JP2020163144A - Cylindrical body for implant - Google Patents

Abstract

To provide a cylindrical body for implant that is superior in kink resistance, and is capable of striking a balance between low extensibility and maintenance of a patency rate.SOLUTION: A cylindrical body for implant includes: a cylindrical base material where a longitudinal elongation rate under the conditions of applying a tensile load of 20 N is 5-100%; a first polymeric layer containing a first polymer comprising a polyalkylene glycol block and a polyhydroxy alkanoic acid block, and having a mass ratio of alkylene glycols residue being 25-60 mass%; and a second polymeric layer containing a second polymer comprising the polyalkylene glycol block and/or the polyhydroxy alkanoic acid block, and having a mass ratio of hydroxyalkanoic acid residue being 75-100 mass%. The first polymeric layer coats the cylindrical base material, and the second polymeric layer coats the first polymeric layer.SELECTED DRAWING: Figure 1

Description

The present invention relates to a tubular body for implants.

Biodegradable polymers are widely used in medical applications such as medical coating materials, vascular embolic materials, sutures, and DDS carriers. Since the medical coating material to be buried in the body is indwelled in the body, it is non-toxic and must be finally decomposed and excreted from the body.

In particular, a coating material that comes into contact with blood may lose its original function if it induces thrombus formation, and thus biocompatibility is required.

Block copolymers of polyalkylene glycol and aliphatic polyester have been reported as biodegradable polymers having such excellent degradability and antithrombotic properties (Patent Documents 1 and 2).

Further, a copolymer obtained by mixing a component selected from L-lactic acid, D, L-lactic acid, glycolic acid and ε-caprolactone and a component selected from polyvinyl alcohol and polyethylene glycol is used as a biodegradable synthetic polymer. In addition to being used, an artificial blood vessel in which these biodegradable synthetic polymers are coated on a tubular material made of fibers has also been reported (Patent Document 3).

JP-A-9-309947 International Publication No. 1996/021056 Japanese Unexamined Patent Publication No. 2004-313310

However, since the block copolymer described in Patent Document 1 has a high content of polyalkylene glycol, it swells when it comes into contact with blood, which leads to the elongation of artificial blood vessels. When the artificial blood vessel is elongated, the inner diameter may be reduced and the blood shear rate is increased. Further, in the case of a base material made of fibers, the decrease in fiber density increases the voids through which blood components enter. In either case, platelet adhesion / aggregation is promoted, leading to thrombus formation.

Since the block copolymer described in Patent Document 2 has a low content of polyalkylene glycol, it does not stretch due to swelling, but has a high Young's modulus. Due to this high Young's modulus, the artificial blood vessel coated with the block copolymer has reduced kink resistance, so that it cannot follow the movement of the living body and buckles, leading to occlusion of the artificial blood vessel.

As described above, since the block copolymer of the prior art is caused by high swelling property and high Young's modulus, even if it is applied to an artificial blood vessel, it leads to elongation of the artificial blood vessel and maintains the required high patency rate. It may not be possible.

Further, in the artificial blood vessel described in Patent Document 3, since polyethylene glycol is mixed with the biodegradable polymer to be coated, polyethylene glycol is eluted at the initial stage of transplantation, and the antithrombotic property is not maintained. Further improvements were needed to use it as a viable implant.

Therefore, an object of the present invention is to provide a tubular body for an implant, which has excellent kink resistance and can achieve both low extensibility and maintenance of patency rate.

As a result of intensive studies to solve the above problems, the present inventors have found the following inventions (1) to (9).
(1) It is composed of a tubular base material having an elongation rate in the major axis direction of 5% to 100% under a tensile load of 20 N, a polyalkylene glycol block and a polyhydroxyalkanoic acid block, and is alkylene glycol. It is composed of a first polymer layer containing a first polymer having a residue mass ratio of 25% by mass to 60% by mass, a polyalkylene glycol block and / or a polyhydroxyalkanoic acid block, and a hydroxyalkanoic acid residue. A second polymer layer containing a second polymer having a mass ratio of 75% by mass to 100% by mass is provided, and the first polymer layer covers the tubular base material and the second polymer layer. Is a tubular body for implants, which covers the first polymer layer, and the first polymer and the second polymer each have a Young ratio of 200 MPa or less when formed into a film.
(2) The tubular body according to (1), wherein the polyalkylene glycol block contains an ethylene glycol residue and / or a propylene glycol residue.
(3) The tubular body according to (1), wherein the polyhydroxyalkanoic acid block contains a residue selected from the group consisting of a lactic acid residue, a glycolic acid residue and a caprolactone residue.
(4) The tubular body according to any one of (1) to (3), wherein the polyalkylene glycol block has a weight average molecular weight of 7,000 to 170,000.
(5) The tubular body according to any one of (1) to (4), wherein the tubular base material satisfies the following formula 1.
(L2-L1) / L1 ≧ 0.1 ・ ・ ・ Equation 1
L1: A marked line is drawn on the outer circumference of the tubular base material at a distance of 5 times the maximum outer diameter when measured without applying stress to the tubular base material, and the longitudinal direction of the tubular base material is long. Distance between marked lines when compressed with a stress of 0.01 cN / dtex L2: The distance of the tubular base material is 5 times the maximum outer diameter when measured without applying stress to the tubular base material. Distance between marked lines when a marked line is drawn on the outer circumference and extended in the long axis direction of the tubular base material with a stress of 0.01 cN / dtex (6) The tubular base material satisfies the following equation 2. The tubular body according to any one of (1) to (5).
0.03 ≦ (ab) / a <0.2 ・ ・ ・ Equation 2
a: Outer diameter of the tubular base material when compressed with a stress of 0.01 cN / dtex in the long axis direction b: The tubular base material when stretched with a stress of 0.01 cN / dtex in the long axis direction Outer diameter (7) The tubular body according to any one of (1) to (6), wherein the inner surface roughness of the tubular base material is 100 μm or less.
(8) An artificial blood vessel comprising the tubular body according to any one of (1) to (7).
(9) A stent graft comprising the tubular body according to any one of (1) to (7).

The tubular body for implants of the present invention makes it possible to maintain kink resistance and a high patency rate that could not be achieved in the past, and can be particularly suitably used as a material for medical equipment for cardiovascular implants.

It is explanatory drawing for drawing a mark line on a tubular base material. It is a conceptual diagram of the apparatus for measuring the distance between the mark lines at the time of compression of a tubular base material. It is a conceptual diagram of the apparatus for measuring the distance between the marked lines at the time of extension of a tubular base material. It is explanatory drawing for measuring the inner surface roughness of a tubular base material.

The tubular body for an implant of the present invention has a tubular substrate having a elongation rate in the major axis direction of 5% to 100% under a tensile load of 20 N, a polyalkylene glycol block, and a polyhydroxyalkanoic acid. It consists of a first polymer layer consisting of blocks and containing a first polymer having a mass ratio of alkylene glycol residues of 25% by mass to 60% by mass, and a polyalkylene glycol block and / or a polyhydroxyalkanoic acid block. A second polymer layer containing a second polymer having a hydroxyalkanoic acid residue mass ratio of 75% by mass to 100% by mass is provided, and the first polymer layer comprises the tubular substrate. The second polymer layer is coated, and the first polymer layer and the second polymer are each characterized by having a Young ratio of 200 MPa or less when formed into a film.

If the elongation rate in the long axis direction under the condition of applying a tensile load of 20 N is 5% or more, the tubular base material easily follows the movement of the living body when embedded in the body, and the elongation rate is 100% or less. If so, it will prevent meandering during the operation and will be easier to fit in the target area. From this, the above-mentioned tubular base material preferably has an elongation rate in the major axis direction of 5% to 100% under the condition of applying a tensile load of 20 N, more preferably 5% to 50%. % -40% is more preferable. The elongation rate in the long axis direction under the condition of applying a tensile load of 20 N can be measured by Measurement Example 4 described later.

The above-mentioned tubular base material is used for implants having excellent elasticity, flexibility and kink resistance (easy bending) by setting the relationship between the following marked line distances L1 and L2 within the range of the following formula 1. Cylindrical bodies can be provided.

(L2-L1) / L1 ≧ 0.1 ・ ・ ・ Equation 1
L1: A marked line is drawn on the outer circumference of the tubular base material at a distance of 5 times the maximum outer diameter when measured without applying stress to the tubular base material, and the long axis of the tubular base material. Distance between marked lines when compressed with a stress of 0.01 cN / dtex in the direction L2: A tubular base at a distance five times the maximum outer diameter when measured without applying stress to the tubular substrate. The distance between the marked lines when a marked line is drawn on the outer circumference of the material and extended in the long axis direction of the tubular base material with a stress of 0.01 cN / dtex.

When the tubular base material is bent, stress is applied in the compression direction on the bent inner peripheral side and stress is applied in the extension direction on the outer peripheral side. However, the above-mentioned tubular base material has the following distances between marked lines L1 and L2. By setting the relationship with the above range, the outer circumference can be sufficiently extended with respect to the inner circumference, so that the kink resistance is excellent.

Here, the stretching operation or the compressing operation with a stress of 0.01 cN / dtex usually corresponds to the stress when a person lightly stretches and compresses the tubular base material by hand in the long axis direction, and is in the above range. In some cases, it means that the operability is good even when a person performs a bending operation by hand, and the elasticity and flexibility are excellent.

The values of the distances L1 and L2 between the marked lines of the tubular base material can be measured according to Measurement Example 6 described later. Further, the value of (L2-L1) / L1 is preferably 0.15 or more, and more preferably 0.18 or more, from the viewpoint that elasticity and flexibility can be further improved. Further, the value of (L2-L1) / L1 is preferably 1.0 or less.

