JPS6255426B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Technical Field The present invention relates to artificial blood vessels. Specifically, the present invention relates to an antithrombotic artificial blood vessel with a relatively small inner diameter. Prior Art While vascular diseases such as arteriosclerosis obliterans are on the rise, vascular surgical techniques have made significant progress in recent years, and vascular repair surgeries are being actively performed. In this case, a substitute blood vessel is used to maintain blood circulation in place of the diseased blood vessel. Substitute blood vessels are broadly classified into biological tissue blood vessels derived from living body vascular tissues and other living tissues, and artificial blood vessels derived from all artificial materials. Blood vessel substitutes include replacement grafts that are used as a supplement when a diseased blood vessel is removed;
It is used for bypass grafting, which is performed to bypass diseased blood vessels and support blood circulation. ) is often applied. The conditions necessary for such a blood vessel substitute are (a)
No denaturation in vivo, no toxicity, no foreign body reactions,
(b) Durable, (c) Free from carcinogenicity and antigenicity, (d) High elasticity and extensibility, resembling living blood vessels as much as possible, (e) Porous. (f) It has excellent antithrombotic properties; (g) It is easy to suture and the stump does not fray; (h) it is easy to disinfect and has resistance to infection; (i) it is easy to obtain materials in abundance. and (j) being inexpensive. A transplanted blood vessel substitute is a foreign substance to the living body, but in order to function stably as a conduit over a long period of time without being eliminated as a foreign substance, it must be adapted to the living body. It is necessary for the host to be taken up by the host. This transition to becoming a host occurs immediately after transplantation through deposition of blood components, thrombus, and fibrin membrane formation, followed by fibroplasma, pseudointernal formation, and fibrous adventitia formation. Conventionally, artificial blood vessels have been made of woven or knitted fabrics such as polyester (for example, Dacron (trade name)), polytetrafluoroethylene (for example, Teflon (trade name)), or polytetrafluoroethylene (for example, Teflon (trade name)). A porous polymer tube made by specially stretching fluoroethylene has been proposed. OBJECT OF THE INVENTION Therefore, an object of the present invention is to provide a novel artificial blood vessel. Another object of the present invention is to provide an artificial blood vessel with a small inner diameter that has excellent antithrombotic properties and good adhesion to living tissues surrounding the site where it is used. These objectives are to coat the inner surface of a flexible polymer tube with a tear strength of 20 kg/cm ² or more, elongation rate of 10% or more, and a synthetic fiber layer with an antithrombotic material, and coat the outer surface with collagen. Alternatively, it can be achieved by an artificial blood vessel characterized by being coated with gelatin. The present invention also provides an artificial blood vessel, wherein the flexible synthetic polymer tube has a synthetic fiber layer on the polyurethane tube. Further, the present invention is a vascular prosthesis, wherein the polyurethane tube is a segmented polyurethane tube. Further, the present invention provides an artificial blood vessel in which the synthetic fiber layer is formed by winding a woven fabric of nylon fibers in a spiral shape. Specific Structure of the Invention First, the artificial blood vessel according to the present invention is a flexible tube whose outer surface is coated with collagen or gelatin. In this method, a collagen or gelatin solution is applied once or several times at a concentration of 1 to 30% by weight, preferably 5 to 10% by weight, and then dried to obtain the desired artificial blood vessel. The film thickness is 1 to 1000 μm on a dry film thickness basis.
Preferably it is 0.1 to 1 mm. Note that among the above, collagen is particularly preferred. The inner diameter of the artificial blood vessel thus obtained is usually 6 mm or less, preferably 1 to 6 mm. The flexible tube has a tear strength of 20 kg/cm ² or more, preferably 30 kg/cm ² or more, and an elongation of 10% or more, preferably 20% or more. The flexible tube used in the artificial blood vessel according to the present invention includes a flexible polymer film or sheet tube manufactured by continuously extruding a polymer by extrusion molding or the like. Examples of such polymers include nylons such as nylon-6, nylon-6,6, and nylon-12; synthetic rubbers such as polyurethane, polytetrafluoroethylene, silicone rubber, chloroprene rubber, styrene-butadiene rubber, and nitrile rubber; There are natural rubber, synthetic or natural rubber latex, etc. Among these, materials with relatively high antithrombotic properties such as tetrafluoroethylene, silicone rubber, and polyurethane can be used as is, but in this case, other materials with low antithrombotic properties are also used. In such cases, it is desirable to coat the inner surface with a material with excellent antithrombotic properties as described below. Further, by reinforcing the flexible polymer tube with synthetic fibers, not only the mechanical strength is further increased, but also the stitchability is improved. The reinforcing synthetic fibers include a tubular body formed by spirally winding a synthetic fiber woven fabric, knitted fabric, etc., and a tubular body formed by spirally winding the synthetic fibers in the same direction or in the opposite direction. It's a tube. Examples of synthetic fibers include nylon, polyester, and spandex, with spandex being preferred. In order to form such a synthetic fiber-reinforced polymer tube, for example, the synthetic fibers are wound in a spiral shape with or without coating a predetermined polymer on a mandrel, and then a polymer liquid is applied to the mandrel to form the polymer tube. There is a method in which the synthetic fiber layer is impregnated and then dried. In this case, a molten polymer can be coated on the inner surface of the synthetic fiber layer to form a flexible reinforcing polymer tube. In addition, when impregnating a synthetic fiber layer with a polymer solution, it is not desirable that the synthetic fibers used be soluble in the solvent of the solution. In any case, if the synthetic fiber-reinforced polymer has low antithrombotic properties, it is desirable to coat the inner surface of the flexible tube with a material that has good antithrombotic properties. A material with excellent antithrombotic properties suitable for internal coating is a block copolymer obtained by polymerizing a hydrophilic linear polymer with a molecular weight of 1,000 to 20,000 at both ends of a hydrophobic linear polymer with a molecular weight of 1,000 to 20,000. is preferred, but a multi-block copolymer obtained by block copolymerization of the hydrophobic linear polymer and the hydrophilic linear polymer may also be used. The molecular weight of such a block copolymer is 10,000 to 100,000, preferably 20,000 to 100,000.
