JP2006198078A - Stent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a stent eliminating any possibility of breaking a biodegradable composition on the surface of the stent by inflation when being used in the body, releasing medical agent at an intended speed from the surface of a stent body, sufficiently internally fixing the stent to a balloon when installing the stent to the balloon and eliminating any possibility of lowering the gripping force of the stent on the balloon and the falling of the stent. <P>SOLUTION: In the stent, the surface of the stent body is provided with a biologically and physiologically active substance and the biodegradable composition formed of polymer being solid under a room temperature and degraded in the body, an additive, and has a Young's modulus by a tensile test of 100 MPa or more, elongation at a yield point of 20% or less, and elongation at a fracture point of 40% or more. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a stent that expands a stenosis part, an obstruction part, etc. generated in a living body such as a blood vessel, a bile duct, a trachea, an esophagus, a urethra, and other organs.

  In recent years, a medical device called a stent has been used in order to improve a stenosis part, an obstruction part, and the like generated in a lumen in a living body such as a blood vessel, a bile duct, a trachea, a canteen, and a urethra. In order to treat various diseases caused by stenosis or occlusion of a lumen of a blood vessel or the like, a stent is used to expand a lesion part such as a stenosis part or an obstruction part and make the lumen open. In order to maintain, it is a hollow tubular medical device which can be detained in the said site | part. For example, in the coronary artery of the heart, it is used for the purpose of preventing restenosis after percutaneous coronary angioplasty (PTCA). By placing a hollow tubular medical device called a stent in a lumen such as a blood vessel after surgery or the like, the incidence of acute vascular occlusion and restenosis can be reduced.

  However, it has been confirmed by follow-up after half a year that restenosis occurs at an average rate of about 30% at the stent placement site, and the problem of restenosis remains a major issue.

  Therefore, a stent that suppresses restenosis has been proposed in which a biological physiologically active substance such as an anticancer agent or an immunosuppressive agent is supported on the surface of the stent body. For example, Patent Document 1 is manufactured by applying a solution containing a solvent, a polymer dissolved in the solvent, and a therapeutic substance dispersed in the solvent to the main body of the stent, and evaporating the solvent. Stents are described. According to this document, the stent manufactured in this manner is selected without losing a therapeutically important amount of the drug because the surface of the stent body is coated with a polymer and a therapeutic substance. It is described that the drug can be continuously released and delivered.

In this way, the surface of the stent body is provided with a drug (biological and physiologically active substance) and a polymer, and the drug is supported by the polymer, so that the drug can be reliably delivered to the target site, Stents that can release drug continuously are known in the art.
However, when such a stent is used in an environment of about room temperature, the polymer on the surface of the stent body does not stretch easily, and there is a risk that it will break due to a crack or the like. In this case, the release rate of the drug from the surface of the stent body in the living body may change from a desired one. This can occur whether the stent is self-expanding or balloon-expanding.

In addition, for example, in the case of a balloon expandable stent, if priority is given to preventing the polymer layer from being destroyed when the stent is attached to the balloon, the stent may not be sufficiently caulked to the balloon. There is a concern about a decrease in gripping force on the balloon and even a drop of the stent.
JP-A-8-33718

  The problems to be solved by the present invention include a biodegradable composition comprising a biological physiologically active substance, a polymer that is solid at room temperature and decomposes in vivo, and an additive on the surface of the stent body. The biodegradable composition on the stent surface is not destroyed by expansion when used in vivo, and the drug is released from the surface of the stent body at a desired rate. It is an object of the present invention to provide a stent in which a sufficient caulking operation of the stent to the balloon can be performed when the stent is attached to the balloon, and there is no fear of a decrease in the gripping force of the stent on the balloon and, further, a dropout of the stent.

  The present invention provides the following stents in order to solve the above problems.

  The present invention comprises a biological and physiologically active substance on a surface of a stent body, a polymer which is solid at room temperature and decomposes in vivo, and an additive having a Young's modulus of 100 MPa or more by a tensile test, and yielding. And a biodegradable composition having an elongation (strain) at a point of 20% or less and an elongation (strain) at a break point of 40% or more.

  In such a stent, the biodegradable composition preferably has an absolute value of a difference between a yield point stress and a breakpoint stress by a tensile test of 30% or less of the yield point stress.

  The biodegradable composition is preferably produced by kneading the polymer and the additive at a temperature of 0 ° C. or higher and lower than the melting temperature of the polymer.

  Moreover, it is preferable that the said stent main body is a metal material.

  Moreover, it is preferable that the said stent main body consists of the said biodegradable composition.

  The polymer is preferably polyester.

  Moreover, it is preferable that the said additive is a biocompatible compound.

  Moreover, it is preferable to have the layer which consists of the said biological bioactive substance on the surface of the said stent main body, and also to have the layer which consists of the said biodegradable composition on the upper surface.

  Moreover, it is preferable to have the layer which consists of the said biological physiologically active substance and the said biodegradable composition on the surface of the said stent main body.

  Further, the biological physiologically active substance is an anticancer agent, immunosuppressant, antibiotic, antirheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemic agent , Integrin inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet agents, anti-inflammatory agents, biological materials, interferon And at least one selected from the group consisting of NO production promoting substances.

  The stent of the present invention has a biodegradable composition comprising a biological physiologically active substance, a polymer that is solid at room temperature and decomposes in vivo, and an additive on the surface of the stent body, Expansion in use allows the drug to be released from the surface of the stent body at the desired rate without the risk of breaking because the biodegradable composition on the stent surface will stretch easily. Further, when the stent is attached to the balloon, a sufficient caulking operation to the balloon of the stent can be performed, and there is no concern about a decrease in the gripping force of the stent on the balloon or even a drop of the stent.

  In the stent of the present invention, it is preferable that the stent main body is made of a metal material, and thus the metal material is excellent in strength, so that the stent can be surely placed in the lesion. .

  In the stent of the present invention, it is preferable that the stent body is made of the biodegradable composition, and as a result, the entire stent is degraded in vivo after a certain period of time. There is an effect that it is possible to prevent an adverse effect on the living body due to the presence of the stent in the living body without performing reoperation.

  In the stent of the present invention, it is preferable that the polymer is a polyester, thereby exhibiting an effect of high biocompatibility.

  In the stent of the present invention, it is preferable that the additive is a biocompatible compound, which has the effect of further increasing biocompatibility.

  Further, in the stent of the present invention, it is preferable that the surface of the stent body has a layer made of the biological physiologically active substance, and further has a layer made of the biodegradable composition on the upper surface. As a result, the biological physiologically active substance can be stabilized and the biological physiologically active substance can be gradually released into the living body.

  In the stent of the present invention, it is preferable that the surface of the stent body has a layer composed of the biological physiologically active substance and the biodegradable composition, whereby the biodegradable composition is formed. As the substance is decomposed, the biological and physiologically active substance is gradually released into the living body, and an appropriate treatment can be performed.

  In the stent of the present invention, the biological physiologically active substance is an anticancer agent, immunosuppressive agent, antibiotic, antirheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist. Antihyperlipidemic agent, integrin inhibitor, antiallergic agent, antioxidant, GPIIbIIIa antagonist, retinoid, flavonoid, carotenoid, lipid improver, DNA synthesis inhibitor, tyrosine kinase inhibitor, antiplatelet agent, anti-inflammatory It is preferably at least one selected from the group consisting of a drug, a biological material, an interferon, and a NO production promoting substance, whereby the behavior of the lesion can be treated by controlling the behavior of cells in the lesion tissue. There is an effect that can be done.

The stent of the present invention has, on the surface of the stent body, a biophysiologically active substance, a biodegradable composition comprising a polymer that is solid at room temperature and decomposes in vivo and an additive.
Hereinafter, this stent body is also referred to as “the stent body of the present invention”.
Hereinafter, this biological physiologically active substance is also referred to as “the biological physiologically active substance of the present invention”.

Hereinafter, a polymer that is solid at room temperature and decomposes in vivo is also referred to as “degradable polymer of the present invention”.
Here, “solid at room temperature” means “solid at room temperature of temperature 23 ± 2 ° C. and relative humidity 50 ± 5 ° C.”.
Hereinafter, the biodegradable composition comprising the degradable polymer of the present invention and an additive is also referred to as “the biodegradable composition of the present invention”.

<Degradable polymer of the present invention>
The degradable polymer of the present invention is not particularly limited as long as it is a polymer that is solid at room temperature and decomposes in vivo. Among these, polyester that decomposes in vivo (hereinafter also referred to as “degradable polyester”) is preferable. The degradable polymer of the present invention preferably has biocompatibility.

  The degradable polyester is preferably obtained from at least one selected from the group consisting of lactic acid, glycolic acid (hydroxyacetic acid), caprolactone, and a mixture of succinic acid and ethylene glycol and / or butanediol.

  Examples of the lactic acid include L-lactic acid and D-lactic acid; examples of caprolactone include α-caprolactone, β-caprolactone, γ-caprolactone, δ-caprolactone, and ε-caprolactone.

  Examples of the butanediol include 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, and 2,3-butanediol.

  The degradable polyester can be used as a homopolymer obtained by polymerizing these alone or as a copolymer obtained by polymerizing two or more kinds in combination.

  The degradable polyester can be copolymerized with other monomers as long as the effects of the present invention are not impaired.

  Examples of the copolymerizable monomer include hydroxycarboxylic acids such as 3-hydroxybutyric acid, 4-hydroxybutyric acid, 3-hydroxyvaleric acid, 4-hydroxyvaleric acid, and 6-hydroxycaproic acid; ethylene glycol, propylene glycol, Compounds containing multiple hydroxyl groups in the molecule such as butanediol, neopentyl glycol, polyethylene glycol, glycerin, pentaerythritol or their derivatives; succinic acid, adipic acid, sebacic acid, fumaric acid, terephthalic acid, isophthalic acid , 2,6-naphthalenedicarboxylic acid, 5-sodium sulfoisophthalic acid, 5-tetrabutylphosphonium sulfoisophthalic acid-containing compounds containing a plurality of carboxylic acid groups in the molecule, or derivatives thereof.

  The degradable polyester is preferably at least one selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polyethylene succinate, and polybutylene succinate. These degradable polyesters can be used alone or in combination of two or more.