Further, the values of the outer diameter a when compressed, the outer diameter b when expanded and (ab) / a of the tubular base material are a: 0.01 cN / dtex in the major axis direction obtained by Measurement Example 7 described later. It can be derived from the outer diameter of the tubular base material when compressed by stress and b: the outer diameter of the tubular base material when stretched with a stress of 0.01 cN / dtex in the long axis direction. By setting the value of (ab) / a within the range of the following formula 2, the difference in inner diameter of the tubular base material becomes small when elongation such as bending and compression occur at the same time, and a flow path without change is secured. Therefore, turbulence of blood flow does not occur and thrombus formation is suppressed.
0.03 ≦ (ab) / a <0.2 ・ ・ ・ Equation 2
a: Outer diameter of the tubular base material when compressed with a stress of 0.01 cN / dtex in the long axis direction b: The tubular base material when stretched with a stress of 0.01 cN / dtex in the long axis direction Outer diameter

The value of (ab) / a is 0.03 from the viewpoint that the difference in inner diameter of the tubular base material becomes small when expansion and compression such as bending occur at the same time, and a flow path without change can be secured. As mentioned above, it is preferably less than 0.2, and more preferably 0.05 or more and less than 0.15.

In the present specification, the inner surface roughness of a tubular base material refers to an arbitrary point on the outer surface of the tubular base material and a straight line and an inner surface from an arbitrary point on the outer surface toward the center of the tubular base material. the distance between the intersection of the set to D, the shortest D D _s in the tubular base _member, when the longest D was D _l, the difference between D _s and D _l. The center of the tubular base material refers to the point where the variation in the shortest distance from the center of the tubular base material to the inner surface is the smallest. Here, the inner surface roughness of the tubular base material is preferably 100 μm or less, more preferably 80 μm or less, and even more preferably 60 μm or less. From the viewpoint of endothelium formation when used as an artificial blood vessel, the lower limit of the inner surface roughness of the tubular base material is preferably 3 μm or more. By setting the inner surface roughness of the tubular base material within the above range, turbulence does not occur in the fluid even when the inner diameter is small, and blood flow is particularly high even when used as a thin artificial blood vessel. It has the advantage that turbulence does not occur and thrombi are unlikely to form. The inner surface roughness of the tubular base material can be measured according to Measurement Example 8 described later.

The water permeability of a tubular base material is a property that water flows out from the outer surface when a certain pressure is applied to the inner surface of the tubular base material, and the index of water permeability in the present specification is inner. When a pressure of 16 kPa is applied to the surface, the amount (mL) of water flowing out from the outer surface is divided by the unit area (cm ² ) and the unit time (min.). The water permeability is measured in accordance with ISO7198, and the unit area (cm ² ) is the amount (mL) of water flowing out of the tubular base material when a pressure of 16 kPa is applied to the inner surface of the tubular base material. And divided by the unit time (min.). The water permeability of the tubular substrate is 5 mL / cm ² / min. If this is the case, cells and tissues are likely to infiltrate after the first polymer layer and the second polymer layer are decomposed, and the water permeability is 500 mL / cm ² / min. If the following, it becomes easier to prevent blood leakage. Therefore, the water permeability under the condition of applying a pressure of 16 kPa to the inner surface is 5 mL / cm ² / min. ~ 500 mL / cm ² / min. Is preferable, and 50 mL / cm ² / min. ~ 350 mL / cm ² / min. Is more preferable, and 100 mL / cm ² / min. ~ 250 mL / cm ² / min. Is even more preferable.

Further, the tubular base material preferably has a structure such as a woven fabric, a knitted fabric, or a non-woven fabric, and more preferably a structure excluding the bellows structure among those structures. In the case of a structure other than the bellows structure, there is no inner surface roughness, turbulence does not occur even when fluid flows while it is thin, and turbulence does not occur in the blood flow, especially when used for a thin artificial blood vessel. It has the advantage that blood clots are unlikely to form. Specifically, it refers to a woven fabric or a non-pleated structure having a structure in which a mandrel having a spiral or annular corrugated groove is inserted into a fiber cylinder and heated to not be corrugated set.

The above-mentioned tubular base material is a hollow base material made of the following materials, and examples of the material of the tubular base material include synthetic polymers and natural polymers.

The synthetic polymers described above include, for example, polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyvinyl acetate, polyvinylpyrrolidone, polyvinyl alcohol, polyurethane, PTFE, ePTFE, acrylic resin, polyamide, polyacetal, polycarbonate, polyester and polysiloxane, or any of these. Examples thereof include mixtures and copolymers. Examples of the natural polymer include polysaccharides, proteins and natural rubber, and examples of the protein include gelatin and collagen.

As the material of the above-mentioned tubular base material, a material having an arbitrary shape can be used, and examples of the shape of the material include a film, a porous sheet, and a fiber.

When the above-mentioned tubular base material is made of fibers, various organic fibers can be used, but polyester is preferable from the viewpoint of water absorption and deterioration resistance. Examples of the polyester include polyethylene terephthalate and polybutylene terephthalate. Further, a copolymerized polyester obtained by copolymerizing polyethylene terephthalate and polybutylene terephthalate with an aliphatic dicarboxylic acid such as isophthalic acid, 5-sodium sulfoisophthalic acid or adipic acid may be used as an acid component.

The biodegradable polymer refers to a polymer having a property of being decomposed in a living body. Terms that can be used interchangeably with biodegradability include bioabsorbability, biocompatibility, and the like.

The first polymer layer refers to a layer containing a first polymer described later, and the second polymer layer refers to a layer containing a second polymer described later. Further, the first polymer layer coats the tubular base material, and the second polymer layer coats the first polymer layer to form a tubular body for implant. Here, the first polymer layer and the second polymer layer may have a structure such as a knitted fabric, a woven fabric, a non-woven fabric, and a film to form a layer, and are preferably made of a film.

The first polymer described above comprises a polyalkylene glycol block and a polyhydroxyalkanoic acid block, and the second polymer comprises a polyalkylene glycol block and / or a polyhydroxyalkanoic acid block.

The polyalkylene glycol is a polymer obtained by polymerizing one or more kinds of alkylene glycols, and examples of the alkylene glycols include ethylene glycol, propylene glycol, oxyethylene glycol dimethyl ether, oxypropylene glycol monobutyl ether, and oxypropylene glycol diacetate. Examples include polymers containing one or more monomers selected from the group.

Polyhydroxyalkanoic acid is a polymer of one or more types of hydroxyalkanoic acid, and examples of hydroxyalkanoic acid include 2-hydroxypropionic acid (lactic acid), 2-hydroxybutanoic acid, and 2-hydroxypentanoic acid. 2-Hydroxyhexanoic acid, 3-hydroxybutanoic acid (3-hydroxybutyric acid), 3-hydroxypentanoic acid (3-hydroxyvaleric acid), 3-hydroxyhexanoic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3 -Hydroxynonanoic acid, 3-hydroxydecanoic acid, 4-hydroxypentanoic acid, 4-hydroxyhexanoic acid, 4-hydroxyheptanoic acid, 4-hydroxyoctanoic acid, 5-hydroxyhexanoic acid, 5-hydroxyheptanoic acid, 6-hydroxy Heptanoic acid, 6-hydroxyoctanoic acid, 8-hydroxynonanonic acid, 8-hydroxydecanoic acid, 9-hydroxydecanoic acid, 9-hydroxyundecanoic acid, 10-hydroxyundecanoic acid, 10-hydroxydodecanoic acid, 11-hydroxydodecanoic acid Alternatively, 12-hydroxytridecanoic acid can be mentioned.

The mass ratio of the alkylene glycol residue refers to the mass ratio of the alkylene glycol residue to the mass of the polymer contained in the first polymer and / or the second polymer, and the mass ratio of the hydroxyalkanoic acid residue is. , Refers to the mass ratio of hydroxyalkanoic acid residues to the mass of the polymer contained in each of the first polymer and the second polymer. Here, the masses of these residues are calculated from the numerical values obtained by ¹ H-NMR measurement, as described in Measurement Example 1 described later.

In the first polymer, when the mass ratio of the alkylene glycol residue is 25% by mass or more, suitable antithrombotic property is obtained, and when 60% by mass or less, suitable flexibility, that is, low Young's modulus is obtained. Therefore, in order to achieve both suitable antithrombotic properties and low Young's modulus, the first polymer having a mass ratio of alkylene glycol residues of 25% by mass to 60% by mass is preferable, and 27% by mass to 50% by mass. More preferably, it is more preferably 30% by mass to 40% by mass.

In the second polymer, when the mass ratio of the hydroxyalkanoic acid residue is 75% by mass or more, suitable flexibility, that is, low Young's modulus is obtained. A second polymer having a hydroxyalkanoic acid residue mass ratio of 75% by mass to 100% by mass is preferable, and 80% by mass to 95% by mass, in order to obtain a tubular body having low elongation due to further lower swelling property. It is more preferable that it is 85% by mass to 90% by mass.

The mass ratio of caprolactone residue refers to the mass ratio of caprolactone residue to the mass of the polymer contained in the first polymer and / or the second polymer, and as mentioned in Measurement Example 1 described later, ¹ It is calculated from the numerical value obtained by H-NMR measurement. When the mass ratio of the caprolactone residue is 15% by mass or more, the Young's modulus becomes a suitable value, and when it is 80% or less, it has a suitable degradability. Therefore, in order to achieve both a suitable Young ratio and degradability, a first polymer and / or a second polymer having a caprolactone residue mass ratio of 15% by mass to 80% by mass is preferable, and 20% by mass is preferable. It is more preferably ~ 70% by mass, and even more preferably 25% by mass to 60% by mass.

The mass ratio of glycolic acid residue refers to the mass ratio of glycolic acid residue to the mass of the polymer contained in the first polymer and / or the second polymer, as described in Measurement Example 1 described later. , ¹ Calculated from the numerical values obtained by H-NMR measurement. In order to obtain a suitable Young's modulus, the first polymer and / or the second polymer having a glycolic acid residue mass ratio of 10% by mass or less is preferable, and 7% by mass or less is more preferable. It is more preferably mass% or less.

