example, mitomycin C, doxorubicin hydrochloride, actinomycin D, daunorubicin hydrochloride, idarubicin hydrochloride, pirarubicin hydrochloride, aclarubicin hydrochloride, epirubicin hydrochloride, pepromycin sulfate, dinostatin stimaramer and the like are preferable.

  More specifically, the antirheumatic agent is preferably, for example, sodium gold thiomalate, penicillamine, lobenzalit disodium or the like.

  More specifically, as an antithrombotic agent, for example, heparin, ticlopidine hydrochloride, hirudin and the like are preferable.

  More specifically, the antihyperlipidemic agent is preferably an HMG-CoA reductase inhibitor or probucol. As the HMG-CoA reductase inhibitor, more specifically, for example, cerivastatin sodium, atorvastatin, nisvastatin, pitavastatin, fluvastatin sodium, simvastatin, lovastatin, pravastatin sodium and the like are preferable.

  More specific examples of the ACE inhibitor include quinapril hydrochloride, perindopril erbumine, trandolapril, cilazapril, temocapril hydrochloride, delapril hydrochloride, enalapril maleate, lisinopril, captopril and the like.

  More specifically, as the calcium antagonist, for example, nifedipine, nilvadipine, diltiazem hydrochloride, benidipine hydrochloride, nisoldipine and the like are preferable.

  More specifically, for example, tranilast is preferable as the antiallergic agent.

  More specifically, for example, all-trans retinoic acid is preferable as the retinoid.

  More specifically, as an antioxidant, for example, catechins, anthocyanins, proanthocyanidins, lycopene, β-carotene and the like are preferable. Among catechins, epigallocatechin gallate is particularly preferable.

  More specifically, as a tyrosine kinase inhibitor, for example, genistein, tyrphostin, arbustatin and the like are preferable.

  More specifically, as an anti-inflammatory agent, for example, steroids such as dexamethasone and prednisolone and aspirin are preferable.

  More specifically, examples of the bio-derived material include EGF (epidemal growth factor), VEGF (basic endorthous growth factor), HGF (hepatocyte growth factor), PDGF (platelet growth factor), PDGF (platelet growth factor), and PDGF (platelet growth factor). Etc.) are preferred.

<Manufacturing method>
The stent of the present invention is manufactured by the following steps.
(1) A first step of preparing a composition by mixing biodegradable polymer powder and carbon fiber having a length of 0.1 μm to 1.0 mm.
(2) A second step in which the composition containing the biodegradable polymer and carbon fiber obtained in the first step is made into a fiber.
(3) A third step of forming the fiber obtained in the second step into a stent shape.

  The first step includes a step (mixing step) of mixing the biodegradable polymer and the carbon fiber, if necessary, an X-ray contrast agent, a biological physiologically active substance, etc. under dry or wet conditions, and if necessary. And a step (preparation step) of forming the mixture by melt-kneading extrusion or the like.

In the mixing step, a known method can be used as the mixing method, and it is desirable that the mixing is performed uniformly in a dry or wet manner. For example, the method etc. which mix using mixing apparatuses, such as a dispersion | distribution mixing stirrer, are mentioned.
In the mixing step, the biodegradable polymer used is preferably a powder prepared by a chemical pulverization method described later. In the above fiber, if the biodegradable polymer is powdery prepared by a chemical pulverization method, the surface of the biodegradable polymer is smooth, so that the carbon fibers can be uniformly dispersed and the mechanical strength is improved. Since the carbon fibers do not aggregate in part, biocompatibility is enhanced.
It is more preferable to use a powdery biodegradable polymer having an average particle diameter of 1 μm to 150 μm. A biodegradable polymer powder in this range is relatively easy to produce, and the carbon fibers can be uniformly dispersed when mixed with the carbon fibers.

  A method for adjusting the biodegradable polymer to a powdery biodegradable polymer having an average particle diameter of 1 μm to 150 μm is not particularly limited, but it is preferably prepared by a chemical pulverization method. In this specification, the chemical pulverization method is a method using a principle generally called spinodal decomposition (for example, see JP-A-4-339828). For example, after a biodegradable polymer is heated and dissolved and mixed in a solvent. Examples of the method include obtaining a powder having a predetermined particle size range by washing, drying, crushing, and classifying the powder deposited by cooling. By using this method, a powdery biodegradable polymer having an average particle diameter of 1 μm to 150 μm can be prepared for many biodegradable polymers including polylactic acid. Furthermore, since the powdery biodegradable polymer obtained by this method has a smooth surface and a spherical shape, it is easily entangled with the carbon fiber, which is convenient for the resulting composition to achieve an appropriate mechanical strength.