The degradable polyester can be produced according to a known method.
Examples of the method for producing polylactic acid include polycondensation methods in which lactic acid is directly dehydrated under heating and reduced pressure to perform polycondensation, or lactic acid is produced by ring-opening polymerization via lactide which is a cyclic dimer. A ring polymerization method may be mentioned. Such a manufacturing method can be appropriately selected according to the purpose. In addition, a small amount of chain extender, for example, an isocyanate compound, an epoxy compound, an acid anhydride, or an organic peroxide may be used in the polymerization for the purpose of increasing the molecular weight, branching or crosslinking of the degradable polyester. it can.

  The weight average molecular weight and molecular weight distribution of the degradable polyester are not particularly limited as long as they can be substantially molded and exhibit practical mechanical properties. The degradable polyester has a weight average molecular weight of preferably 1 to 1,000,000, more preferably 3 to 700,000, and even more preferably 5 to 500,000. In such a range, the mechanical properties are sufficient, the melt viscosity is suitable, and the molding process is easy.

The degradable polyester may contain one or two or more kinds of polyesters other than those described above (for example, aliphatic polyester and aromatic polyester).
Examples of such aliphatic polyesters include polyethylene adipate, polyethylene sebacate, polybutylene adipate, polybutylene sebacate, polybutylene succinate, polyhexane adipate, and polyhexane sebacate.

  Examples of the aromatic polyester include polyethylene terephthalate and polyethylene isophthalate.

  The purpose of modifying the degradable polyester by copolymerization with other monomers or mixing with aliphatic polyester or aromatic polyester is to reduce crystallinity, melting point, melt fluidity, toughness, Improve impact, flexibility, coefficient of friction, surface roughness, adhesion, mixing, heat resistance and glass transition temperature improvement or reduction, gas barrier properties, moisture permeability, hydrophilic and water repellency improvements, improved degradability Or in suppression. According to such a purpose, a modified polyester suitable for the purpose can be appropriately selected and used in the present invention.

The copolymerization ratio of other monomers is usually less than 50% by mass, preferably 1-30% by mass, and more preferably 2-20% by mass in the total amount of monomers.
As for the mixing ratio of the aliphatic polyester and the aromatic polyester, the aliphatic polyester and / or the aromatic polyester is usually less than 50% by mass, preferably 1 to 30% by mass, and preferably 2 to 20% by mass in the total amount of the polymer. % Is more preferable.

  The shape of the degradable polymer of the present invention is not particularly limited. For example, a pellet shape, a particle shape, a powder shape, a flake shape, and a chip shape are exemplified. Among them, the degradable polymer of the present invention is kneaded with an additive at a temperature lower than its melting temperature, so that the shape thereof is a flake shape or a chip shape that is easily susceptible to deformation even with a low shear force. preferable.

  When a crystalline polylactic acid resin is used as the degradable polymer of the present invention, it is preferably used in a transparent state having a low crystallinity. In order to increase the kneading efficiency and reduce the load on the kneading apparatus, it is most preferable to use a polylactic acid resin that is flat and in an amorphous state.

  There is no particular limitation on the method for processing the degradable polymer of the present invention into such properties. For example, when the crystalline polylactic acid resin is in a cloudy or white pellet state with a high degree of crystallinity, it is first melted with an extruder or the like, and then the discharged molten strand is pushed with a roller or the like in cooling water. There is a method of cooling while crushing and cutting with a normal pelletizer. Further, the degradable polymer of the present invention is in a flat shape and in an amorphous state by being melt-extruded by an extruder having a flat shape such as a rectangular or oblong die hole shape, water-cooled, and pelletized. It can be easily changed into a mode.

  The size after processing of the degradable polymer of the present invention as described above is generally preferably 10 mm or less from the viewpoint of ease of blending and supply.

<Additives>
The additive contained in the biodegradable composition of the present invention is not particularly limited as long as it is solid at room temperature and has a certain degree of rigidity and elasticity, but is preferably a biocompatible compound. . Such an additive is classified into an inorganic substance and an organic substance. As the inorganic substance, for example, a layered silicate is preferable. As the organic substance, for example, a rubbery block copolymer is preferable.

<Inorganic additive (layered silicate)>
The layered silicate will be described below.
The layered silicate is substantially composed of a tetrahedral sheet of silicon oxide and an octahedral sheet of metal hydroxide, and has a property of swelling in water or a dispersion solvent containing water as a main component. There is no particular limitation. Examples include smectite clay minerals, kaolin clay minerals, swellable mica, and vermiculite.

Examples of the smectite clay mineral include montmorillonite, saponite, beidellite, nontronite, hectorite, stevensite, and bentonite.
Examples of kaolin clay minerals include kaolinite, dickite, and halosite.

Examples of the swellable mica include lithium-type teniolite, sodium-type teniolite, lithium-type tetrasilicon mica, and sodium-type tetrafluorosilicon mica.
Vermiculite is classified into trioctahedral vermiculite and dioctahedral vermiculite according to the ion ratio of octahedron.
These layered silicates may be substituted or derivatives thereof. In addition, any of natural, synthetic and processed products can be used. Such layered silicates can be used alone or in combination of two or more.

  Among the layered silicates, the smectite clay mineral is preferable because it easily swells. Among the smectite clay minerals, montmorillonite, bentonite and hectorite are preferable, and montmorillonite and bentonite having sodium ions between layers are more preferable.

  In the present invention, in order to swell the interlayer of the layered silicate to promote delamination and improve the dispersibility in the degradable polymer of the present invention, water or an aqueous solvent is further included in the layered silicate. It is good to use. The amount of water or aqueous solvent necessary for the layered silicate is usually 5% by mass or more, preferably 10% by mass or more. In such a range, the layered silicate is unlikely to peel off when kneaded, and the dispersion into the matrix becomes uniform.

There is no restriction | limiting in particular in the addition method of water or an aqueous solvent. For example, a method of adding a predetermined amount of water or an aqueous solvent dropwise while stirring the layered silicate with a mixer; a method of adding in a mist form using a sprayer; and a method of steaming with steam.
The layered silicate can be added to and stirred in water or an aqueous solvent to form an aqueous solution in which the layered silicate is dispersed in water or an aqueous solvent. In this case, there is no particular limitation on the distributed processing method. For example, an arbitrary method such as a method of adding a layered silicate in water or an aqueous solvent and heating and stirring; ultrasonic treatment; shaking treatment can be used. The solid dispersion concentration of the layered silicate in the aqueous solution can be freely set as long as it is within a concentration range in which the layered silicate can be sufficiently dispersed, but is generally 30% by mass or less, preferably 20% by mass or less. Although a minimum is not specifically limited, 0.05 mass% and also 0.1 mass% are desirable.

  The aqueous solvent is not particularly limited as long as it is a mixed solvent of water and a water-soluble solvent. For example, a mixed solvent of water and a polar solvent can be mentioned. Specific examples of the polar solvent include alcohols such as methanol and ethanol; glycols such as ethylene glycol and propylene glycol; ketones such as acetone and methyl ethyl ketone; ethers such as diethyl ether and tetrahydrofuran. These can be used alone or in combination of two or more.

Furthermore, by adding the following organic compound to the aqueous solvent, the alkali or alkaline earth metal ion of the layered silicate is substituted with this organic compound, and the affinity for the degradable polymer of the present invention is enhanced. You can also.
Examples of the organic compound include onium salts having an onium ion group in the molecule (for example, ammonium salt, sulfonium salt, phosphonium salt). Specific examples of the onium salt include octadecyl ammonium ion, monomethyl octadecyl ammonium ion, dimethyl octadecyl ammonium ion, dodecyl ammonium ion, 6-amino-n-butyric acid ion, 6-amino-n-caproic acid ion, 12 -What has ions, such as an aminododecanoic acid ion, can be illustrated.

  The amount of the layered silicate is a mass proportion of the substantially layered silicate excluding moisture, and is 20% by mass or less in the total amount of the decomposable polymer of the present invention and the layered silicate, and 0.05 to 20 mass% is preferable, 0.05-10 mass% is more preferable, 0.1-5 mass% is further more preferable. In such a range, the biodegradable composition of the present invention has sufficient effects of improving heat resistance and mechanical properties, has good fluidity and does not impair molding processability, and is applied to an apparatus for kneading. This is preferable because the load is reduced and the apparatus is less likely to stop.

<Organic Additive (First Organic Additive)>
The organic additive contained in the biodegradable composition of the present invention has at least one block composed of a vinyl aromatic compound polymer and at least one block composed of a conjugated diene compound polymer. Preferably, a block copolymer in which at least a part of the conjugated diene compound polymer block is saturated by hydrogenation (hereinafter, also referred to as “first organic additive”) can be used.

  As the vinyl aromatic compound which is a constituent unit of the first organic additive, the aromatic part may be monocyclic or polycyclic, for example, styrene, α-methylstyrene, 1-vinylnaphthalene, 2-vinylnaphthalene, 3- One or more of methyl styrene, 4-propyl styrene, 4-cyclohexyl styrene, 4-dodecyl styrene, 2-ethyl-4-benzyl styrene, 4- (phenylbutyl) styrene, and the like can be mentioned. Among these, Styrene and / or α-methylstyrene are preferred.

  Examples of the conjugated diene compound that is a constituent unit of the first organic additive include 1,3-butadiene, 2-methyl-1,3-butadiene (common name, isoprene), 2,3-dimethyl-1,3. -One or more of butadiene, 1,3-pentadiene, 1,3-hexadiene and the like can be mentioned, and among these, 1,3-butadiene, isoprene and combinations thereof are preferable. The microstructure in the block can be arbitrarily selected. For example, in a polybutadiene block, the 1,2-vinyl bond content is preferably 20 to 50% by mass, more preferably 25 to 40% by mass.

  The bonding form of the specific vinyl aromatic compound polymer block and the conjugated diene compound polymer block in the first organic additive is not particularly limited, and is linear, branched, radial, or a combination of two or more thereof. However, among these, a linear bond form is preferable. Examples of rubbery block copolymers include X (YX) m, (XY) n or Y (XY) when the vinyl aromatic compound polymer block is represented by X and the conjugated diene compound polymer block is represented by Y. ) P (where m, n, and p are integers of 1 or more). Among them, a block copolymer in which two or more vinyl aromatic compound polymer blocks X are linearly bonded to one or more conjugated diene compound polymer blocks Y, particularly XYX type It is preferable to use the triblock copolymer.