The polyalkylene glycol block may be a single polyalkylene glycol molecule, a copolymer of a plurality of polyalkylene glycol molecules, or may be linked via a linker. For example, in the case of a single piece, polyethylene glycol or polypropylene glycol is preferable, and in the case of a copolymer or a linking polymer, a copolymer or a linking polymer composed of polyethylene glycol and polypropylene glycol is preferable. These polyalkylene glycol blocks contain ethylene glycol residues and / or propylene glycol residues. The weight average molecular weight of the polyalkylene glycol molecules constituting the polyalkylene glycol block is preferably 7,000 to 170,000, more preferably 8,000 to 100,000, still more preferably 10,000 to 50,000.

The polyhydroxyalkanoic acid block may be a single polyhydroxyalkanoic acid molecule, a copolymer of a plurality of polyhydroxyalkanoic acid molecules, or may be linked via a linker. For example, in the case of a single substance, polylactic acid, polycaprolactone or polyglycolic acid is preferable, and in the case of a copolymer or linked polymer, a copolymer or linked polymer composed of polylactic acid, polycaprolactone and polyglycolic acid is preferable. These polyhydroxyalkanoic acid blocks contain residues selected from the group consisting of lactic acid residues, glycolic acid residues and caprolactone residues. The weight average molecular weight of the polyhydroxyalkanoic acid molecules constituting the polyhydroxyalkanoic acid block is preferably 1,000 to 100,000, more preferably 10,000 to 80,000, still more preferably 20,000 to 50,000. ..

The Young's modulus of the film 1 made of the first polymer, the Young's modulus of the film 2 made of the second polymer, and the Young's modulus of the blended film obtained by blending the first polymer and the second polymer are It can be evaluated by the method described in Measurement Example 2 described later. In order for the tubular body for implants coated with the first polymer layer and the second polymer layer to exhibit good kink resistance, the Young's modulus of the film 1, the film 2, and the blend film is 200 MPa, respectively. It is preferably less than or equal to, more preferably 100 MPa or less, and even more preferably 10 MPa or less.

When the first polymer layer or the second polymer layer is a film, the weight average molecular weights of the first polymer and the second polymer are preferably 10,000 or more, respectively. The upper limit is not particularly limited, but in order to improve moldability, it is preferably 1,600,000 or less, more preferably 800,000 or less, and even more preferably 400,000 or less. The weight average molecular weight can be determined by gel permeation chromatography (GPC) method, for example, by the following method.

In this method, the first polymer and the second polymer are dissolved in chloroform and passed through a 0.45 μm syringe filter (DISMIC-13HP; manufactured by ADVANTEC) to remove impurities and the like, and then measured by GPC. The weight average molecular weights of the first polymer and the second polymer are calculated.
Device name: Prominence (manufactured by Shimadzu Corporation)
Mobile phase: Chloroform (for HPLC) (manufactured by Wako Pure Chemical Industries, Ltd.)
Flow velocity: 1 mL / min
Column: TSKgel GMHHR-M (φ7.8 mm x 300 mm; manufactured by Tosoh Corporation)
Detector: UV (254 nm), RI
Column, detector temperature: 35 ° C
Standard substance: polystyrene

The above-mentioned swelling property refers to the property that the polymer contains water and swells when immersed in water, and in the present specification, the index of water swelling property is the water swelling rate.

The water swelling rate of the film 1, the film 2, and the blended film can be evaluated by the method described in Measurement Example 3 described later. If the water swelling rate is -10% or more, the film 1, film 2, and the blended film are prevented from peeling from the tubular substrate even when the film shrinks, and if it is 20% or less, the film 1, film 2, and the blend are blended. Even when the film swells, it is possible to prevent the formation of thrombosis due to the tubular body for implant being stretched too much. Therefore, the water swelling rate of the film 1, the film 2, and the blended film is preferably −10% to 20%, more preferably −5% to 15%, and even more preferably 0% to 15%.

The first polymer and the second polymer are, for example, a method of ring-opening polymerization of a cyclic monomer in the presence of an initiator and a catalyst (ring-opening polymerization method), or a block copolymer in the presence of a catalyst or a condensing agent. It can be synthesized by a method in which similar or different block copolymers are bonded to both ends one molecule at a time via the ends (multiplication method) and a method in which a ring-opening polymerization method and a mulching method are combined.

Examples of cyclic monomers include D, L-lactide, L-lactide, glycolide, D, L-lactide-co-glycolide, L-lactide-co-glycolide, ε-caprolactone, γ-butyrolactone, δ-valerolactone, Examples thereof include ε-caprolactone-co-lactic acid and ε-caprolactone-co-glycolic acid-co-lactic acid.

As the catalyst for production by the ring-opening polymerization method, ordinary polymerization catalysts such as germanium-based, titanium-based, antimony-based and tin-based catalysts can be used. Specific examples of such a polymerization catalyst include tin (II) octylate, antimony trifluoride, zinc powder, dibutyltin oxide (IV) and tin oxalate (II). The method of adding the catalyst to the reaction system is not particularly limited, but it is preferably a method of adding the catalyst in a state of being dispersed in the raw material at the time of charging the raw material or in a state of being dispersed in the raw material at the start of depressurization. The amount of the catalyst used is 0.01% by mass to 3% by mass, more preferably 0.05% by mass to 1.5% by mass, in terms of metal atoms, based on the total amount of the monomers used.

Metal catalysts for production by the mulching method include metals such as tin, titanium, lead, zinc, cobalt, iron, lithium or rare earth, and their metal alkoxides, metal halogen compounds, organic carboxylates, carbonates and sulfates. Alternatively, an oxide may be mentioned, but a tin compound is preferable from the viewpoint of polymerization reactivity.

Examples of the tin compound include tin powder, tin (II) chloride, tin (IV) chloride, tin (II) bromide, tin (IV) bromide, ethoxytin (II), t-butoxystin (IV), and isopropoxy. Tin (IV), tin acetate (II), tin acetate (IV), tin octylate (II), tin laurate (II), tin myristate (II), tin palmitate (II), tin stearate (II) ), Tin oleate (II), tin linoleate (II), acetylacetone tin (II), tin oxalate (II), tin lactate (II), tin tartrate (II), tin pyrophosphate (II), p- Tin phenol sulfonate (II), bis (methane sulfonic acid) tin (II), tin sulfate (II), tin oxide (II), tin oxide (IV), tin sulfide (II), tin sulfide (IV), oxidation Dimethyltin (IV), Methylphenyltin Oxide (IV), Dibutyltin Oxide (IV), Dioctyltin Oxide (IV), Diphenyltin Oxide (IV), Tributyltin Oxide, Triethyltin Hydroxide (IV), Triphenyltin Hydroxide (IV) ), Tributyltin hydride, monobutyltin (IV) oxide, tetramethyltin (IV), tetraethyltin (IV), tetrabutyltin (IV), dibutyldiphenyltin (IV), tetraphenyltin (IV), tributyltin acetate (IV). , Triisobutyltin acetate (IV), triphenyltin acetate (IV), dibutyltin diacetate, dibutyltin dioctanoate, dibutyltin dilaurate (IV), dibutyltin maleate (IV), dibutyltin bis (acetylacetonate), tributyltin chloride ( IV), dibutyltin dichloride, monobutyltin trichloride, dioctyltin dichloride, triphenyltin chloride (IV), tributyltin sulfide, tributyltin sulfate, tin methanesulfonate (II), tin ethanesulfonate (II), trifluoromethanesulfone Tin (II) oxide, ammonium hexachlorotin (IV) acid, dibutyltin sulfide, diphenyltin sulfide, triethyltin sulfate, phthalocyanine tin (II) and the like can be used.

Examples of non-metal catalysts and condensing agents used in the mulching method include 4,4-dimethylaminopyridine, 4,4-dimethylaminopyridinium p-toluenesulfonate, and 1- [3- (dimethylamino) propyl]. -3-ethylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, N, N'-dicyclohexylcarbodiimide, N, N'-diisopropylcarbodiimide, N, N'-carbonyldiimidazole, 1,1 '-Carbonyldi (1,2,4-triazole), 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium = chloride n hydrate, trifluo Lomethanesulfonic acid (4,6-dimethoxy-1,3,5-triazine-2-yl)-(2-octoxy-2-oxoethyl) dimethylammonium, 1H-benzotriazole-1-yloxytris (dimethylamino) phosphonium Hexafluorophosphate, 1H-benzotriazole-1-yloxytripyrrolidinophosphonium hexafluorophosphate, (7-azabenzotriazole-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate, chlorotri Pyrrolidinophosphonium hexafluorophosphate, bromotris (dimethylamino) phosphonium hexafluorophosphate, 3- (diethoxyphosphoryloxy) -1,2,3-benzotriazine-4 (3H) -one, O- (Benzotriazole-1-yl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (7-azabenzotriazole-1-yl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (N-succinimidyl) -N, N, N', N'-tetramethyluronium tetrafluoroborate, O- (N-succinimidyl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (3,4-dihydro-4-oxo-1,2,3-benzotriazine-3-yl) -N, N, N ', N'-Tetramethyluronium tetrafluoroborate, S- (1-oxide-2-pyridyl) -N, N, N', N'-Tetramethylthiouronium tetrafluoroborate, O- [2 -Oxo-1 (2H) -pyridyl] -N, N, N', N'-tetramethyluronium tetrafluoroborate, {{[(1-cyano-2-ethoxy-2-oxoe) Tylidene) Amino] Oxy} -4-morpholinomethylene} Dimethylammonium hexafluorophosphate, 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate, 1- (chloro-1-pyrrolidinyl methylene) Pyrrolidinium hexafluorophosphate, 2-fluoro-1,3-dimethylimidazolinium hexafluorophosphate and fluoro-N, N, N', N'-tetramethylformamidinium hexafluorophosphate, etc. Can be used.