  The content of carbon fiber relative to the total mass of the biodegradable polymer and the carbon fiber in the composition of the present invention (hereinafter also simply referred to as “carbon fiber content”) is 0.1 to 50% by mass. Is desirable. If the carbon fiber content is less than 0.1% by mass, the degradation of the mechanical strength of the stent due to the degradation of the biodegradable polymer cannot be suppressed. May be difficult to do. A more preferable carbon fiber content is 10 to 30% by mass. Within this range, even in the process in which the biodegradable polymer is decomposed and absorbed in the living body, sufficient mechanical strength to support the lumen in the living body such as a blood vessel is realized, and the stent is formed from the fiber. Good shape-giving ability when molding.

  The preparation step is not particularly limited. For example, the mixture mixed in the mixing step is melt-kneaded using a biaxial kneader, and biodegradable polymer, carbon fiber, X-ray contrast agent, biological physiological It is a step of adjusting a composition containing an active substance or the like into a pellet shape. The shape of the composition is not limited to pellets, and those obtained in the mixing step may be used directly as they are, or may be used as powders.

  The second step is a step of converting the composition containing the biodegradable polymer and carbon fiber obtained in the first step into fibers. The method for forming the fiber is not particularly limited, and examples thereof include a melt spinning method, a dry spinning method, and a wet spinning method.

  In order to give the fiber sufficient mechanical strength to support the lumen in the living body, the fiber may be stretched and oriented at an appropriate draw ratio during the second step or after the second step. Good. When the fiber is stretched and oriented after the second step, the fiber is preferably heated to an appropriate temperature. This stretching orientation is preferable because the biodegradable polymer and carbon fibers contained in the fiber are oriented and crystallized, and the mechanical strength of the stent can be improved.

  The outer diameter of the fiber is preferably 80 μm to 150 μm from the viewpoint of mechanical strength of a stent made of the fiber and ease of forming into a stent shape described later.

  The third step is a step of forming the fiber obtained in the second step into a stent shape. The shape of the stent and the molding method are not particularly limited. For example, a stent formed into a tubular body by knitting one or two fibers obtained in the second step (for example, in the specification of Japanese Patent No. 2961287) A mesh-shaped stent according to the flat knitting) described above; a stent in which a fiber is wound into a tubular shape to form a coiled tubular body (see, for example, Japanese Patent Laid-Open No. 11-137694); Preferred examples include the shape of a stent wound in a shape (for example, a stent described in JP-A-2002-239013) and a molding method. These may be heat-treated one or more times in order to achieve good shaping.

  FIG. 1 is an example of a projected view of a stent described in JP-A-2002-239013 from the lateral direction. The stent 1 is a stent in which a wavy or zigzag-shaped fiber is wound into a cylindrical shape, sandwiched between plate-like jigs, and compressed to form a wavy or zigzag molded product. In the stent formation step, heat treatment is performed at least twice, the heat treatment condition is not less than the glass transition of the fiber and not more than the melting point, and further the heat treatment temperature after that is set to be higher than the first heat treatment. And

  The stent of the present invention is not limited to the above-described embodiment, and is a cylindrical body that is open at both end portions and extends in the longitudinal direction between the both end portions. The structure includes a large number of notches that communicate with each other, and by deforming the notches, a structure that can be expanded and contracted in the radial direction of the cylindrical body is widely included.

  As specific examples of the stent shape having such a structure that can be expanded and contracted in the radial direction, for example, an elastic wire as disclosed in Japanese Patent Laid-Open Nos. 9-215753 and 7-529 is bent into a coil shape. A plurality of stents connected to each other to form a cylindrical shape; as disclosed in JP-A-8-502428 and JP-A-7-5000027, an elastic wire is bent in a zigzag shape to A plurality of stents connected to each other to form a cylindrical shape; as disclosed in JP-T-2000-501328 and JP-A-11-212288, an elastic wire is bent into the shape of a snake-like flat ribbon. A stent which is wound around a mandrel in a helix shape and formed into a cylindrical shape; a stent having a mesh-like structure as disclosed in JP-T-10-503676 As disclosed in KOKOKU 4-68939 discloses, braided stents or the like which is in a cylindrical shape and the like of the elastic wire. In addition, the stent may have a multiple spiral shape, a modified tubular shape, or the like. All of these above references and patent applications are hereby incorporated by reference.

  The size of the stent may be appropriately selected according to the application site. For example, when used for the coronary artery of the heart, the outer diameter before expansion is usually 1.0 to 3.0 mm, and the length is preferably 5 to 50 mm.

  The expansion means of the stent body is not particularly limited, and may be of a self-expanding type, that is, a type that expands in the radial direction by its own restoring force by removing the force holding the stent body that is finely and smallly folded. Well, it may be of the balloon expandable type, that is, a type in which the balloon is expanded from the inside of the stent body and expanded radially by an external force.