  In the block Y described above, saturation by hydrogenation of the residual unsaturated bond based on the conjugated diene compound is not particularly necessary, but from the viewpoint of thermal stability during heating and melting, heat resistance of the molded product, and prevention of deterioration of weather resistance. , At least a part of which is hydrogenated is preferable. Preferably, 50% or more, preferably 80% or more of the remaining unsaturated bonds are hydrogenated, and a polymer block mainly composed of a conjugated diene compound is morphologically converted to an olefinic compound polymer block. Can do. Specifically, for example, partially hydrogenated styrene-butadiene block copolymer, partially hydrogenated styrene-isoprene block copolymer, hydrogenated styrene-isoprene block copolymer (SEP, styrene-ethylene-propylene block copolymer). Hydrogenated styrene-butadiene-styrene block copolymer (SEBS, styrene-ethylene-butylene-styrene block copolymer), hydrogenated styrene-isoprene-styrene block copolymer (SEPS, styrene-ethylene-propylene-styrene block copolymer) Copolymer), hydrogenated styrene-butylene-styrene block copolymer (SBS), etc., and among these, block copolymers of linear XYX type bond forms such as SEBS, SEPS, SBS, etc. The coalescence is most preferred. Further, even if the residual unsaturated bond based on a vinyl aromatic compound or a conjugated diene compound is a block copolymer modified with a compound having a functional group such as a hydroxyl group, a carboxyl group, an epoxy group, an amino group or a derivative thereof. Good.

  In this 1st organic additive, content of the structural unit derived from a vinyl aromatic compound is 10-60 mass% with respect to all the structural units (content of the structural unit derived from a conjugated diene is 90-40 mass). %), Preferably 15 to 40% by mass (85 to 60% by mass). If it deviates from this preferred range, the impact resistance of the biodegradable composition of the present invention may be reduced.

  If the number average molecular weight of the first organic additive is too small, the mechanical properties such as strength and elongation at break of the first organic additive itself are lowered, and the strength of the composition may be lowered when a composition is obtained. If the size is too large, the processability is deteriorated and a composition having sufficient performance may not be obtained. Therefore, the number average molecular weight is preferably in the range of 30,000 to 500,000, more preferably. Is in the range of 50,000 to 300,000.

  The first organic additive may be produced by any production method as long as it has the structure described above. The first organic additive may be obtained by using the block copolymer described above. Can be included in one or more.

  In the biodegradable composition of the present invention, the first organic additive is 1 to 100 parts by weight, preferably 1 to 50 parts by weight, more preferably 100 parts by weight of the degradable polymer of the present invention. Contains 2 to 25 parts by weight. If the amount is less than the above range, the resulting biodegradable composition of the present invention has insufficient injection moldability and impact resistance. Conversely, if the amount is too large, the resulting biodegradable composition of the present invention can be obtained. This is not preferable because the material becomes soft and the mechanical strength and heat resistance are lowered.

  The biodegradable composition of the present invention is obtained by graft copolymerizing an epoxy group-containing olefin copolymer and a vinyl (co) polymer in addition to the degradable polymer of the present invention and the first organic additive. A multilayered structure polymer (hereinafter also referred to as “second organic additive”) may be contained.

<Second organic additive>
The epoxy group-containing olefin copolymer constituting the second organic additive is not particularly limited, and a known one can be used. For example, a binary copolymer of an olefin and an unsaturated glycidyl group-containing monomer by high-pressure radical polymerization and a ternary or multi-component copolymer to which another unsaturated monomer is added may be mentioned. In this polymer, ethylene is particularly preferable as the olefin, 60 to 99.5% by mass of ethylene, 0.5 to 40% by mass of glycidyl group-containing monomer, and 0 to 39.5% by mass of other unsaturated monomers. It is preferable that it is the structure. Further, unsaturated glycidyl group-containing monomers include glycidyl acrylate, glycidyl methacrylate, itaconic acid monoglycidyl ester, butenetricarboxylic acid monoglycidyl ester, butenetricarboxylic acid diglycidyl ester, butenetricarboxylic acid triglycidyl ester and α-chloroallyl. Glycidyl esters such as maleic acid, crotonic acid and fumaric acid, or glycidyl ethers such as vinyl glycidyl ether, allyl glycidyl ether, glycidyloxyethyl vinyl ether, styrene-p-glycidyl ether, p-glycidyl styrene, etc. Particularly preferred are glycidyl methacrylate and acryl glycidyl ether. The other unsaturated monomer is at least one monomer selected from olefins, vinyl esters, α, β-ethylenically unsaturated carboxylic acids or derivatives thereof, specifically, propylene, butene- 1, olefins such as hexene-1 and octene-1, vinyl esters such as styrene, vinyl acetate, vinyl propionate and vinyl benzoate, methyl-, ethyl-, propyl of acrylic acid, methacrylic acid, acrylic acid or methacrylic acid -, Butyl-, 2-ethylhexyl-, cyclohexyl-, dodecyl-, octadecyl-, and the like, maleic acid, maleic anhydride, itaconic acid, fumaric acid, maleic acid mono- and di-esters, vinyl chloride, vinylmethyl Vinyl ethers such as ether and vinyl ethyl ether and acrylic amides And acrylates are particularly preferable among them.

  Specific examples of the epoxy group-containing olefin copolymer include ethylene-glycidyl methacrylate copolymer, ethylene-vinyl acetate-glycidyl methacrylate copolymer, ethylene-ethyl acrylate-glycidyl methacrylate copolymer, ethylene- Examples thereof include carbon monoxide-glycidyl methacrylate copolymer, ethylene-glycidyl acrylate copolymer, ethylene-vinyl acetate-glycidyl acrylate copolymer, and the like. Among these, an ethylene-glycidyl methacrylate copolymer is preferable. These are not limited to one type, and two or more types can be mixed and used.

  Examples of other preferable epoxy group-containing olefin copolymers include modified products obtained by adding an unsaturated glycidyl group-containing monomer to a conventional olefin homopolymer or copolymer. Examples of the olefin homopolymer or copolymer in this case include low-density polyethylene, linear low-density polyethylene, high-density polyethylene, polypropylene, polybutene-1, poly-4-methylpentene-1, and other homopolymers, ethylene- Mainly composed of ethylene such as propylene copolymer, ethylene-butene-1 copolymer, ethylene-hexene-1 copolymer, ethylene-4-methylpentene-1 copolymer, ethylene-octene-1 copolymer Copolymers with other α-olefins, copolymers with other α-olefins mainly composed of propylene such as propylene-ethylene block copolymers, ethylene-vinyl acetate copolymers, ethylene-acrylic acid Copolymer, ethylene-methacrylic acid copolymer, ethylene and acrylic acid or methacrylic acid methyl-, ethyl-, Copolymers with esters such as propyl-, isopropyl-, and butyl-, ethylene-maleic acid copolymers, and rubber-like copolymers such as ethylene-propylene copolymer rubber and ethylene-propylene-diene-copolymer rubber Can also be mentioned.

  Specific examples of the vinyl-based (co) polymer that is another component of the second organic additive that can be used in the present invention include styrene, nucleus-substituted styrene, such as methylstyrene, dimethylstyrene, and ethyl. Styrene, isopropyl styrene, chlorostyrene, α-substituted styrene such as vinyl aromatic monomers such as α-methyl styrene and α-ethyl styrene, alkyl esters of 1 to 7 carbon atoms of acrylic acid or methacrylic acid such as (meta ) (Meth) acrylic acid ester monomers such as methyl-, ethyl-, propyl-, isopropyl-, butyl-, etc. of acrylic acid, (meth) acrylonitrile monomers such as acrylonitrile or methacrylonitrile, vinyl acetate, propionic acid Vinyl ester monomers such as vinyl, acrylamide, methacrylamide, etc. (Meth) acrylamide monomers, (meth) acrylic acid, maleic acid, fumaric acid, itaconic acid, citraconic acid, crotonic acid and other unsaturated carboxylic acids and their amides, imides, esters, anhydrides and other vinyl derivatives It is a (co) polymer obtained by polymerizing one or more of the monomers. Among these, vinyl aromatic monomers, (meth) acrylic acid ester monomers, (meth) acrylonitrile monomers and vinyl ester monomers are preferably used. In the present invention, a vinyl aromatic monomer is most preferably used, and its number average molecular weight is 10 to 15000, preferably 50 to 10,000. When the number average molecular weight is too small, the heat resistance of the biodegradable composition of the present invention is lowered, and when the number average molecular weight is too large, the moldability tends to be lowered, which is not preferable.

  As the grafting method for producing the second organic additive, any of well-known methods such as chain transfer method and ionizing radiation irradiation method can be used. For example, Japanese Patent Publication No. 6-51767 is available. It is preferable to use the production method described in Japanese Patent Publication No. 6-102702. That is, 100 parts by mass of an epoxy group-containing olefin copolymer is suspended in water, and a specific radical polymerizable organic peroxide is separately added to 5 to 400 parts by mass of the vinyl monomer to 100 parts by mass. The radical (co) polymerization initiator having a decomposition temperature of 40 to 90 ° C. for obtaining a 10-hour half-life of 0.1 to 10 parts by mass with respect to parts by weight of vinyl monomer and radical-polymerizable organic solvent. A solution in which 0.01 to 5 parts by mass is dissolved with respect to 100 parts by mass in total with the oxide is added, and the mixture is heated under conditions where decomposition of the radical polymerization initiator does not substantially occur. An epoxy group-containing olefin copolymer is impregnated with a polymerizable organic peroxide and a radical polymerization initiator, and when the impregnation rate reaches 50% by mass or more, the temperature of the aqueous suspension is increased, By copolymerizing a monomer and a radical polymerizable organic peroxide in an epoxy group-containing olefin copolymer, a grafted precursor is obtained, and this grafted precursor is melt-kneaded at 100 to 300 ° C. This is a method for obtaining a second organic additive that can be used in the present invention. According to this method, since the graft efficiency is high and secondary aggregation due to heat does not occur, the development of performance becomes more effective.