When mulching, a linker molecule having two or more carboxyl groups, isocyanate groups, amino groups or hydroxyl groups may be used for mulching.

Examples of the linker molecule having two or more carboxyl groups include a dicarboxylic acid, citric acid, and a multi-branched polymer having two or more carboxyl groups at the branched ends, or an acid halide of the dicarboxylic acid, citric acid, and the multi-branched polymer. , Acid anhydrides or esters. That is, the carboxylic acid group may be converted into an acid halide structure, an ester structure or an acid anhydride structure. Examples of the dicarboxylic acid include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, malic acid, tartaric acid and dodecanedioic acid. Examples of the multi-branched polymer include hyper-branched polymers and dendrimers.

Examples of the linker molecule having two or more isocyanate groups include hexamethylene diisocyanate (HDI), 4,4′-diphenylmethane diisocyanate (MDI), 4,4′-dicyclohexylmethane diisocyanate, cyclohexyldiisocyanate (CHDI) and 2,4. -Toluene diisocyanate (TDI) and the like can be mentioned.
Examples of the linker molecule having two or more amino groups include ethylenediamine, putrescine, cadaverine, hexamethylenediamine and phenylenediamine.

Examples of the linker molecule having two or more hydroxyl groups include ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, and 1,7-heptanediol. 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1,13-tridecanediol, 1,14-tetradecanediol, Examples thereof include 1,15-pentadecanediol, 1,16-hexadecanediol and oxaaliphatic diol.

When a linker molecule having a plurality of carboxyl groups, isocyanate groups, amino groups and hydroxyl groups in the same molecule is used as the linker molecule, a branched copolymer in which the linker is a branch point can be synthesized. Examples of the linker having a plurality of carboxyl groups, isocyanate groups, amino groups and hydroxyl groups in the same molecule include 2,2-bis (hydroxymethyl) propionic acid, malic acid, diaminediol and the like.

By reacting polyalkylene glycol (both terminal hydroxyl groups) with the above linker molecule in advance or converting the hydroxyl group into a functional group, polyalkylene glycol having a carboxyl group, an isocyanate group, or an amino group at both ends or one end can be obtained. Polyalkylene glycols having a carboxyl group, an isocyanate group, or an amino group can be obtained, and a copolymer can be produced using these as raw materials.

When the polymerization reaction has a living property, that is, when the polymerization reaction can be started continuously from the end of the polymer, the operation of adding the monomer to the block copolymer solution after the polymerization reaction is completed is repeated. And it can be multi-layered.

In the present specification, the term "residue" means, in principle, a repetition of a chemical structure derived from the monomer in the chemical structure of a block copolymer obtained by polymerizing two or more kinds of monomers containing the monomer. Say the unit.

For example, when lactic acid (CH ₃ CH (OH) COOH) and caprolactone (ε-caprolactone) represented by the following chemical formula (I) are polymerized to form a block copolymer of lactic acid and caprolactone, the lactic acid residue is , The caprolactone residue has the structure represented by the following chemical formula (II), and the caprolactone residue has the structure represented by the following chemical formula (III).

As an exception, when a dimer such as lactide is used as the monomer, the "residue" means one of the two-fold repeating structures derived from the dimer. For example, when dilactide ( _L -(-)-lactide) represented by the following chemical formula (IV) and caprolactone are polymerized, the chemical structure of the block copolymer is represented by the above chemical formula (II) as a dilactide residue. A structure is formed in which the above-mentioned structure is repeated twice. In this case, one of them is regarded as a lactic acid residue, and it is considered that two lactic acid residues are formed due to dilactide.

The properties of the first polymer and the second polymer can be analyzed as follows. For example, the solid obtained by immersing the isolated first polymer or the second polymer in a solvent such as chloroform and drying the extract can be measured as described in Measurement Examples 1 to 3 described later. Do.

A kink radius can be mentioned as an index for evaluating kink resistance. The kink radius refers to the minimum loop radius that does not buckle when a loop is formed from a tubular body for implant and the diameter of the loop is gradually reduced. The kink radius can be evaluated by the method given in Measurement Example 10 described later. After transplantation into a living body, the kink radius is preferably 15 mm or less in order to easily follow the movement of surrounding tissues and obtain a high patency rate, and to facilitate transplantation to a bent portion. It is more preferably 10 mm or less.

The average layer thickness of the first polymer layer and the second polymer layer refers to an average value calculated from the total thickness of the first polymer layer and the second polymer layer in the cross section of the tubular body for implant, and is a measurement example described later. It can be evaluated by the method listed in 11. When the average layer thickness of the first polymer layer and the second polymer layer is 1 μm or more, the pressure resistance is improved, and when the layer thickness is 500 μm or less, the time required for decomposition is a suitable time. Therefore, the average layer thickness of the first polymer layer and the second polymer layer is preferably 1 μm to 500 μm, more preferably 10 μm to 300 μm, and even more preferably 20 μm to 200 μm.

As described above, if the water swelling rate when the first polymer layer and the second polymer layer are overlapped is −10% to 20%, thrombus formation due to peeling or swelling can be prevented. At this time, the thickness of each of the first polymer layer and the second polymer layer is not particularly limited, but if the water swelling rate of the first polymer layer is high, the layer thickness of the second polymer layer may be increased. Good.

The inner diameter of the tubular base material is preferably 1 mm to 10 mm, more preferably 2 mm to 4 mm in consideration of use as an artificial blood vessel or a stent graft.

Artificial blood vessels are medical devices used to replace pathological living blood vessels such as arteriosclerosis, or to form bypasses and shunts. Examples of the material of the artificial blood vessel include cloth, polytetrafluoroethylene, biomaterial, synthetic polymer material and the like, but cloth is preferable because it is easy to impart anticoagulant ability.

The patency rate is an index for evaluating artificial blood vessels. In human clinical practice, it has been reported that in bypass surgery for arteriosclerosis obliterans of the lower extremities, the patency rate is 60% when an artificial blood vessel is used as a substitute blood vessel, whereas it is 80% when an autologous vein is used. There is. For cardiovascular implants such as coronary artery bypass grafting of the heart, autologous veins are selected instead of artificial blood vessels in consideration of postoperative occlusion and stenosis, so the difference in patency rate is about 20% for cardiovascular implants. Has great clinical significance. However, the autologous vein also has a problem that there is a problem that there is a patient who needs excision surgery and the burden on the patient is heavy, or the quality is poor and cannot be used in the first place. Therefore, an artificial blood vessel having a patency rate equal to or higher than that of an autologous vein, that is, an artificial blood vessel having a patency rate of 80% or more is of great clinical significance.

The anticoagulant ability refers to a property of preventing blood coagulation and suppressing thrombus formation, and as a method of imparting anticoagulant ability, a method of imparting heparin or a heparin derivative to the surface of a material can be mentioned.

A stent graft is a medical device that combines a stent and an artificial blood vessel (graft), and is used for indwelling in a living blood vessel to treat an aneurysm.

Hereinafter, the present invention will be described in detail with reference to Reference Examples, Examples and Comparative Examples, but the present invention is not limited thereto.

(Reference example 1)
50.0 g of L-lactide (PURASORB® L; manufactured by PURAC) and 38.5 mL of ε-caprolactone (manufactured by Wako Pure Chemical Industries, Ltd.) were collected in a separable flask as monomers. 0.29 g of tin octylate (II) (manufactured by Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 14.5 mL of toluene (ultra-dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. 90 μL of ion-exchanged water was added as an initiator, a cocatalytic reaction was carried out at 90 ° C. for 1 hour, and then a copolymerization reaction was carried out at 150 ° C. for 6 hours to obtain crude polyhydroxyalkanoic acid A.

The obtained crude polyhydroxyalkanoic acid A was dissolved in 100 mL of chloroform and added dropwise to 1400 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated 3 times, and the precipitate was dried under reduced pressure at 70 ° C. to obtain polyhydroxyalkanoic acid A.

0.56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (Messmore, Benjamin W. et al., Journal of the American Chemical Society, 2004, 2004) based on 15.0 g of the obtained polyhydroxyalkanoic acid A. (Synthesized by the method described in 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 1 purified as a precipitate.

(Reference example 2)
14.2 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1, 0.41 g of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich), at both ends. 0.42 g of polyethylene glycol having a carboxyl group (weight average molecular weight 10,200) was mixed, and 0.56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (Messmore, Benjamin W. et al., Journalal) was mixed as a catalyst. Of the American Chemical Society, 2004, 126, 14452. Synthesized by the method described) and 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 2 purified as a precipitate.

(Reference example 3)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 13.4 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 0. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 0.83 g, respectively. Specifically, 13.4 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were added. 82 g and 0.83 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 3 purified as a precipitate.

(Reference example 4)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 11.7 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 1. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 1.67 g, respectively. Specifically, 11.7 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 63 g and 1.67 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of 4,4-dimethylaminopyridinium p-toluenesulfonic acid (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 4 purified as a precipitate.

(Reference example 5)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 10.9 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 2. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 2.08 g in 04 g. Specifically, 10.9 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 04 g, 2.08 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was mixed, and 0.56 g of 4,4-dimethylaminopyridinium p-toluenesulfonic acid (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 5 purified as a precipitate.

(Reference example 6)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 10.1 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 2. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 2.50 g to 45 g. Specifically, 10.1 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 45 g and 2.50 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of 4,4-dimethylaminopyridinium p-toluenesulfonic acid (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 6 purified as a precipitate.

(Reference example 7)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 8.40 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 3. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 3.33 g to 27 g. Specifically, 8.40 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 27 g and 3.33 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of 4,4-dimethylaminopyridinium p-toluenesulfonic acid (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 7 purified as a precipitate.

(Reference example 8)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 6.75 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 3. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 3.33 g to 27 g. Specifically, 6.75 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 27 g and 3.33 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of 4,4-dimethylaminopyridinium p-toluenesulfonic acid (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 8 purified as a precipitate.