  To place a balloon-expandable stent at a target site, the catheter is inserted into the target site, then the balloon is positioned in the stent, the balloon is expanded, and the stent is expanded (plastic deformation) by the expansion force of the balloon. ) And fix it in close contact with the inner surface of the target site.

  When the stent itself has contraction and expansion functions, the stent is contracted and inserted into the target site, and then the stress applied to maintain the contracted state is removed. For example, the stent is contracted and accommodated in a tube having an outer diameter smaller than the inner diameter of the target site, and after the distal end of the tube reaches the target site, the stent is pushed out from the tube. The extruded stent is released from the tube to release the stress load, and restores and expands to the shape before contraction. Thereby, it adheres and fixes to the inner surface of the biological organ (for example, blood vessel) of the target part.

  The stent of the present invention is flexible compared to a metal stent by using a composition comprising a biodegradable polymer and fine carbon fibers in the form of a fiber as a material constituting the stent. Therefore, the stress applied to the living tissue is small, and the possibility of causing inflammation and excessive thickening that cause restenosis is small. Further, the presence of the biodegradable polymer and the carbon fiber in the fibrous composition suppresses a decrease in the mechanical strength of the stent due to the degradation of the biodegradable polymer, and there is almost no probability of restenosis. It has the mechanical strength necessary to keep the lumen in the living body open until it disappears. Furthermore, when the stent is placed in the living body, the biodegradable polymer is decomposed and absorbed over time, and the fine carbon fibers are taken into the living body and exist in an inactive state in the living body. As a result, it will not remain in the body as a foreign body.

Hereinafter, the stent of the present invention will be described in detail according to examples. However, the present invention is not limited to this.
(Example 1)
(1) Grinding of biodegradable polymer (chemical grinding method)
Polylactic acid pellets (LACTY # 9010, weight average molecular weight 170,000, manufactured by Shimadzu Corporation) and xylene (domestic chemical special grade I158791) are placed in a dissolution tank so that polylactic acid is 5% by mass and stirred at a slow speed. The solution was heated and dissolved at 80 to 120 ° C. When the solution became transparent, heating was stopped, and the solution was gradually cooled to room temperature to precipitate polylactic acid fine particles. The solution was filtered to collect the polylactic acid fine particles and washed with water, and then the solvent was completely evaporated at 65 ° C. or lower in a stirring vacuum dryer. The obtained powdery polylactic acid was classified with an appropriate sieve, and a desired powdery polylactic acid powder having an average particle size of 100 μm was obtained.

(2) Preparation of composition 4.5 kg of polylactic acid powder produced in (1), 0.5 kg of multi-walled carbon nanotubes (Multi-walled carbon nanotubes, manufactured by Wako Chemical Co., Ltd.), and X-ray 1.5 kg of barium sulfate for imparting contrast was mixed using a dispersion mixing stirrer to obtain a composition powder (carbon fiber content 10 mass%) in which these were uniformly mixed. This was melt kneaded at a temperature of 180 ° C. and a rotation speed of 80 rpm using a biaxial kneader (S1KRC kneader, manufactured by Kurimoto Steel Co., Ltd.) to obtain composition pellets.

(3) Fiberizing step Using the high-temperature melt spinning apparatus (CM / TM-35 mm, manufactured by Chubu Chemical Machinery Co., Ltd.), the composition pellets obtained in (2) are subjected to a cylinder temperature of 200 ° C. and a gear pump rotational speed. Melt spinning was performed at 4 rpm and a take-up speed of 37 m / min, and the obtained fiber was stretched 5 times at 80 ° C. to obtain a fiber having a diameter of 150 μm.

(4) Shape imparting step Shaped by the method described in Japanese Patent Application Laid-Open No. 2002-239013 described above, a stent formed by winding a fiber bent in a wave shape into a tubular shape was manufactured.

(Example 2)
A stent was produced in the same manner as in Example 1 except that the outer diameter of the carbon fiber was 100 nm.

(Example 3)
A stent was produced in the same manner as in Example 1 except that the length of the carbon fiber was 60 to 80 μm.

Example 4
A stent was produced in the same manner as in Example 1 except that the average particle size of the biodegradable polymer was 45 μm.

(Example 5)
A stent is produced in the same manner as in Example 1 except that a poly (lactic acid-glycolic acid) copolymer (RESOMER RG505, weight average molecular weight 350,000, manufactured by Boehringer Ingelheim) is used as the biodegradable polymer. did.

Example 6
A stent was produced in the same manner as in Example 1 using single-walled cylindrical carbon nanotubes (Single Walled carbon nanotubes, manufactured by Strem Chemical Co., Ltd.).

(Example 7)
A stent was produced in the same manner as in Example 1 except that the carbon fiber content was 30% by mass.