  In the second organic additive, the content of the structural unit derived from the epoxy group-containing olefin copolymer relative to all the structural units is not limited, but the structural unit derived from the epoxy group-containing olefin copolymer is 10 to 90. The structural unit derived from the vinyl (co) polymer is 90 to 10% by mass, preferably 80 to 20% by mass, preferably 20 to 80% by mass. If the content (% by mass) of the structural unit derived from the epoxy group-containing olefin copolymer is too small relative to the total structural unit, the effect of thickening the melt viscosity of the biodegradable composition of the present invention is insufficient. On the other hand, if it is too large, the affinity with the first organic additive is lowered, and a gelled product is likely to be formed.

  In the biodegradable composition of the present invention, the second organic additive is 1 to 50 parts by mass, preferably 1 to 20 parts by mass, more preferably 100 parts by mass of the degradable polymer of the present invention. It can contain 1-10 mass parts. This second organic additive can be optionally used for the biodegradable composition of the present invention, but there is no particular problem regarding injection moldability even if it is not used. However, it is preferable to use the second organic additive in such a range because good impact resistance is required. Moreover, when there are too many compounding quantities of a 2nd organic additive, since a composition will soften and mechanical strength and heat resistance will fall, it is unpreferable.

  The biodegradable composition of the present invention includes a polyolefin resin (hereinafter referred to as “third organic additive”) in addition to the degradable polymer of the present invention, the first organic additive, and the second organic additive. May also be included).

<Third organic additive>
The polyolefin-based resin that is the third organic additive that can be used in the present invention is obtained by amplifying the melt viscosity of the biodegradable composition of the present invention and the second organic additive into the degradable polymer of the present invention. It is a necessary component as an intermediary substance to be dispersed, and there are no particular limitations on its production method and physical properties. Α such as ethylene, propylene, butene-1,3-methylbutene-1,4-methylpentene-1, octene-1, etc. -Use of homopolymers of olefins, copolymers thereof, polyolefins modified with unsaturated organic carboxylic acids or derivatives thereof, or copolymers of these with other copolymerizable unsaturated monomers, etc. be able to. Specific examples include polyethylene such as low density polyethylene (LDPE), medium density or high density polyethylene (HDPE), linear low density polyethylene (LLDPE), ethylene-vinyl acetate copolymer, ethylene-ethyl acrylate copolymer. Resin, polypropylene homopolymer, polypropylene modified with unsaturated organic carboxylic acid such as maleic acid or derivatives thereof, propylene-ethylene block copolymer or random copolymer, propylene-ethylene-butene-1 copolymer, etc. Polypropylene resin, polybutene-1, polypentene-1, poly-4-methylpentene-1, and the like. These can be used alone or in combination of two or more. In the present invention, among these, polyethylene resins such as HDPE and LLDPE can be preferably used. The polyethylene-based resin is not particularly limited, and those having a wide range of molecular weights can be used. From the viewpoint of the extrusion melt viscosity of the biodegradable composition of the present invention, 190 ° C. and 2. The melt flow rate (MFR) at a load of 16 kgf is preferably 0.01 to 10 g / 10 min, more preferably 0.01 to 5 g / 10 min. Furthermore, a pulverized product such as a molded product of the polyethylene resin and molding waste, or a repellet obtained by melt-kneading them can be suitably used. The polyolefin resin as the third organic additive includes ethylene-α-olefin copolymer rubber, ethylene-α-olefin-nonconjugated diene compound copolymer rubber (for example, EPDM), ethylene-aromatic. You may contain rubbers, such as a monovinyl compound-conjugated diene type compound copolymer rubber, and these hydrogenated substances.

  The polyolefin resin as the third organic additive can be blended in an amount of 3 to 60 parts by mass, preferably 5 to 50 parts by mass, with respect to 100 parts by mass of the degradable polymer of the present invention. If the blending amount of the third organic additive is too small, the melt viscosity is low and it is easy to draw down, which is not preferable because the extrusion moldability is impaired. On the other hand, when the amount is too large, mechanical strength such as bending strength and elastic modulus of the biodegradable composition of the present invention to be obtained is not preferable.

  The biodegradable composition of the present invention includes, in addition to the degradable polymer of the present invention and the first organic additive, a polycarbonate resin (hereinafter also referred to as “fourth organic additive”) and isocyanate. A system compound (hereinafter also referred to as “fifth organic additive”) may be contained.

<4th organic additive>
Specific examples of the polycarbonate-based resin that is the fourth organic additive include aromatic polycarbonates obtained by reacting a dihydric phenol and a carbonate precursor. This production method is known per se, a method in which a carbonate precursor such as phosgene is directly reacted with a dihydric phenol (interfacial polymerization method), or a transesterification reaction between a dihydric phenol and a carbonate precursor such as diphenyl carbonate in a molten state. A method (solution method) is known.

  Dihydric phenols include hydroquinone, resorcin, dihydroxydiphenyl, bis (hydroxyphenyl) alkane, bis (hydroxyphenyl) cycloalkane, bis (hydroxyphenyl) sulfide, bis (hydroxyphenyl) ether, bis (hydroxyphenyl) ketone, bis (Hydroxyphenyl) sulfone, bis (hydroxyphenyl) sulfoxide, bis (hydroxyphenyl) benzene, and derivatives thereof in which the nucleus is substituted with an alkyl group or a halogen atom. Representative examples of particularly suitable dihydric phenols include 2,2-bis (4-hydroxyphenyl) propane (commonly called bisphenol A), 2,2-bis {(4-hydroxy-3-methyl) phenyl} propane, , 2-bis {(3,5-dibromo-4-hydroxy) phenyl} propane, 2,2-bis (4-hydroxyphenyl) butane, 1,1-bis (4-hydroxyphenyl) cyclohexane, 1,1- Bis (4-hydroxyphenyl) -3,3,5-trimethylcyclohexane, 4,4'-dihydroxydiphenylsulfone, bis {(3,5-dimethyl-4-hydroxy) phenyl} sulfone, etc. Or more can be mixed. Of these, the use of bisphenol A is particularly preferred.

  Examples of the carbonate precursor include diaryl carbonates such as diphenyl carbonate, ditoluyl carbonate and bis (chlorophenyl) carbonate, dialkyl carbonates such as dimethyl carbonate and diethyl carbonate, carbonyl halides such as phosgene, and haloformates such as dihaloformates of dihydric phenols. However, it is not limited to these. Preferably, diphenyl carbonate is used. These carbonate precursors may also be used alone or in combination of two or more.

  The fourth organic additive that can be used in the present invention is, for example, 1,1,1-tris (4-hydroxyphenyl) ethane or 1,1,1-tris (3,5-dimethyl-4-hydroxyphenyl). It may be a branched polycarbonate resin copolymerized with a trifunctional or higher polyfunctional aromatic compound such as ethane, or a polyester carbonate resin copolymerized with an aromatic or aliphatic difunctional carboxylic acid. Moreover, the mixture which mixed 2 or more types of the obtained polycarbonate resin may be sufficient.

The molecular weight of the polycarbonate resin is usually about 1 × 10 ⁴ to 1 × 10 ^{5 in} terms of viscosity average molecular weight, but the molecular weight of the polycarbonate resin which is the fourth organic additive used in the present invention is about 12,000 to 30,000. 13,000 to 25,000 is more preferable.

<Fifth organic additive>
The isocyanate compound as the fifth organic additive is not particularly limited, but a polyisocyanate compound having at least two isocyanate groups in the molecule can be preferably used. This includes polyisocyanate-modified compounds obtained by reacting polyisocyanate compounds with polyols, polyester-based or polycarbonate-based diols, and the like. Examples of such polyisocyanate compounds include 2,4-tolylene diisocyanate, 2,6-tolylene diisocyanate, 2,4'-diphenylmethane diisocyanate, 4,4'-diphenylmethane diisocyanate, 1,5-naphthylene diisocyanate, m-xylene diisocyanate, p-xylene diisocyanate, m-trimethylxylene diisocyanate, m-tetramethylxylene diisocyanate, bis- (4,4'-isocyanatophenyl) methane, naphthalene diisocyanate, triphenylmethane triisocyanate, polymethylene polyphenyl Aromatic polyisocyanates having a backbone of tolylene such as polyisocyanate, diphenylmethane, naphthylene, tolidine, xylene, triphenylmethane, etc. Isophorone such as cyclohexane diisocyanate, isophorone diisocyanate, hydrogenated 4,4′-diphenylmethane diisocyanate, bis (4,4′-isocyanatocyclohexyl) propane, 1,3-bis (isocyanatomethyl) cyclohexane, norbornane diisocyanate methyl, Hexamethylene such as alicyclic polyisocyanate having skeleton of hydrogenated diphenylmethane, 1,6-hexamethylene diisocyanate, 1,4-tetramethylene diisocyanate, 2,2,4-trimethylhexamethylene diisocyanate, lysine diisocyanate, etc. Aliphatic polyisocyanates having a lysine or the like as a skeleton can be mentioned, and any of these can be used, and one or more can be mixed and used. Among these, since the biodegradable composition of the present invention that is tougher and excellent in stretchability and deep drawability can be obtained, an isocyanate group such as triphenylmethane triisocyanate, polymethylene polyphenyl polyisocyanate, etc. Are preferably used, or a mixture of these and the diisocyanate.

  Further, as the polyisocyanate having 3 or more isocyanate groups, isocyanurate-modified products, particularly isocyanurate ring-containing triisocyanates can also be preferably used. Specific examples include isocyanurate-modified hexamethylene diisocyanate, isocyanurate-modified isophorone diisocyanate, isocyanurate-modified tolylene diisocyanate, and the like.

  The biodegradable composition of the present invention can contain the fourth and fifth organic additives in addition to the degradable polymer of the present invention and the first organic additive. The composition ratio in the biodegradable composition of the invention is such that when only the degradable polymer of the present invention and the first organic additive are contained, when the second organic additive is further contained, the third organic It differs from the case of containing an additive.