(Reference example 9)
The amount of polyhydroxyalkanoic acid A added was 14.2 g to 3.50 g, and the amount of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) was 0.41 g to 5. It was prepared in the same manner as in Reference Example 2 except that the amount of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) was changed from 0.42 g to 5.80 g to 70 g. Specifically, 3.50 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 70 g and 5.80 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) were mixed, and 0.56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 9 purified as a precipitate.

(Reference example 10)
70.7 g of L-lactide (PURASORB (registered trademark) L; manufactured by PURAC) and 19.0 g of glycolide (manufactured by PURAC) were collected in a separable flask as monomers. 0.29 g of tin octylate (II) (manufactured by Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 14.5 mL of toluene (ultra-dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. , 388 μL of ion-exchanged water was added as an initiator, a cocatalytic reaction was carried out at 90 ° C. for 1 hour, and then a copolymerization reaction was carried out at 130 ° C. for 6 hours to obtain crude polyhydroxyalkanoic acid B.

The obtained crude polyhydroxyalkanoic acid B was dissolved in 100 mL of chloroform and added dropwise to 1400 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated 3 times, and the precipitate was dried under reduced pressure at 70 ° C. to obtain polyhydroxyalkanoic acid B.

9.81 g of the obtained polyhydroxyalkanoic acid B and 5.22 g of the polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 were mixed, and 0.56 g of p-toluenesulfonic acid 4,4- was used as a catalyst. Dimethylaminopyridinium (synthesized by the method described in Meshmore, Benjamin W. et al., Journal of the Amino Chemical Society, 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (Wako Pure Chemical Substances). (Manufactured by Kogyo Co., Ltd.) was added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 10 purified as a precipitate.

(Reference example 11)
It was prepared in the same manner as in Reference Example 10 except that the addition amount of polyhydroxyalkanoic acid B was changed from 9.81 g to 0.33 g and the addition amount of polyhydroxyalkanoic acid A was changed from 5.22 g to 14.7 g. .. Specifically, 0.33 g of polyhydroxyalkanoic acid B obtained in the same manner as in Reference Example 10 and 14.7 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 were mixed and 0 as a catalyst. .56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (synthesized by the method described in Meshmore, Benjamin W. et al., Journal of the American Chemical Society, 2004, 126, 14452.) And 0.20 g. 4,4-Dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 11 purified as a precipitate.

(Reference example 12)
2. Addition of polyhydroxyalkanoic acid A from 14.2 g to 10.1 g, and addition of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) from 0.41 g to 4. Instead of adding 0.42 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200) to 40 g, 0.50 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 1,200). It was created in the same manner as in Reference Example 2 except that it was changed to. Specifically, 10.1 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich) were used. 40 g and 0.50 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 1,200) were mixed, and 0.56 g of p-toluenesulfonic acid 4,4-dimethylaminopyridinium (Messmore, Benjamin W.) was used as a catalyst. et al., Journal of the American Chemical Society, synthesized by the method described in 2004, 126, 14452.) And 0.20 g of 4,4-dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) were added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 12 purified as a precipitate.

(Reference example 13)
Instead of adding 0.41 g of polyethylene glycol having hydroxy groups at both ends (weight average molecular weight 10,000; manufactured by Sigma Aldrich), a copolymer of polyethylene glycol having hydroxy groups at both ends and polypropylene glycol (number average). Molecular weight 8,400, 80% by mass of polyethylene glycol; manufactured by Sigma Aldrich Co., Ltd. Instead of adding 0.42 g of polyethylene glycol having carboxyl groups at both ends (weight average molecular weight 10,200), both ends It was prepared in the same manner as in Reference Example 2 except that the copolymer of polyethylene glycol and polypropylene glycol having a carboxyl group (number average molecular weight 8,600) was changed to 0.35 g. Specifically, 14.2 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and a copolymer of polyethylene glycol and polypropylene glycol having hydroxy groups at both ends (number average molecular weight 8,400, polyethylene). 0.34 g of glycol (manufactured by Sigma Aldrich) and 0.35 g of a copolymer of polyethylene glycol and polypropylene glycol having carboxyl groups at both ends (number average molecular weight 8,600) were mixed to obtain 0. 56 g of 4,4-dimethylaminopyridinium p-toluenesulfonate (synthesized by the method described in Messmore, Benjamin W. et al., Journal of the Polymer Chemical Society, 2004, 126, 14452.) And 0.20 g. 4,4-Dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 13 purified as a precipitate.

(Reference example 14)
The amount of polyhydroxyalkanoic acid A added was increased from 14.2 g to 10.9 g, and a copolymer of polyethylene glycol and polypropylene glycol having hydroxy groups at both ends (number average molecular weight 8,400, polyethylene glycol 80% by mass; sigma aldrich). The addition amount of (manufactured by the company) was 0.34 g to 1.71 g, and the addition amount of a copolymer of polyethylene glycol and polypropylene glycol having carboxyl groups at both ends (number average molecular weight 8,600) was 0.35 g to 1. It was prepared in the same manner as in Reference Example 13 except that it was changed to 75 g. Specifically, 10.9 g of polyhydroxyalkanoic acid A obtained in the same manner as in Reference Example 1 and a copolymer of polyethylene glycol and polypropylene glycol having hydroxy groups at both ends (number average molecular weight 8,400, polyethylene). 1.71 g of glycol (manufactured by Sigma Aldrich) and 1.75 g of a copolymer of polyethylene glycol and polypropylene glycol having carboxyl groups at both ends (number average molecular weight 8,600) were mixed to generate 0. 56 g of 4,4-dimethylaminopyridinium p-toluenesulfonate (synthesized by the method described in Messmore, Benjamin W. et al., Journal of the Polymer Chemical Society, 2004, 126, 14452.) And 0.20 g. 4,4-Dimethylaminopyridine (manufactured by Wako Pure Chemical Industries, Ltd.) was added. Under an argon atmosphere, these were dissolved in 28 mL of dichloromethane (dehydrated) (manufactured by Wako Pure Chemical Industries, Ltd.), and 2.06 g of dicyclohexylcarbodiimide (manufactured by Sigma Aldrich), which is a condensing agent dissolved in 7 mL of dichloromethane, was added. Then, it was condensed and polymerized at room temperature for 2 days.

60 mL of chloroform was added to the reaction mixture, and the mixture was added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dissolved in 100 mL of chloroform and added dropwise to 1000 mL of methanol in a stirred state to obtain a precipitate. This operation was repeated twice to obtain a block copolymer of Reference Example 14 purified as a precipitate.

Since the amount of each raw material added was changed, the molar ratios of lactic acid residue, glycolic acid residue, caprolactone residue, ethylene glycol residue and propylene glycol residue in the block copolymers of Reference Examples 1 to 14 above. Has been changed. Therefore, for Reference Examples 1 to 14 above, the molar ratio of each residue is measured by hydrogen nuclear magnetic resonance ( ¹ H-NMR), and from this, the lactic acid residue, caprolactone residue and glycolic acid in each block copolymer are measured. The mass ratios of residues, ethylene glycol residues, propylene glycol residues, and hydroxyalkanoic acid residues were calculated. The values of Reference Examples 1 to 14 are shown in Table 1.

(Measurement example 1: Measurement of mass ratio of each residue by hydrogen nuclear magnetic resonance ( ¹ H-NMR))
The block copolymers of Reference Examples 1 to 14 were dissolved in deuterated chloroform and measured by ¹ H-NMR at room temperature using JNM-EX270 (manufactured by JEOL Ltd.). Based on each peak of ¹ H-NMR obtained, the molar ratio of lactic acid residue, glycol residue, caprolactone residue, ethylene glycol residue and propylene glycol residue in the block copolymers of Reference Examples 1 to 14 Were calculated respectively. Specifically, in the case of a lactic acid residue, the hydrogen atom at the α-position (chemical shift value: about 5.2 ppm), which is a methylene group, is a characteristic peak, so this is based on the integrated value with all signals. In the case of a caprolactone residue, the hydrogen atom at the α-position (chemical shift value is about 2.3 ppm), which is a methylene group, is a characteristic peak, so this is integrated with the total signal. The molar ratio is calculated based on the value, and in the case of glycolic acid residues, the hydrogen atom at the α-position, which is a methylene group (chemical shift value is about 4.8 ppm), is a characteristic peak, so this is all. The molar ratio is calculated based on the integrated value with the signal, and in the case of an ethylene glycol residue, the four hydrogen atoms of the ethylene group (chemical shift value: about 3.6 ppm) are characteristic peaks. The molar ratio was calculated based on the integrated value with all signals.

From the molar ratios obtained as a result of the above, ethylene glycol residues, lactic acid residues, caprolactone residues, glycolic acid residues and propylene glycol residues in the block copolymers of Reference Examples 1 to 9 were used using the following formulas 3 to 8. The mass ratio of groups was calculated. Moreover, the sum of the lactic acid residue, the glycol residue and the caprolactone residue was calculated as the mass ratio of the hydroxyalkanoic acid residue. The results are shown in Table 1.
W _PEG (%) = (M _EG × x _EG ) / Mx _total × 100 ・ ・ ・ Equation 3
W _PLA (%) = (M _LA x x _LA ) / M x _total x 100 ... Equation 4
W _PCL (%) = (M _CL × x _CL ) / Mx _total × 100 ・ ・ ・ Equation 5
W _PGA (%) = (M _GA x x _GA ) / M x _total x 100 ... Equation 6
W _PPG (%) = (M _PG × x _PG ) / Mx _total × 100 ・ ・ ・ Equation 7
Mx _total = M _EG x x _EG + M _LA x x _LA + M _CL x x _CL + M _GA x x _GA + M _PG x x _PG ... Equation 8

W _PEG : Mass ratio of ethylene glycol residues M _EG : Molecular weight of ethylene glycol residues x _EG : Molar ratio of ethylene glycol residues

W _PLA : Mass ratio of lactic acid residue M _LA : Molecular weight of lactic acid residue x _LA : Molar ratio of lactic acid residue

W _PCL : Mass ratio of caprolactone residues M _CL : Molecular weight of caprolactone residues x _CL : Molar ratio of caprolactone residues

W _PGA : Mass ratio of glycolic acid residue M _GA : Molecular weight of glycolic acid residue x _GA : Molar ratio of glycolic acid residue

W _PPG : Mass ratio of propylene glycol residue M _PG : Molecular weight of propylene glycol residue x _PG : Molar ratio of propylene glycol residue

The refined products of the block copolymers of Reference Examples 1 to 14 were dried under reduced pressure (100 Pa) at room temperature for one day and night. Then, the block copolymer was dissolved in chloroform so as to have a concentration of 5% by mass, the solution was transferred onto a Teflon (registered trademark) chalet, and dried at normal pressure and room temperature for 24 days. This was dried under reduced pressure (100 Pa) and at room temperature for one day and night to obtain films made of the block copolymers of Reference Examples 1 to 14, respectively.