(Comparative Example 1)
A stent was manufactured in the same manner as in Example 1 without using carbon fiber.

(Comparative Example 2)
Except that the average particle size of the biodegradable polymer was changed to 504 μm, an attempt was made to produce a stent in the same manner as in Example 1, but the fibers could not be formed into a stent shape.

(Comparative Example 3)
A mechanical pulverization method was used as a pulverization method for the biodegradable polymer. Specifically, polylactic acid pellets (LACTY # 9010, weight average molecular weight 170,000, manufactured by Shimadzu Corporation) were cooled with liquefied nitrogen and pulverized with an impact-type freeze pulverizer (manufactured by Nippon Oxygen Co., Ltd.). The powdered polylactic acid was classified with a sieve having an appropriate opening to obtain powdered polylactic acid having an average particle size of 100 μm. Using this polylactic acid, a stent was produced in the same manner as in the method of Example 1.

(Comparative Example 4)
A stent was produced in the same manner as in Example 1 except that the carbon fiber content was set to 70% by mass. However, the stent could not be produced because it could not be made into a fiber.

(Comparative Example 5)
Using polyacrylonitrile fiber as a raw material, flameproofed in an air atmosphere at 200 to 300 ° C. in a high temperature furnace, then carbonized in argon gas at 1000 to 1500 ° C. to form a poly having an outer diameter of 5 to 6 μm and a length of 5 to 20 mm Acrylonitrile-based carbon fibers were produced. Except for using this carbon fiber, an attempt was made to produce a stent in the same manner as in Example 1, but the fiber could not be made into a stent shape.

<Evaluation>
In order to confirm the presence or absence of restenosis after indwelling the stents of Examples 1 to 7 and Comparative Examples 1 and 3 in the stenosis part of the coronary artery blood vessel of the pig using a balloon catheter, and leaving for 3 months, X-ray imaging The presence or absence of blood flow at the stent placement site was confirmed.
The case where blood flow could be confirmed is set as “◯”, and the case where blood flow was not confirmed is set as “X”. In addition, Comparative Examples 2, 4, and 5 in which the stent could not be manufactured are not evaluated. The results are shown in Table 1.

From the results shown in Table 1, the stents of Examples 1 to 7 did not cause restenosis since the mechanical strength of the stent could be maintained even after being placed in the stenosis portion in the blood vessel. On the other hand, in the stents of Comparative Examples 1 and 3, after being placed in the stenosis portion in the blood vessel, the mechanical strength of the stent is remarkably lowered, and sufficient mechanical strength to support the blood vessel cannot be obtained. occured. In both Comparative Examples 2 and 5, the polylactic acid and the carbon fiber were not uniformly dispersed, so that the fiber could not be formed into a stent shape. Further, Comparative Example 4 could not be made into fibers.

Claims (12)

  A stent formed of fibers of a composition containing a biodegradable polymer and carbon fibers having a length of 0.1 μm to 1.0 mm.   The stent according to claim 1, wherein the carbon fiber has a length of 0.1 μm to 100 μm.   The stent according to claim 1 or 2, wherein the carbon fiber has a graphite layer having a carbon 6-membered ring structure as a main structure.   The stent according to claim 1 or 2, wherein the carbon fiber has a helical cylindrical structure made of a graphite sheet having a carbon 6-membered ring structure as a main structure.   The stent according to any one of claims 1 to 4, wherein an outer diameter of the carbon fiber is 0.4 nm to 300 nm.   The biodegradable polymer is at least one selected from the group consisting of polylactic acid, polyglycolic acid, poly (ε-caprolactone), polyhydroxybutyric acid, polydioxanone, copolymers thereof, and blends of these polymers. The stent according to any one of claims 1 to 5.   The stent according to any one of claims 1 to 6, wherein the composition contains a biological physiologically active substance.   The stent according to any one of claims 1 to 7, wherein a content rate of the carbon fiber with respect to a total mass of the biodegradable polymer and the carbon fiber in the composition is 0.1 to 50% by mass. The manufacturing method of the stent which has each following process.
(1) A first step of preparing a composition by mixing biodegradable polymer powder and carbon fiber having a length of 0.1 μm to 1.0 mm.
(2) A second step in which the composition obtained in the first step is made into a fiber.
(3) A third step of forming the fiber obtained in the second step into a stent shape.   The method for producing a stent according to claim 9, wherein the biodegradable polymer powder used in the first step has an average particle diameter of 1 to 150 μm.   The stent manufacturing method according to claim 10, wherein the biodegradable polymer powder used in the first step is prepared by a chemical pulverization method. The method for manufacturing a stent according to any one of claims 9 to 11, wherein the fibers are stretched and oriented during the second step or after the second step.