  When the biodegradable composition of the present invention contains the fourth and fifth organic additives, the degradable polymer of the present invention is 50 to 90 parts by mass and the fourth organic additive is 50 to 10 parts by mass. 5-100 mass parts of 1st organic additives and 0.1-5 mass parts of 5th organic additives are contained with respect to a total of 100 mass parts.

  Here, the ratio (polymer / fourth) of the degradable polymer and the fourth organic additive of the present invention is 50 to 90/50 to 10 as described above, but 60 to 80/40. It is preferably ~ 20. If the amount of the degradable polymer of the present invention is too small, the shape decomposability, rolling, stretching and deep drawability of the biodegradable composition of the present invention are deteriorated, and chemical resistance is also impaired. On the other hand, if the amount of the degradable polymer of the present invention is too large, the impact resistance and heat resistance of the biodegradable composition of the present invention are lowered and the molded product is likely to warp, which is not preferable.

  The biodegradable composition of the present invention contains 5 to 100 parts by mass of the first organic additive with respect to 100 parts by mass in total of the degradable polymer of the present invention and the fourth organic additive. It is preferable to contain 7-60 mass parts, and it is more preferable to contain 10-45 mass parts. If the first organic additive is too small, the impact resistance of the biodegradable composition of the present invention is not sufficient, and conversely if too large, the biodegradable composition of the present invention becomes soft and mechanical strength is increased. , Heat resistance decreases.

  Furthermore, the biodegradable composition of the present invention contains 0.1 to 5 parts by mass of the fifth organic additive with respect to 100 parts by mass in total of the degradable polymer of the present invention and the fourth organic additive. However, it is preferable to contain 0.3-3 mass parts. If the fifth organic additive is too small, the impact resistance of the biodegradable composition of the present invention is impaired, and conversely if too large, the degradable polymer and / or the first organic additive has a hydroxyl group. It is not preferable because molecular chain extension and cross-linking due to reaction with the compound etc. proceed excessively to cause a significant thickening phenomenon and a large amount of gelled product. When the fifth organic additive is contained in such a range, a network by appropriate crosslinking is formed, the compensation effect of hydrolysis and thermal decomposition, the degradable polymer of the present invention, and the fourth organic additive It is considered that the compatibility effect is well balanced and contributes to the improvement of the rollability, stretchability, deep drawability and impact resistance.

  The biodegradable composition of the present invention contains the degradable polymer of the present invention and the above-mentioned additives (layered silicate, first organic additive, etc.), and further includes a thermoplastic elastomer; a thermosetting elastomer. A rubbery polymer such as butadiene rubber, styrene-butadiene copolymer rubber, acrylonitrile-butadiene copolymer rubber or hydrogenated nitrile rubber may be contained. These content rates are 20 mass% or less as a content rate with respect to the whole biodegradable composition of this invention, Preferably it is 15 mass% or less, More preferably, it is 10 mass% or less.

  Here, as the thermoplastic elastomer, specifically, polystyrene (for example, styrene-butadiene-styrene block copolymer, styrene-isoprene-styrene block copolymer, styrene-ethylenebutylene-styrene block copolymer), Examples include polyolefin, polyurethane, polyester, polyamide, 1,2-polybutadiene, polyvinyl chloride, and elastomers in which rubber is dispersed.

  Specific examples of thermosetting elastomers include urethane, silicone, modified silicone, polysulfide, and modified epoxy.

  Specific examples of the butadiene rubber include high cis-butadiene rubber and low cis-butadiene rubber.

  Specific examples of the styrene-butadiene copolymer rubber include emulsion-polymerized styrene-butadiene rubber and solution-polymerized styrene-butadiene rubber.

<Optional component>
The biodegradable composition of the present invention may contain an optional component in addition to the degradable polymer of the present invention and the additive, for example, a pigment that does not harm the living body. , Dye, reinforcing agent (glass fiber, carbon fiber, talc, mica, viscosity favorite, potassium titanate fiber, etc.), filler (carbon black, silica, alumina, titanium oxide, metal powder, wood powder, rice husk, etc.), heat resistant It may contain a stabilizer, an oxidative degradation inhibitor, an ultraviolet absorber, a lubricant, a mold release agent, a crystal nucleating agent, a plasticizer, a flame retardant, an antistatic agent, a foaming agent and the like. These are contained within a range that does not inhibit the effects of the present invention, for example, 20% by mass or less, preferably 15% by mass or less, and more preferably 10% by mass or less as the total content of the biodegradable composition of the present invention. May be.
Among these, the biodegradable composition of the present invention contains 1 to 20 parts by mass of carbon fiber with respect to 100 parts by mass of the total amount of the degradable polymer of the present invention and the first organic additive. Then, it is possible to manufacture a stent that is high in strength, excellent in flexibility, and excellent in in-vivo safety (biocompatibility).

<Method for producing biodegradable composition>
The manufacturing method of the biodegradable composition of this invention is demonstrated below.
The biodegradable composition of the present invention is obtained by kneading the degradable polymer of the present invention and the additive at a temperature of 0 ° C. or higher and lower than the melting temperature of the degradable polymer of the present invention. Are preferably manufactured.
However, when the first, second and third organic additives are used as the additive, the melting point of the third organic additive is not lower than the melting point of the decomposable polymer of the present invention. It is preferable to knead at the temperature.

The kneading apparatus for producing the biodegradable composition of the present invention is not particularly limited as long as the above components can be shear kneaded. For example, an extruder, a Banbury mixer, a roller, and a kneader can be mentioned.
Examples of the extruder include a screw extruder such as a single-screw extruder and a twin-screw extruder, an elastic extruder, a hydrodynamic extruder, a ram-type continuous extruder, a roll-type extruder, a gear-type extruder, and the like. be able to. Among these, a screw extruder, particularly a twin screw extruder is preferable, and a twin screw extruder having one or more vents (deaeration ports) with good deaeration efficiency is more preferable. The mixing order of the components is not particularly limited.

The temperature at which the biodegradable composition of the present invention is kneaded using the kneading apparatus is preferably 0 ° C. or more and lower than the melting temperature of the degradable polymer of the present invention (such as The kneading in the temperature range is hereinafter also referred to as “low temperature kneading”). More preferably, it is above the glass transition temperature of the degradable polymer of the present invention and below the melting temperature. When the kneading temperature is in such a range, the load on the kneading apparatus can be reduced by softening the degradable polymer of the present invention, which is preferable.
Here, the melting temperature refers to the end point temperature of the crystal melting endothermic peak that appears during temperature rise measurement by a differential scanning calorimeter (DSC). Moreover, a glass transition point means the transition temperature calculated | required from the thermograph in the measurement by the differential scanning calorimeter based on JIS-K7121.

The degradable polymer and / or the additive of the present invention can be pre-dried before kneading. When such preliminary drying is sufficiently performed, it can be obtained by ordinary melt kneading.
In addition, since the isocyanate compound is highly reactive, it reacts sufficiently even at low temperature kneading and does not impair the characteristics of the biodegradable composition of the present invention used.

  In general, polyesters and polycarbonate resins are commercially available in the form of pellets. From these virgin pellets, these are pressed at a temperature equal to or higher than the glass transition temperature, or once melted with an extruder or the like, and the molten strand is crushed through a roller in cooling water and cut with a normal pelletizer, A flat flake-like form suitable for low-temperature kneading can be obtained.

When kneading at low temperature using a twin screw extruder, the biodegradable composition of the present invention is discharged from an unmelted state to a semi-molten state at a temperature lower than the melting temperature of the degradable polymer of the present invention. Sometimes. In such a case, extrusion can be performed with the die head open. When the die head is opened, it can be changed into particles that can be easily formed by passing the discharged material through a pulverizer. For example, by installing a pulverizer directly below the discharge port at the tip of the extruder, it is possible to continuously perform the fragmentation treatment.
Even when the die head is closed, the kneaded material can be temporarily melted and drawn as a strand by setting the die head in the vicinity of the melting point of the polyester resin, and this can be pelletized by a known method. Can do.

When manufactured by such a method, a biodegradable composition having a Young's modulus by a tensile test of 100 MPa or more, an elongation at a yield point of 20% or less, and an elongation at a break point of 40% or more can be obtained. it can.
When the biodegradable composition of the present invention is produced by kneading at a temperature higher than the melting temperature of the degradable polymer of the present invention, the Young's modulus by a tensile test is 100 MPa or more, and the elongation at the yield point is 20 % Or less, and it is not preferable for obtaining the biodegradable composition of the present invention having the property that the elongation at break is 40% or more.
Further, kneading at a temperature lower than 0 ° C. is not preferable because an excessive load is applied to the kneading apparatus and the apparatus may be stopped or broken.

The physical properties of the biodegradable composition of the present invention will be described below.
The biodegradable composition of the present invention is a composition having a Young's modulus by a tensile test of 100 MPa or more, an elongation at a yield point of 20% or less, and an elongation at a break point of 40% or more.

  Here, the tensile test is measured by the method defined in JIS-K7113. Here, the test piece was a press molding machine, preheated for 2 to 10 minutes at a temperature 10 to 30 ° C. higher than the melting temperature of the degradable polymer of the present invention, and then the pressure was 20 MPa and the decomposable polymer of the present invention was melted. A No. 2 test piece prepared by pressing for 1 to 5 minutes at a temperature 10 to 30 ° C. higher than the temperature is used. This test piece is used for a tensile test after conditioning for 48 hours at 25 ° C. and 50% relative humidity.

  The tensile test is performed under the conditions of 25 ° C. and relative humidity of 50%, and the tensile speed is 100 mm / min.

  Further, the Young's modulus is preferably 100 to 3000 MPa, and more preferably 500 to 1000 MPa.

  Further, the elongation at the yield point is preferably 2 to 20%, and more preferably 5 to 15%.

  Further, the elongation at the breaking point is preferably 40 to 2500%, and more preferably 50 to 500%.

  If the biodegradable composition of the present invention on the surface of the stent body of the present invention has such Young's modulus, elongation at the yield point, and elongation at the break point, plastic deformability under an environment of about room temperature. Therefore, the biodegradable composition of the present invention on the surface of the stent is not destroyed by expansion during use, and the biological and physiologically active substance of the present invention has a desired speed from the surface of the stent body of the present invention. Released at. In addition, when the stent of the present invention is attached to the balloon, sufficient caulking operation of the stent of the present invention to the balloon can be performed, and there is no concern about a decrease in the gripping force of the stent of the present invention on the balloon and further the dropping of the stent. .