(Measurement example 2: Tension test)
Young's modulus is measured for the obtained film made of the block copolymers of Reference Examples 1 to 14 in order to observe the characteristics of the film state. Specifically, a film made of the block copolymers of Reference Examples 1 to 12 was cut into strips (50 mm × 5 mm × 0.1 mm), and the film was used for the Tensiron universal testing machine RTM-100 (manufactured by Orientec Co., Ltd.). A film made of block copolymers of Reference Examples 1 to 12 is attached so that the distance between chucks in the length direction is 10 mm, a tensile test is performed under the following condition A, and measurement is performed according to JIS K6251 (2010). By reading the slope of the stress / strain curve corresponding between the two strain points of 0.2% and ε2 = 0.3%, the Young's modulus (MPa) of the film made of the block copolymers of Reference Examples 1 to 14 can be determined. Obtained. However, Young's modulus may be calculated as the slope between two points or by the method of least squares. The results are shown in Table 1.
(Condition A)
Equipment name: Tensilon universal tensile tester RTM-100 (manufactured by Orientec Co., Ltd.)
Initial length: 10 mm
Tensile speed: 500 mm / min
Load cell: 50N
Number of tests: 5 times

(Measurement example 3: Water swelling rate measurement)
The water swelling rate of the obtained film made of the block copolymers of Reference Examples 1 to 14 is measured in order to further observe the characteristics of the film state. Specifically, the procedure is the same as in Measurement Example 2. The prepared strip-shaped (50 mm × 5 mm × 0.1 mm) film made of the block copolymers of Reference Examples 1 to 14 was placed in a plastic tube, and ion-exchanged water (15 mL) was added so that the entire film was immersed. After shaking this plastic tube for 3 hours in an incubator set at 37 ° C., the film was taken out and the long side length was measured. From the obtained long side length, the water swelling rate (%) of the film made of the block copolymers of Reference Examples 1 to 14 was calculated using the following formula 9. The results are shown in Table 1.

Water swelling rate (%) = (Lw-Ld) / (Ld) × 100 ・ ・ ・ Equation 9
Ld: Long side length (cm) when dried (before immersion in ion-exchanged water)
Lw: Long side length (cm) when wet (after immersion in ion-exchanged water)

(Reference Example 15: Preparation of Cylindrical Base Material A)
In the weaving process, the following warp threads (warp threads A and warp threads B) and weft threads (weft threads C and weft threads D) were used.
-Warp A (Kaijima composite fiber): Polyethylene terephthalate fiber, 66dtex, 9 filaments (after desealing treatment: 52.8dtex, 630 filaments)
-Warp B (dissolved yarn): Easy-alkali-soluble polyester fiber copolymerized with 5-sodium sulfoisophthalic acid, 84 dtex, 24 filaments-Weft C (inner layer) (Kaijima composite fiber): Polyethylene terephthalate fiber, 66 dtex, 9 filaments (After desealing treatment: 52.8dtex, 630 filament)
-Weft D (outer layer): Polyethylene terephthalate fiber, 56dtex, 18 filaments

At the time of weaving, the tension of the warp B is 0.9 cN / dtex, the tension of the warp A is 0.1 cN / dtex, and the weaving density after post-processing is warp A, 201 threads / inch (2.54 cm), weft C, A tubular woven fabric having an inner diameter of 3.3 mm having 121 threads / inch (2.54 cm), weft D, and 121 threads / inch (2.54 cm) was woven. The warp threads A and the warp threads B were arranged at a ratio of one warp thread B to three warp threads A. Further, the warp B is arranged between the weft C located in the inner layer and the weft D located in the outer layer.

Next, post-processing was performed by the following steps to obtain a tubular base material A.
(A) The hot water washing treatment conditions were carried out at a temperature of 98 ° C. and a time of 20 minutes.
(B) Preheat set A round bar having an outer diameter of 2.8 mm was inserted into a tubular woven fabric, both ends were fixed with wires, and heat treatment was performed. The treatment conditions were a temperature of 180 ° C. and a time of 5 minutes. The material of the round bar was SUS.
(C) De-sea treatment The warp A and weft C were desea-treated, and the warp B was dissolved and removed.
(C-1) Acid treatment Maleic acid was used as the acid. The treatment conditions were a concentration of 0.2% by mass, a temperature of 130 ° C., and a time of 30 minutes.
(C-2) Alkali treatment Sodium hydroxide was used as the alkali. The treatment conditions were a sodium hydroxide concentration of 1% by mass, a temperature of 80 ° C., and a time of 90 minutes.
(D) Heat set (first time)
A round bar having an outer diameter of 3.3 mm was inserted into a tubular woven fabric, and both ends were fixed with a wire or the like in a state of maximally compressed so as not to cause wrinkles in the warp direction, and heat treatment was performed. The treatment conditions were a temperature of 180 ° C. and a time of 5 minutes. The material of the round bar was SUS.
(E) Heat set (second time)
A round bar having an outer diameter of 3.3 mm was inserted into a tubular woven fabric, and both ends were fixed with a wire or the like in a state of being extended by 30% in the warp direction, and heat treatment was performed. The treatment conditions were a temperature of 170 ° C. and a time of 5 minutes. The material of the round bar was SUS.

(Reference Example 16: Preparation of Cylindrical Base Material B)
In the heat set (1st time) and heat set (2nd time), the outer diameter of the round bar used was changed from a round bar with an outer diameter of 3.3 mm to a round bar with an outer diameter of 3.0 mm, and then the heat set (2nd time). ), A tubular base material was prepared in the same manner as in Reference Example 15 except that both ends were fixed in a state of being extended by 30% in the warp direction and fixed with a wire without extending in the warp direction. A state base material B was obtained.

(Reference Example 17: Preparation of Cylindrical Base Material C)
As polyester fibers constituting the outer layer of the tubular base material, a monofilament having a single yarn fineness of 180 dtex (diameter 0.13 mm) and a multifilament having a single yarn fineness of 2.33 dtex and a total fineness of 56 dtex were prepared and woven. Occasionally, the multifilament was used for the warp and the monofilament was used for the weft. In addition, as the polyester fiber constituting the inner layer of the tubular base material, the sea component polymer is composed of polyethylene terephthalate copolymerized with 5-sodium sulfoisophthalic acid, and the island component polymer is composed of polyethylene terephthalate. A multifilament A'with a single yarn fineness of 7.3 dtex and a total fineness of 66 dtex was used at a ratio of island (mass ratio) = 20/80 and the number of island components was 70). This multifilament A'becomes multifilament A by the ultrafine treatment. This was used as a warp and a weft during weaving.

Using the above fibers, a multi-cylindrical woven fabric having an inner diameter of 3.3 mm was woven by a shuttle room and refined at 98 ° C. Next, the sea component of the above-mentioned sea-island composite fiber was completely leached by treatment with a 4% by mass aqueous solution of sodium hydroxide at 98 ° C., and the single yarn fineness of the multifilament A'was 0.08 dtex (single yarn diameter 2. 9 μm), ultrafine to a total fineness of 53 dtex. Next, it is dried at 120 ° C., a rod-shaped jig is inserted into the cylinder, and the heat is set in a tubular shape at 170 ° C., the weft density of the outer layer is 21 / 2.54 cm, and the weft density of the inner layer is 336. A book / 2.54 cm tubular substrate C was obtained.

(Reference Example 18: Preparation of Cylindrical Base Material D)
As polyester fibers constituting the outer layer of the tubular base material, a monofilament having a single yarn fineness of 108 dtex (diameter 0.11 mm) and a multifilament having a single yarn fineness of 2.33 dtex and a total fineness of 56 dtex were prepared and woven. Occasionally, the multifilament was used for the warp and the monofilament was used for the weft. Further, as a polyester fiber constituting the inner layer of the tubular base material, a multifilament having a single yarn fineness of 0.23 dtex (single yarn diameter 4.7 μm) and a total fineness of 33 dtex was prepared. This was used as a warp and a weft during weaving.

Using the above fibers, a multi-cylindrical woven fabric having an inner diameter of 3.3 mm was woven by a shuttle room and refined at 98 ° C. Next, it is dried at 120 ° C., a rod-shaped jig is inserted into the cylinder, and the heat is set in a tubular shape at 170 ° C., the weft density of the outer layer is 76 lines / 2.54 cm, and the weft density of the inner layer is 230. A book / 2.54 cm tubular substrate D was obtained.

The 20N load elongation rate (%), inner diameter (mm), and outer diameter (mm) of the tubular base materials A to D obtained by conducting the following measurement examples 4 to 9 on the tubular base materials A to D. ), The distance between the marked lines during compression L1 (mm), the distance between the marked lines during extension L2 (mm), the value of (L2-L1) / L1 of the tubular substrates A to D, the outer diameter a during compression, during extension Table 3 shows the values of the outer diameter b and (ab) / a, the inner surface roughness (μm), and the water permeability (mL / cm ² / min.) Under a pressure of 16 kPa. The mass ratio of the block copolymer provided in the tubular substrates A to D with respect to the mass of the tubular substrates A to D is less than 1% by mass.

The mass ratio of the block copolymer constituting the coated tubular body to the mass of the tubular substrate can be measured by the following method.

The coated tubular body is cut out so as to have a length of 0.5 cm in the long axis direction at three arbitrary locations of the coated tubular body, and the cut out coated tubular body is dissolved in an organic solvent. .. This solution is subjected to ¹ H-NMR measurement at room temperature using JNM-EX270 (manufactured by JEOL Ltd.). Based on each peak of ¹ H-NMR obtained, the ratio of the mass of the block copolymer to the mass of the tubular substrate is calculated. Specifically, in the case of ethylene terephthalate residues, the hydrogen atom of the benzene ring (chemical shift value: about 8.2 ppm) is a characteristic peak, so this is the molar ratio based on the integrated value with all signals. If it is a lactic acid residue, the hydrogen atom at the α-position (chemical shift value: about 5.2 ppm), which is a methine group, is a characteristic peak, so this is based on the integrated value with all signals. The molar ratio was calculated, and in the case of caprolactone residues, the hydrogen atom at the α-position, which is a methylene group (chemical shift value is about 2.3 ppm), is a characteristic peak, so this is the integrated value with all signals. In the case of glycolic acid residues, the hydrogen atom at the α-position (chemical shift value is about 4.8 ppm), which is a methylene group, is a characteristic peak, so this is the total signal. The molar ratio is calculated based on the integrated value of, and in the case of ethylene glycol residues, the four hydrogen atoms of the ethylene group (chemical shift value: about 3.6 ppm) are characteristic peaks. The molar ratio is calculated based on the integrated value with all signals.

From the molar ratio obtained as a result of the above, the mass ratio of the block copolymer provided in the tubular substrates A to D with respect to the mass of the tubular substrates A to D is calculated using the following formulas 10 and 11.
W _cop (%) = Mx _total / (M _ET × x _ET ) × 100 ・ ・ ・ Equation 10
Mx _total = M _EG x x _EG + M _LA x x _LA + M _CL x x _CL + M _GA x x _GA + M _PG x x _PG ... Equation 11

W _cop : Mass ratio of block copolymer provided on the tubular substrate to the mass of the tubular substrate M _ET : Molecular weight of ethylene terephthalate residue x _ET : Molar ratio of ethylene terephthalate residue

The organic solvent used is not particularly limited as long as it dissolves both the tubular substrate and the block copolymer, but 1,1,1,3,3,3-hexafluoroisopropanol-D2 is preferably used. ..

(Measurement example 4: 20N load elongation rate)
Cut the tubular base materials A to D so that the length in the major axis direction is 150 mm, and use the dual column desktop tester INSTRON5965 (manufactured by Instron Japan) so that the distance between the chucks in the major axis direction is 100 mm. Cylindrical substrates A to D were attached to the surface, and a tensile test was measured under the following condition B according to ISO7198 (2016). The elongation rate (%) of the tubular base materials A to D when a load of 20 N was applied was calculated from the following formula 12. The results are shown in Table 2.
(Condition B)
Equipment name: Dual column desktop testing machine INSTRON5965 (manufactured by Instron Japan)
Initial length: 100 mm
Tensile speed: 50 mm / min
Load cell: 1kN
Number of tests: 5 times

20N load elongation rate (%) = length (mm) of tubular base material when a load of 20N is applied / initial length (mm) x 100 ... Equation 12

(Measurement Example 5: Measurement of Inner Diameter and Outer Diameter of Cylindrical Bases A to D)
The inner diameters of the tubular base materials A to D were measured according to the guidance of ISO7198. Specifically, a cone with a taper degree of 1/10 or less is vertically erected, and the cylindrical base material is gently dropped vertically so as to cover a cross section cut in the radial direction, and the cone at the lower end position of the stopped sample is placed. The diameter of was measured. It was cut at intervals of 50 mm in the long axis direction, measurement was performed at 5 points, and the average value of the obtained measurement results was taken as the inner diameter (mm) of each of the tubular substrates A to D. Regarding the outer diameters of the tubular base materials A to D, the outer diameters were measured at 5 points in the major axis direction at intervals of 50 mm with no stress applied to the tubular base materials, and the measurement results obtained were obtained. The average value was taken as the outer diameter (mm) of each of the tubular base materials A to D. The results are shown in Table 2.

(Measurement example 6: Measurement of distance between marked lines L1 when compressed and distance L2 between marked lines when extended)
The distance between the marked lines during compression (mm) was measured from the outer diameters (mm) of the tubular base materials A to D in a state where no stress was applied to the tubular base material obtained in Measurement Example 5. FIG. 1 is an explanatory diagram for drawing a marked line on the tubular base material. As shown in FIG. 1, the first marked line 2 is drawn on the outer circumference of the base material 5 mm from one end of the tubular base material. The second marked line 3 is drawn on the outer circumference of the tubular base material at a distance A of 5 times the maximum outer diameter of the tubular base material from the first marked line. The tubular base material is cut in the radial direction at a position 5 mm from the second marked line.

FIG. 2 is a conceptual diagram of an apparatus for measuring the distance (mm) between the marked lines during compression of the tubular base materials A to D. As shown in FIG. 2, the apparatus has a HANDY DIGITAL FORCE GAUGE HF-1 (rated capacity 10N) manufactured by Nippon Measuring Systems Co., Ltd. installed on the gantry 5 as a load measuring device (force gauge) 4, and has a core rod portion. The compression chuck jig 6 having the above is attached to the load measuring device 4, and the compression receiving jig 7 having a hole into which the core rod portion can be inserted is attached to the gantry 5. The distance between marked lines L1 (marked when compressed) when the core rod portion of the compression chuck jig 6 is passed through the tubular base materials A to D and set in the above device and compressed with a stress of 0.01 cN / dtex in the long axis direction. The distance between lines) was measured with a caliper.

Here, the core rod portion of the compression chuck jig 6 to be inserted into the tubular base material 1 has an inner diameter of −0.1 mm (± 0.03 mm) of the tubular base material 1, and the compression receiving jig 7 The hole portion of is the same diameter as the inner diameter of the tubular base material. Here, the same diameter does not have to be exactly the same diameter, and a difference of about ± 0.03 mm is treated as the same diameter. Further, FIG. 3 is a conceptual diagram of a device for measuring the distance between the marked lines when the tubular base material is extended. As shown in FIG. 3, the device is used as a load measuring device (force gauge) 4. , HANDY DIGITAL FORCE GAUGE HF-1 (rated capacity 10N) manufactured by Nippon Measuring Systems Co., Ltd. is installed on the gantry 5, the extension chuck jig 8 is attached to the load measuring device 4, and the extension receiving jig 9 is attached to the gantry 5. It is attached to. The outside of the marked line of the tubular base material 1 is fixed with a fixing string 10, and the distance between the marked lines L2 (distance between the marked lines when extended) when extended with a stress of 0.01 cN / dtex in the long axis direction is determined by a caliper. It was measured. The results are shown in Table 2.

(Measurement Example 7: Measurement of outer diameter a during compression, outer diameter b during expansion, and values of (ab) / a)
The core rod portion of the compression chuck jig 6 shown in FIG. 2 is passed through the tubular base materials A to D and set in the apparatus shown in FIG. 2, and the tubular base materials A to D are set to 0.01 cN / dtex in the long axis direction. The outer diameter was measured with a caliper at 5 points in the long axis direction at intervals of 50 mm in the state of being compressed by the stress of ".
Further, the core rod portion of the compression chuck jig 6 shown in FIG. 2 is passed through the tubular base materials A to D and set in the apparatus shown in FIG. 2, and the tubular base materials A to D are 0.01 cN in the long axis direction. The outer diameter was measured with a caliper at 5 points in the long axis direction at intervals of 50 mm in a state of being stretched by the stress of / dtex, and the average value of the obtained measurement results was calculated as the "outside during stretching" of the tubular substrates A to D. Diameter b ”.

The value of (ab) / a was determined from the compressed outer diameter a of the obtained tubular base materials A to D and the extended outer diameter b of the tubular base materials A to D. The results are shown in Table 3.

(Measurement Example 8: Inner Surface Roughness of Cylindrical Base Material)
D _s and D _l of the inner surface of the tubular base materials A to D were measured based on a photograph obtained by magnifying the cross section of the tubular base materials A to D cut in the long axis direction by 150 times with an electron microscope. , The inner surface roughness was determined from the difference between D _s and D _l . FIG. 4 is an example of D _s and D _l . The measurement was performed 5 times with different fields of view, and the average value was evaluated. The average value was defined as "inner surface roughness of the tubular base material". The results are shown in Table 3.

(Measurement example 9: Water permeability)
Joints (manufactured by Isis) were attached to both ends of the tubular base materials A to D, and silicon tubes were connected. Water was flowed from one silicon tube so that a pressure of 16 kPa was applied to the inner surface of the tubular base material, while the other silicon tube was sandwiched between forceps to prevent water from flowing out from the silicon tube. In this state, run water for about 1 minute, measure the amount (mL) of water flowing out from the outer surface of the tubular base materials A to D, and measure this value as the area of the outer surface of the tubular base materials A to D. Water permeability (mL / cm ² / min.) Of the tubular substrates A to D under a pressure of 16 kPa was obtained from the values divided by (cm ² ) and the time (min.) Of flowing water. The results are shown in Table 3.

(Example 1)
A chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 1 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 1 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 2)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with two layers containing the double second polymer. As a result, the coated tubular body of Example 2 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 3)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 4. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 4 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 3 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 4)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 6, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 3. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 6 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 3 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 4 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 5)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 6, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 4. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 6 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 4 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 5 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 6)
A tubular body coated by the same method as in Example 1 was prepared except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 7. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 7 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 1 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 6 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 7)
A chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 8 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 1 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed three times, and the first polymer layer was coated with the triple second polymer layer. As a result, the coated tubular body of Example 7 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the triple second polymer layer was obtained.