  In the biodegradable composition of the present invention, the absolute value of the difference between the yield point stress and the break point stress by the tensile test is preferably 30% or less of the yield point stress, and 20% or less. More preferably, it is 10% or less. If it is such a range, it is preferable at the point which is more excellent in plastic deformability.

<Stent body>
The stent body of the present invention may be formed using the above-described biodegradable composition of the present invention, and other compositions that do not degrade in vivo (hereinafter referred to as “the non-biodegradable composition of the present invention”). May also be formed using a metal material, ceramics, or the like.
If the stent main body of the present invention is formed using the biodegradable composition of the present invention, the entire stent of the present invention is decomposed in vivo after a lapse of a certain period of time. There is an effect that it is possible to prevent an adverse effect on the living body due to the presence of, without re-operation. Further, when used as a balloon expandable stent, it is excellent in flexibility and plastically deforms at room temperature, so that it expands easily and hardly recoils after balloon expansion.

<Stent body made of non-degradable composition in vivo>
The stent body of the present invention may be formed from the in vivo non-degradable composition of the present invention. In this case, since it does not decompose in the living body, it can be left at the target site for a long period (semi-permanent if necessary). When used as a balloon-expandable stent, the stent body of the present invention is excellent in flexibility and plastically deforms at room temperature, so that it expands easily and hardly recoils after balloon expansion.

<Non-biodegradable composition>
The in-vivo non-degradable composition of the present invention comprises a polymer that is solid at room temperature and does not degrade in vivo (hereinafter also referred to as “the non-degradable polymer of the present invention”) and the in-vivo of the present invention. It consists of the same additive as that used in the degradable composition.

<Non-degradable polymer>
The non-degradable polymer of the present invention is not particularly limited as long as it is solid at room temperature, does not decompose in vivo, and has a certain degree of rigidity and elasticity, but a non-degradable polyester resin is preferable, Furthermore, what has biocompatibility is still more preferable.
This non-degradable polyester resin is not particularly limited, and can be obtained by polycondensing a dicarboxylic acid unit or a derivative thereof having an ester-forming ability, a diol unit or an ester-forming ability thereof by a known method. It is a polyester resin.

  Examples of dicarboxylic acid units include terephthalic acid, isophthalic acid, orthophthalic acid, 2,2'-biphenyldicarboxylic acid, 3,3'-biphenyldicarboxylic acid, 4,4'-biphenyldicarboxylic acid, 4,4'-diphenylether Aromatics such as dicarboxylic acid, 1,5-naphthalenedicarboxylic acid, 1,4-naphthalenedicarboxylic acid, 2,6-naphthalenedicarboxylic acid, bis (p-carboxyphenyl) methane, anthracene dicarboxylic acid, sodium 5-sulfoisophthalate Aliphatic dicarboxylic acids such as dicarboxylic acid, adipic acid, sebacic acid, succinic acid, azelaic acid, malonic acid, succinic acid, dodecanedioic acid, alicyclic such as 1,3-cyclohexanedicarboxylic acid, 1,4-cyclohexanedicarboxylic acid Dicarboxylic acids and their ester-forming derivatives ( Example, if methyl esters, lower alkyl esters such as ethyl ester, etc.) can be mentioned dicarboxylic acid units derived from such.

  Examples of the diol unit include ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,3-propanediol, 1,4-butanediol, 2,3-butanediol, 1,6 -C2-C10 aliphatic diols such as hexanediol, 1,10-decanediol, neopentyl glycol, 2-methylpropanediol, 1,5-pentadiol, 1,4-cyclohexanedimethanol, 1,4 -A diol component derived from a polyalkylene glycol having a molecular weight of 6000 or less, such as cycloaliphatic diol such as cyclohexanediol, diethylene glycol, polyethylene glycol, poly-1,3-propylene glycol, polytetramethylene glycol, etc. .

  Both of these dicarboxylic acid units and diol units may be used alone or in combination of two or more. Furthermore, if the non-degradable polyester resin of the present invention is 1 mol% or less based on the total structural unit, for example, trifunctional or higher functional groups such as glycerin, trimethylolpropane, pentaerythritol, trimellitic acid, and pyromellitic acid. It may have a structural component derived from a monomer.

  Specific examples of such non-degradable polyester resins include, for example, polyethylene terephthalate, polybutylene terephthalate (hereinafter sometimes referred to as PBT), polypropylene terephthalate, polyethylene naphthalate, polybutylene naphthalate, poly-1, Examples include 4-cyclohexanedimethylene terephthalate, polycaprolactone, p-hydroxybenzoic acid polyester, and polyarylate resin. Among these, polyethylene terephthalate using ethylene glycol as the diol component is particularly preferable from the viewpoint of the balance of physical properties such as crystallization behavior, thermal properties and mechanical properties, and polybutylene using butylene glycol as the diol component. The terephthalate is also preferable in terms of balance of moldability, mechanical properties, etc., and a mixture of this and the above-mentioned polyethylene terephthalate can also be suitably used. Furthermore, polyethylene naphthalate or a mixture of this with polyethylene terephthalate (preferably a mixture containing 50% by mass or more of PET) is also preferable.

  Although there is no restriction | limiting in particular in the intrinsic viscosity of the said nondegradable polyester-type resin, In this invention, Preferably it is 0.60-1.20 dl / g, More preferably, it is the range of 0.65-1.10 dl / g. . If the intrinsic viscosity is too small, sufficient impact resistance and stretchability cannot be obtained, and chemical resistance may be lowered. On the other hand, if the intrinsic viscosity is too large, the rollability at room temperature may decrease with an increase in the fluid viscosity. Here, the intrinsic viscosity is a value when measured at 30 ° C. using a mixed solvent of phenol / tetrachloroethane (weight ratio: 1/1).

  In the present invention, the shape, processing method, and size of the non-degradable polymer of the present invention are the same as those of the degradable polymer of the present invention.

  The additive used for the biodegradable composition of the present invention is the same as the additive used for the biodegradable composition of the present invention. The additive content in the non-biodegradable composition of the present invention, optional components, production method, properties of the produced composition, etc. are all the same as in the biodegradable composition of the present invention described above. It is.

<Stent body made of metal or ceramics>
In addition, the stent body of the present invention may be formed of a material having a strength that can withstand an expansion operation when placed in a lumen, and for example, a metal material or ceramics can be used. In particular, when a metal material is used, the strength is excellent, and therefore, the stent of the present invention can be reliably placed at a target site in a living body, which is preferable.

  Examples of such a metal material include stainless steel, Ni—Ti alloy, tantalum, nickel, chromium, iridium, tungsten, cobalt-based alloy, and the like. Of stainless steel, SUS316L, which has the best corrosion resistance, is suitable.

  Many of the stent bodies of the present invention formed of such metal materials can be expanded using a balloon. In addition, for example, a metal material having a property called pseudoelasticity, in which the strain greatly changes at a constant stress, such as a Ni-Ti alloy, or a property in which the strain gradually increases and changes as the stress increases. If the stent body is formed, a self-expanding stent can be manufactured. In this case, the stent body of the present invention that has been compressed and held in advance is expanded by the elastic force by releasing the compression at the lesion.

  The shape of the stent body of the present invention is not particularly limited as long as it has sufficient strength to be stably placed in a lumen in a living body. For example, a metal material wire or a polymer material fiber knitted into a cylindrical shape, or a tubular body made of a metal material or ceramics with pores is preferably mentioned.

  The stent body of the present invention may be either a balloon expansion type or a self-expansion type. Further, the size of the stent body of the present invention may be appropriately selected according to the application location.

<Stent body manufacturing method>
The manufacturing method in the case of manufacturing the stent body of the present invention using the biodegradable composition of the present invention or the non-biodegradable composition of the present invention is the same, and known methods such as injection molding, It can be produced by a method such as extrusion molding, press molding, vacuum molding or blow molding. Details are illustrated below.

  First, the biodegradable composition of the present invention or the non-biodegradable composition of the present invention produced by the above method is molded into a pipe having a predetermined thickness and outer shape using an extruder. And an opening pattern is affixed on the pipe surface, and pipe parts other than this opening pattern are melt | dissolved by etching techniques, such as laser etching and chemical etching, and an opening part is formed. Alternatively, the opening can be formed by cutting the pipe according to the pattern by a laser cutting technique based on the pattern information stored in the computer.

  In addition, for example, in the case of a coiled stent, the biodegradable composition of the present invention or the non-biodegradable composition of the present invention is formed into a wire having a predetermined thickness and shape using an extruder. . Then, after the wire is bent to form a wave pattern or the like, the wire is spirally wound on the mandrel, and then the mandrel is extracted and the shaped wire is cut into a predetermined length. .

Moreover, also when manufacturing the stent main body of this invention using a metal, it can manufacture by a normal method. For example, the following methods can be mentioned.
First, a metal material is dissolved in an inert gas or a vacuum atmosphere.
Next, it is cooled to form an ingot, the ingot is mechanically polished, and then hot-pressed and extruded to obtain a large-diameter pipe. Then, the diameter of the pipe is reduced to a predetermined thickness and outer shape by sequentially repeating the die drawing process and the heat treatment process. And an opening pattern is affixed on the pipe surface, and pipe parts other than this opening pattern are melt | dissolved by etching techniques, such as laser etching and chemical etching, and an opening part is formed. Alternatively, the opening can be formed by cutting the pipe according to the pattern by a laser cutting technique based on the pattern information stored in the computer.
By such a method, the stent body of the present invention made of metal can be manufactured.

<Biologically bioactive substances>
The stent of the present invention has the biological physiologically active substance of the present invention on the surface of the stent body of the present invention.
The biological and physiologically active substance of the present invention is not particularly limited as long as it suppresses stenosis and occlusion of the vascular system that can occur when the stent of the present invention is placed in a lesion, and can be arbitrarily selected. For example, anticancer agents, immunosuppressive agents, antibiotics, antirheumatic agents, antithrombotic agents, HMG-CoA reductase inhibitors, ACE inhibitors, calcium antagonists, antihyperlipidemic agents, integrin inhibitors, anti From allergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, anti-inflammatory drugs, bio-derived materials, interferons, NO production promoters At least one selected from the group is preferable in that the lesion can be treated by controlling the behavior of cells in the lesion tissue.