(Example 8)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 13. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 13 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 8 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 9)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 11. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 11 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 9 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 10)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 14, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 14 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 10 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 11)
A chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The step of applying the first polymer solution to the tubular base material A made of polyethylene terephthalate fiber was performed three times, and the tubular base material A was coated with the triple first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed three times, and the first polymer layer was coated with the triple second polymer layer. As a result, the coated tubular body of Example 11 in which the tubular base material A was coated with the triple first polymer layer and the first polymer layer was coated with the triple second polymer layer was obtained.

(Example 12)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 12, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 12 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 12 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 13)
The tubular base material A was coated on the tubular base material B in the same manner as in Example 1 except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. A tubular body was created. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material B made of polyethylene terephthalate fiber, and the tubular base material B was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 13 in which the tubular base material B was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Example 14)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 14, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 4. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 14 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 4 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, the coated tubular body of Example 14 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 1)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 8. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 8 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 1 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 2)
Except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 6, and the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 6. Prepared a tubular body coated by the same method as in Example 1. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 6 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 6 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 2 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 3)
A tubular body coated by the same method as in Example 1 was prepared except that the first polymer was changed from the block copolymer of Reference Example 5 to the block copolymer of Reference Example 9. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 9 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 1 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 3 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 4)
A tubular body coated by the same method as in Example 1 was prepared except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 10. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material A made of polyethylene terephthalate fiber, and the tubular base material A was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 10 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 4 in which the tubular base material A was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 5)
The tubular base material A was coated with the tubular base material C in the same manner as in Example 1 except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. A tubular body was created. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material C made of polyethylene terephthalate fiber, and the tubular base material C was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 5 in which the tubular base material C was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

(Comparative Example 6)
The tubular base material A was coated with the tubular base material D in the same manner as in Example 1 except that the second polymer was changed from the block copolymer of Reference Example 1 to the block copolymer of Reference Example 2. A tubular body was created. Specifically, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 5 (first polymer solution). The first polymer solution was applied to the tubular base material D made of polyethylene terephthalate fiber, and the tubular base material D was coated with the first polymer layer. Next, a chloroform solution having a concentration of 20% by mass was prepared using the block copolymer of Reference Example 2 (second polymer solution). The step of applying the second polymer solution on the first polymer layer was performed twice, and the first polymer layer was coated with the double second polymer layer. As a result, a coated tubular body of Comparative Example 6 in which the tubular base material D was coated with the first polymer layer and the first polymer layer was coated with the double second polymer layer was obtained.

20N load elongation rate (%) and water swelling rate (%) were measured for the coated tubular bodies of Examples 1 to 14 and Comparative Examples 1 to 6 according to the methods of Measurement Examples 3 and 4, and the tubular body was formed. Table 4 shows the combination of the base material, the first polymer layer and the second polymer layer. Similarly, according to the methods described in Measurement Examples 10 to 14, the average layer thickness (μm), kink radius (mm), elongation rate when wet (%) and platelet adhesion number (%) were measured, and each Example and The results of the comparative example are shown in Table 5.

(Measurement example 10: Layer thickness measurement)
The coated tubular bodies of Examples 1 to 14 and Comparative Examples 1 to 6 were cut in the circumferential direction, and the thickness of the block copolymer layer in the cross section was measured by SEM. The measurement was performed 5 times with different fields of view, and the average value of the total layer thicknesses of the obtained first polymer layer and second polymer layer was taken as the average layer thickness (μm). The results are shown in Table 5.

(Measurement example 11: Kink resistance test)
A loop is formed under non-internal pressure on the coated tubular bodies of Examples 1 to 14 and Comparative Examples 1 to 6, and a tube having a radius of R (mm) is inserted into the loop, and the loop diameter is gradually increased. I made it smaller. It was confirmed whether the coated tubular body buckled before the loop diameter reached the tube diameter, and if it did not buckle, the kink radius of the covered tubular body was assumed to be R (mm) or less. .. The results are shown in Table 5.

(Measurement Example 12: Evaluation of extensibility and antithrombotic property when wet using porcine platelet-rich plasma (Pig PRP))
Citrate-added porcine blood was centrifuged at 130 g for 15 minutes, and the supernatant was collected. Physiological saline was added to the collected supernatant to obtain diluted PRP.

The coated tubular bodies of Examples 1 to 14 and Comparative Examples 1 to 6 were cut so that the length in the major axis direction was 3 cm, and joints (manufactured by Isis) were attached to both ends to set the test level.

The test level and the pump were connected with a silicon tube, the prepared circuit was filled with diluted PRP, circulated at room temperature for 30 minutes, the test level was taken out, and the length was measured. From the following formula 13, the elongation rate (%) of the coated tubular bodies of Examples 1 to 14 and Comparative Examples 1 to 6 when wet was calculated. The results are shown in Table 5.
Elongation rate when wet (%) = (D2-D1) / (D1) × 100 ・ ・ ・ Equation 13
D1: Length (cm) of the coated tubular body before the circulation test
D2: Length of covered tubular body after circulation test (cm)

Subsequently, the test level after circulation was punched with a biopsy trepan (φ6 mm) and washed 3 times with PBS (−).

Using the LDH Cytotoxicity Detection Kit (manufactured by Takara Bio Inc.), the number of platelets adhering to the test level after washing was calculated. At this time, relative comparison was performed between the other Examples and Comparative Examples, assuming that the number of platelets attached to the coated tubular body of Comparative Example 2 was 100%. The results are shown in Table 5.

(Measurement example 13: Evaluation of patency rate in dog transplantation experiment)
A canine transplantation test was performed using the coated tubular bodies of Examples 1-14 and Comparative Examples 2, 5 and 6. Ten cases of tubular body (3 cm) covered with end-to-end anastomosis were transplanted into the carotid artery, and three months after the transplantation, it was confirmed by echography whether or not it was patency.

Specifically, male beagle dogs were administered aspirin and dipyridamole from 2 days before transplantation to the day of excision. Isoflurane inhalation anesthesia was performed. After an incision was made in the neck to expose the carotid artery, heparin 100 IU / kg was intravenously administered to systemic heparinization. Blood flow was blocked and a covered tubular body (3 cm) was transplanted into the carotid artery by end-to-end anastomosis. Blood flow was resumed, the wound was closed, and the patient was awakened from anesthesia. Covered once a week until 1 month after transplantation, and once a month until 3 months after transplantation, using an echo device (digital ultrasonic diagnostic imaging device Noblue, Hitachi, Ltd.) to occlude by 3 months after transplantation. The number of tubular bodies was confirmed. From the results, the patency rate (%) was calculated using the following formula 14.
P = Np / Na × 100 ・ ・ ・ Equation 14
P: Patriotic rate (%)
Np: Number of coated tubular bodies that were patented up to 3 months after transplantation (lines)
Na: Number of transplanted coated tubular bodies (pieces)

Here, since it is generally said that long-term patency is possible if obstruction does not occur within 3 months after transplantation, the transplantation period was set to 3 months for the evaluation of the patency rate in the canine transplantation experiment.

Table 5 shows the patency rates (%) of the coated tubular bodies for implants of Examples 1-14 and Comparative Examples 2, 5 and 6.

The present invention can be suitably used for medical applications related to implants such as artificial blood vessels or stent grafts.

Claims (9)

A tubular base material having an elongation rate in the long axis direction of 5% to 100% under the condition of applying a tensile load of 20 N, and
A first polymer layer comprising a first polymer consisting of a polyalkylene glycol block and a polyhydroxyalkanoic acid block and having a mass ratio of alkylene glycol residues of 25% by mass to 60% by mass.
A second polymer layer comprising a second polymer consisting of a polyalkylene glycol block and / or a polyhydroxyalkanoic acid block and having a hydroxyalkanoic acid residue mass ratio of 75% by mass to 100% by mass.
With
The first polymer layer covers the tubular substrate and
The second polymer layer covers the first polymer layer and
The first polymer and the second polymer are tubular bodies for implants, each of which has a Young's modulus of 200 MPa or less when made into a film. The tubular body according to claim 1, wherein the polyalkylene glycol block contains an ethylene glycol residue and / or a propylene glycol residue. The tubular body according to claim 1, wherein the polyhydroxyalkanoic acid block contains a residue selected from the group consisting of a lactic acid residue, a glycolic acid residue and a caprolactone residue. The tubular body according to any one of claims 1 to 3, wherein the polyalkylene glycol block has a weight average molecular weight of 7,000 to 170,000. The tubular body according to any one of claims 1 to 4, wherein the tubular base material satisfies the following formula 1.
(L2-L1) / L1 ≧ 0.1 ・ ・ ・ Equation 1
L1: A marked line is drawn on the outer circumference of the tubular base material at a distance of 5 times the maximum outer diameter when measured without applying stress to the tubular base material, and the longitudinal direction of the tubular base material is long. Distance between marked lines when compressed with a stress of 0.01 cN / dtex L2: The distance of the tubular substrate is 5 times the maximum outer diameter when measured without applying stress to the tubular substrate. Distance between marked lines when a marked line is drawn on the outer circumference and extended in the long axis direction of the tubular base material with a stress of 0.01 cN / dtex. The tubular body according to any one of claims 1 to 5, wherein the tubular base material satisfies the following formula 2.
0.03 ≦ (ab) / a <0.2 ・ ・ ・ Equation 2
a: Outer diameter of the tubular base material when compressed with a stress of 0.01 cN / dtex in the long axis direction b: The tubular base material when stretched with a stress of 0.01 cN / dtex in the long axis direction Outer diameter The tubular body according to any one of claims 1 to 6, wherein the inner surface roughness of the tubular base material is 100 μm or less. An artificial blood vessel comprising the tubular body according to any one of claims 1 to 7. A stent graft comprising the tubular body according to any one of claims 1 to 7.

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