  Preferred examples of the anticancer agent include vincristine, vinblastine, vindesine, irinotecan, pirarubicin, paclitaxel, docetaxel, and methotrexate.

  Preferred examples of the immunosuppressant include sirolimus, tacrolimus, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, everolimus, ABT-578, AP23573, CCI-779, gusperimus, and mizoribine.

  As the antibiotic, for example, mitomycin, adriamycin, doxorubicin, actinomycin, daunorubicin, idarubicin, pirarubicin, aclarubicin, epirubicin, pepromycin, dinostatin styramer and the like are preferable.

  As the anti-rheumatic agent, for example, methotrexate, sodium thiomalate, penicillamine, lobenzalit and the like are preferable.

  As the antithrombotic agent, for example, heparin, aspirin, antithrombin preparation, ticlopidine, hirudin and the like are preferable.

  Preferred examples of the HMG-CoA reductase inhibitor include cerivastatin, cerivastatin sodium, atorvastatin, rosuvastatin, pitavastatin, fluvastatin, fluvastatin sodium, simvastatin, lovastatin, pravastatin and the like.

  As the ACE inhibitor, for example, quinapril, perindopril erbumine, trandolapril, cilazapril, temocapril, delapril, enalapril maleate, lisinopril, captopril and the like are preferable.

  As the calcium antagonist, for example, hifedipine, nilvadipine, diltiazem, benidipine, nisoldipine and the like are preferable.

  As the antihyperlipidemic agent, for example, probucol is preferable.

  As the integrin inhibitor, for example, AJM300 is preferable.

  As the antiallergic agent, for example, tranilast is preferable.

  As said antioxidant, (alpha) -tocopherol is preferable, for example.

  As the GPIIbIIIa antagonist, for example, abciximab is preferable.

  As the retinoid, for example, all-trans retinoic acid is preferable.

  As the flavonoid, for example, epigallocatechin, anthocyanin, and proanthocyanidin are preferable.

  As the carotenoid, for example, β-carotene and lycopene are preferable.

  As the lipid improving agent, for example, eicosapentaenoic acid is preferable.

  As the DNA synthesis inhibitor, for example, 5-FU is preferable.

  As the tyrosine kinase inhibitor, for example, genistein, tyrphostin, arbustatin, staurosporine and the like are preferable.

  As the antiplatelet drug, for example, ticlopidine, cilostazol, and clopidogrel are preferable.

  As the anti-inflammatory drug, for example, steroids such as dexamethasone and prednisolone are preferable.

  Examples of the bio-derived material include EGF (epidemal growth factor), VEGF (basic endowment growth factor), HGF (hepatocyte growth factor), PDGF (platelet growth factor), and PDGF (platelet growth factor).

  As the interferon, for example, interferon-γ1a is preferable.

  As the NO production promoting substance, for example, L-arginine is preferable.

  Whether these biological physiologically active substances are to be one kind of biological physiologically active substance or to combine two or more different biological physiologically active substances may be appropriately selected according to the case. .

  The stent of the present invention preferably has a layer comprising the biological physiologically active substance of the present invention and the biodegradable composition of the present invention on the surface of the stent body of the present invention. The reason is that as the biodegradable composition of the present invention degrades, the biological and physiologically active substance of the present invention is gradually released into the living body to enable appropriate treatment.

  Here, the composition ratio (mass ratio) between the biological physiologically active substance of the present invention and the biodegradable composition of the present invention is 1:99 to 99: 1, more preferably 30:70 to 70:30. . The reason is that as much of the biologically physiologically active substance of the present invention as possible can be loaded while taking into consideration the physical properties and degradability of the biodegradable composition of the present invention.

In such a ratio, the biological physiologically active substance of the present invention and the biodegradable composition of the present invention are mixed in a solvent such as acetone, ethanol, chloroform, tetrahydrofuran, etc., with a solution concentration of 0.001 to 20% by mass, Preferably, it is dissolved so as to be 0.01 to 10% by mass to produce a solution.
Using such a solution, a layer is formed on the surface of the stent body of the present invention by the method described later. Here, the layer thickness (average thickness) is 1 to 100 μm, preferably 1 to 50 μm, and more preferably 1 to 10 μm. If the layer has a thickness within this range, it can be easily inserted into a lumen such as a blood vessel, and further, the biological and physiologically active substance of the present invention in an amount necessary for the treatment of a lesioned part should be mounted. There is an advantage that can be.

  In addition, the stent of the present invention has a layer made of the biological and physiologically active substance of the present invention on the surface of the stent body of the present invention, and further has a layer made of the biodegradable composition of the present invention on its upper surface. It is preferable to have. This is because the biological physiologically active substance of the present invention can be stabilized and the biological physiologically active substance of the present invention can be gradually released into the living body.

Such a layer made of the biological and physiologically active substance of the present invention and a layer made of the biodegradable composition of the present invention are formed on the surface of the stent body of the present invention by the method described later.
Here, the thickness (average thickness) of the layer comprising the biological and physiologically active substance of the present invention is 1 to 100 μm, preferably 1 to 15 μm, more preferably 3 to 7 μm. If the layer has a thickness within this range, it can be easily inserted into a lumen such as a blood vessel, and while considering the physical properties and degradability of the biodegradable composition of the present invention, There is an advantage that the biological and physiologically active substance of the present invention can be loaded in an amount necessary for treatment of the present invention.
The thickness (average thickness) of the layer comprising the biodegradable composition of the present invention is 1 to 75 μm, preferably 1 to 25 μm, more preferably 1 to 10 μm. If the thickness of the layer made of the biodegradable composition of the present invention is too small, there is a possibility that it cannot function as a coating film that completely covers the layer made of the biological and physiologically active substance of the present invention. On the other hand, if the size is too large, the outer shape of the stent itself becomes too large, and there is a possibility that the delivery to the lesioned part may be hindered.

  In the stent of the present invention, there are a plurality of layers composed of the biological physiologically active substance of the present invention and a layer composed of the biodegradable composition of the present invention on the surface of the stent body of the present invention. May be.

  Examples of such a stent include a coiled stent, a mesh stent, and a porous tubular stent.

Examples of the shape of the stent of the present invention include those shown in FIG.
In FIG. 1, a stent body 1 is a cylindrical body that is open at both ends and extends in the longitudinal direction between the ends. The side surface of the cylindrical body has a large number of notch portions that communicate with the outer side surface and the inner side surface. To maintain its shape.
In the embodiment shown in FIG. 1, the stent body 1 is composed of a linear member 2 and has a substantially rhombic element 3 having a notch therein as a basic unit. A plurality of substantially rhombic elements 3 form an annular unit 4 by arranging and coupling substantially rhombus shapes continuously in the minor axis direction. The annular unit 4 is connected to an adjacent annular unit via a linear connecting member 5. Thereby, the some annular unit 4 is continuously arrange | positioned in the axial direction in the state couple | bonded. With such a configuration, the stent body (stent) 1 has a cylindrical body that opens at both ends and extends in the longitudinal direction between the ends. The stent body (stent) 1 has a substantially diamond-shaped notch, and has a structure that can be expanded and contracted in the radial direction of the cylindrical body by deformation of the notch.

  A preferred embodiment of the stent of the present invention shown in FIG. 1 has a layer 6 made of a biological physiologically active substance on the surface of the stent body 1 and further has a layer 7 made of a biodegradable composition on the upper surface thereof. FIG. 2 shows a cross section taken along the line AA in FIG. 3, and FIG. 3 shows a cross section taken along the line BB in FIG.

  1 is a preferred embodiment in which the stent of the present invention shown in FIG. 1 has a layer comprising a biological physiologically active substance 9 and a biodegradable composition 8 on the surface of the stent body 1. FIG. 4 shows the cross section, and FIG. 5 shows the BB cross section of FIG.

  When the stent body 1 is composed of the linear member 2, the length in the width direction of the linear member 2 configured to have a large number of notches is preferably 0.01 to 0.5 mm. And more preferably 0.05 to 0.2 mm.

  As other specific examples of the shape of the stent body having such a radially expandable / contractible structure, an elastic wire as disclosed in Japanese Patent Laid-Open Nos. 9-215753 and 7-529 is coiled. The main body of the stent in which the gap between the elastic wires forms a notch in an example in which a plurality of them are bent and connected to form a cylindrical shape; Japanese Patent Publication No. 8-502428 and Japanese Patent Publication No. 7-5000027 A stent main body in which a gap between elastic wires forms a notch in an example in which a plurality of elastic wires are bent in a zigzag shape and formed into a cylindrical shape as disclosed in Japanese Patent Laid-Open No. 2000-501328 In an example in which an elastic wire is bent into a shape of a snake-like flat ribbon and wound into a helix around a mandrill to form a cylindrical shape as disclosed in Japanese Patent Laid-Open No. 11-212288. 1. Main body of stent in which gaps between wires form notches; as disclosed in Japanese Patent Publication No. 10-503676, the shape of the notches differs from the stent body of FIG. The main body of the stent having a mesh-shaped structure, such as disclosed in JP-A-8-507243, in which the plate-like member is bent into a coil shape and formed into a cylindrical shape between adjacent coil portions. The stent main body etc. in which the gap | interval forms a notch part are mentioned.

  Japanese Patent Publication No. 4-68939 discloses an example in which an elastic plate-like member is formed into a spiral shape to form a cylindrical shape, and a stent body in which a gap between adjacent spiral portions forms a notch and an elastic wire are braided. A cylindrical stent body having a plurality of different structures including a stent body in which a gap between elastic wires forms a notch in an example of a cylindrical shape. In addition, the main stent body may be a leaf spring coil shape, a multiple spiral shape, an atypical tubular shape, or the like.

  Further, FIGS. 2 (a) and 2 (b) of Japanese Patent Publication No. 4-68939 describe a stent body in which an elastic plate member is bent into a spiral shape to form a cylindrical shape. A cylindrical stent body that does not have a notch on the side but is configured to be able to expand and contract in the radial direction of the cylindrical body is also a biodegradable composition of the present invention and a non-degradable composition of the present invention. By using a metal material or the like, the stent body of the present invention can be used. All of these above references and patent applications are hereby incorporated by reference.

  The magnitude | size of the stent of this invention can be suitably selected according to an application location. For example, when used for a coronary artery of the heart, the diameter of a circle (hereinafter, also simply referred to as an “outer diameter”) in a cross section perpendicular to the longitudinal direction (radial direction) before expansion is generally 1.0 to 3.0 mm, The length is preferably 5 to 50 mm and the thickness is preferably 0.01 to 0.5 mm.

  The stent main body 1 shown above is only one aspect, and both end portions are open, and are cylindrical bodies extending in the longitudinal direction between the both end portions. It has a large number of notches that communicate with the inner surface, and a wide range of structures that can expand and contract in the radial direction of the cylindrical body by deforming the notches.

<Stent manufacturing method>
1 illustrates a method for manufacturing a stent of the present invention.
First, in the stent body manufactured by the above-described method, the biological and physiologically active substance of the present invention and the biodegradable composition of the present invention are dissolved in a solvent such as acetone, and a spray, a dispenser, etc. Apply by the conventional method used. Then, the solvent is volatilized.
Alternatively, the biological and physiologically active substance of the present invention is dissolved in a solvent such as acetone and applied by a conventional method using a spray, a dispenser or the like, and then the solvent is volatilized. And the biodegradable composition of this invention is similarly melt | dissolved in acetone etc., it apply | coated by the same method, and a solvent is volatilized.

Here, before applying the biological physiologically active substance of the present invention, the biodegradable composition of the present invention, and the mixture thereof to the stent body, the surface of the stent body of the present invention is chemically treated, or It is preferable to perform an operation such as etching to form fine irregularities on the surface using plasma or the like. The reason is that the adhesion between the stent body of the present invention and the biological and physiologically active substance of the present invention, the biodegradable composition of the present invention, and a mixture thereof is improved.
For the same reason, an adhesive or the like may be applied to the surface of the stent body of the present invention, the stent body of the present invention, the biological physiologically active substance of the present invention, the biodegradable composition of the present invention, and You may heat-bond these mixtures.
By such a method, the stent of the present invention can be manufactured.

<How to use the stent>
The method of using the stent of the present invention having such a shape is the same as usual. For example, when the stent of the present invention is placed in a stenosis that has occurred in a coronary artery, the stent of the present invention having a diameter smaller than the diameter of the coronary artery is attached to the distal balloon of the catheter so as to percutaneously reach the stenosis. Thereafter, the stent of the present invention is expanded by the action of an external force based on the expansion of the balloon to secure the inner diameter of the coronary artery.

  Hereinafter, the present invention will be described more specifically with reference to examples. The present invention is not limited to the following examples.

<Example 1>
A solution of tetrahydrofuran (THF) in which simvastatin (SV), an antihyperlipidemic agent, is dissolved on the outer surface of a stent body (outer diameter 2.0 mm, length 15 mm, made of SUS316L) having the same shape as FIG. SV concentration was 1% by mass) using a spray (manufactured by Micro Spray Gun-II NORDSON). Then, it was placed under vacuum to evaporate THF as a solvent, and an SV layer was formed on the outer surface of the stent body. This confirmed that about 300 μg of SV was applied to the outer surface of the stent body. At this time, the thickness of the SV was about 5 μm.

Next, the layer which consists of a biodegradable composition was formed in the outer surface. The biodegradable composition was produced using the following raw materials and kneading apparatus.
Polylactic acid: Polylactic acid obtained by ring-opening polymerization of L-lactic acid lactide and having a glass transition point of 60 ° C., a melting temperature (melting point) of 168 ° C., and a weight average molecular weight of about 180,000, and in the form of white pellets (Hereinafter also referred to as “PLLA”).
-Montmorillonite: Kunipia F manufactured by Kunimine Industry Co., Ltd.
-Kneading apparatus: A twin screw extruder TEXα30 (caliber 32 mm, L / D = 42) manufactured by Nippon Steel Co., Ltd. was used. The cylinder part of this device consists of 12 blocks C1 to C12. Raw material supply ports are installed in C1 part (throat) and C4 part (side), vents are installed in C3 and C8 parts, and screw kneading part (knee) The positioning zone) is arranged so as to be at positions C5 and C10.

  First, the PLLA is melt-extruded at a temperature of 200 ° C., this molten strand is passed through a roller in a cooling water bath and crushed, and this is cut with a pelletizer, so that the size is about 1 mm × 5 mm × 8 mm. Flaky PLLA was obtained. Next, water was added using a sprayer while stirring montmorillonite with a mixer, and water-swollen montmorillonite was prepared so that the moisture content of montmorillonite was about 30% by mass. Furthermore, the PLLA and the water-swelled montmorillonite were stirred and mixed so that the mass ratio of PLLA was 95% by mass and the substantial montmorillonite ratio was 5% by mass, and used as a raw material to be put into an extruder. The die head and vent port of the extruder were opened, the raw material was supplied from the throat supply port, the cylinder set temperature was set to 50 ° C. flat, and the screw rotation speed was set to 200 rpm for extrusion. Here, the water content was determined from the weight loss after drying 100 g of water-swelled montmorillonite in a vacuum oven at 150 ° C. for 6 hours.

Using a biodegradable composition of polylactic acid and montmorillonite produced by such a method, a No. 2 test piece was prepared for use in a tensile test.
This No. 2 test piece was pre-heated at a temperature of 190 ° C. for 4 minutes using a press molding machine (SA-303, manufactured by Toyo Seiki Co., Ltd.), and then pressed and molded at a pressure of 20 MPa and a temperature of 190 ° C. for 3 minutes.
Here, the No. 2 test piece was subjected to state adjustment for 48 hours at 25 ° C. and 50% relative humidity after production. And the tensile test according to JIS-K7113 was done after that.
Specifically, a tensile test was performed at a test speed of 100 mm / min under the conditions of 25 ° C. and a relative humidity of 50%, and the stress-strain curve shown in FIG. 8 was obtained.

  Next, 1% by mass of THF was added to the biodegradable composition to form a starch candy. And it coated on the upper surface of said SV layer using the ultra micro injection machine (brand name: SUPER SHOT MS-002, Nippon Sosei Kogyo Co., Ltd. make). Then, it put under vacuum, THF which is a solvent was volatilized, and the layer (layer which consists of biodegradable composition) which consists of PLLA and montmorillonite was formed on the upper surface of said SV layer. This layer was about 300 μg and the thickness was about 5 μm.

The stent manufactured by such a method was expanded with a balloon catheter until the final outer diameter was 3.0 mm.
As a result, in the stent of Example 1, as shown in FIG. 6, destruction of the SV layer and / or the layer composed of the biodegradable composition accompanying balloon expansion was not observed.

<Comparative Example 1>
Except not using montmorillonite, a stent was manufactured in the same manner as in Example 1 above, and balloon expansion was performed in the same manner. A similar tensile test was also performed. The obtained stress-strain curve is shown in FIG.
As a result, in the stent of Comparative Example 1, as shown in FIG. 7, destruction of the SV layer and the layer composed of the biodegradable composition accompanying balloon expansion was observed.

FIG. 1 is a side view showing an embodiment of the stent of the present invention. 2 is an enlarged cross-sectional view taken along line AA in FIG. FIG. 3 is an enlarged cross-sectional view taken along line BB in FIG. 4 is an enlarged cross-sectional view taken along line AA in FIG. FIG. 5 is an enlarged cross-sectional view taken along line BB in FIG. FIG. 6 is an enlarged photograph of the stent according to Example 1 after balloon expansion. FIG. 7 is an enlarged photograph of the stent according to Comparative Example 1 after balloon expansion. FIG. 8 is a graph showing a stress-strain curve of the polylactic acid-montmorillonite composition prepared in Example 1. FIG. 9 is a graph showing a stress-strain curve of polylactic acid prepared in Comparative Example 1.

Explanation of symbols

1 Stent body 1
2 Linear member 3 Element of substantially rhombus 4 Ring unit 5 Connecting member 6 Layer made of biological physiologically active substance 7 Layer made of biodegradable composition 8 Biodegradable composition 9 Biologically physiologically active substance

Claims (10)

On the surface of the stent body, a biological physiologically active substance,
It consists of a polymer that is solid at room temperature and decomposes in vivo and an additive. The Young's modulus by tensile test is 100 MPa or more, the elongation at yield point is 20% or less, and the elongation at break is 40% or more. A biodegradable composition which is
Having a stent.   The stent according to claim 1, wherein the biodegradable composition has an absolute value of a difference between a yield point stress and a fracture point stress by a tensile test of 30% or less of the yield point stress.   The biodegradable composition is produced by kneading the polymer and the additive at a temperature of 0 ° C or higher and lower than the melting temperature of the polymer. The stent according to 1.   The stent according to any one of claims 1 to 3, wherein the stent body is made of a metal material.   The stent according to any one of claims 1 to 3, wherein the stent body is made of the biodegradable composition.   The stent according to any one of claims 1 to 5, wherein the polymer is polyester.   The stent according to any one of claims 1 to 6, wherein the additive is a biocompatible compound.   The stent according to any one of claims 1 to 7, further comprising a layer made of the biological physiologically active substance on the surface of the stent body, and further having a layer made of the biodegradable composition on the upper surface thereof.   The stent according to any one of claims 1 to 7, further comprising a layer comprising the biological physiologically active substance and the biodegradable composition on a surface of the stent body.   The biological physiologically active substance is an anticancer agent, immunosuppressive agent, antibiotic, antirheumatic agent, antithrombotic agent, HMG-CoA reductase inhibitor, ACE inhibitor, calcium antagonist, antihyperlipidemic agent, integrin Inhibitors, antiallergic agents, antioxidants, GPIIbIIIa antagonists, retinoids, flavonoids, carotenoids, lipid improvers, DNA synthesis inhibitors, tyrosine kinase inhibitors, antiplatelet drugs, anti-inflammatory drugs, biomaterials, interferon and NO The stent according to any one of claims 1 to 9, which is at least one selected from the group consisting of production promoting substances.

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