50000. Such a block copolymer has, for example, the general formula HX ₁ -SR ₁ NR ₂ CONHR ₃ NHCO-X ₂ -CONHR ₃ NHCOR ₂ NR ₁ S-X ₁ H () [However, in the formula, X ₁ is general formula (In the formula, R ₄ is a hydrogen atom or a methyl group; R ₅ is an alkylene group having 2 to 10 carbon atoms when m is 1; or an alkylene group having 2 to 3 carbon atoms when m is 2 to 10; Preferably, m is an alkylene group having 1 and 2 to 3 carbon atoms, and n is an integer of 10 to 500. X ₂ is a general formula (In the formula, R ₆ is a hydrogen atom or a methyl group, l is 10-
It is an integer of 1100. ) general formula (In the formula, p is an integer from 10 to 1000.), R ₁ is a hydrocarbon residue of a mercaptan having an amino group,
R ₂ is a hydrogen atom or a methyl group of the mercaptan residue, or R ₃ is a hydrocarbon residue of the diisocyanate. There is a block copolymer shown by Such block copolymers have the general formula (In the formula, R ₆ and l are as described above.) or the general formula
(In the formula, p is as described above.) A polymer having isocyanate groups at both ends obtained by reacting polystyrene represented by the formula (wherein p is as described above) with a diisocyanate in a solvent, (In the formula, R ₁ , R ₂ , R ₄ , R ₅ , m and n are as described above.) By adding a polymer having an amino group at one end, a polymer having no inert hydrogen group is added. Obtained by reaction in a solvent. Further, the block copolymer may be a multi-block copolymer of each of the above components. In this case,
It can be obtained by substituting a part of the polymer having an amino group at one end with a polymer having the same amino group at both ends in a polymer having the general formula. In any case, the ratio of hydrophilic linear polymer to hydrophobic linear polymer is 45 to 65
mol %, preferably 55 to 63 mol %. The acrylic acid or methacrylic acid derivative polymer having a hydroxyl group and used as the alkalic acid or methacrylic acid derivative chain in the present invention is used as a chain transfer agent in the presence of a mercaptan having one amino group in the molecule. It is synthesized by reacting an acrylic or methacrylic acid derivative with a predetermined functional group concentration, molar ratio, and temperature in a solvent. The acrylic acid or methacrylic acid derivative having a hydroxyl group used in the present invention has the general formula (In the formula, R ₄ represents a hydrogen atom or a methyl group, and R ₅ represents an alkylene group having 2 to 10 carbon atoms when m is 1 or 2 to 3 carbon atoms when m is 2 to 10.) It is indicated by. To give you a typical example, 2
-Hydroxyethyl acrylate, 2-hydroxypropyl acrylate, 3-hydroxypropyl acrylate, 2-hydroxybutyl acrylate, 3-hydroxybutyl acrylate, 4-
Hydroxybutyl acrylate, 5-hydroxypentyl acrylate, 6-hydroxyhexyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate,
Examples include 3-hydroxypropyl methacrylate, 2-hydroxybutyl methacrylate, 3-hydroxybutyl methacrylate, 4-hydroxybutyl methacrylate, 5-hydroxypentyl methacrylate, and 6-hydroxyhexyl methacrylate. Examples of chain transfer agents for mercaptans having at least one amino group in the molecule include 1-aminomethanethiol, 1-aminoethanethiol,
2-aminoethanethiol, 1-aminopropanethiol, 2-aminopropanethiol, 3-aminopropanethiol, 1-aminobutanethiol, 2-aminobutanethiol, 3-aminobutanethiol, 4-aminobutanethiol, 1- Methyl-2-aminoethanethiol, 1-methyl-
1-aminoethanethiol, 3-aminocyclopentadiene-1-thiol, 1-aminobenzenethiol, 2-aminobenzenethiol, 3-aminobenzenethiol, 1-aminomethylbenzenethiol, 2-aminomethylbenzenethiol, 3 -aminomethylbenzenethiol, 1-aminoethylbenzenethiol, 2-aminoethylbenzenethiol, 3-aminoethylbenzenethiol, etc. The amount of these chain transfer agents used is 1 to 10 parts by weight per 100 parts by weight of the acrylic acid or methacrylic acid derivative monomer having the hydroxyl group.
parts by weight, preferably 1.5 to 80 parts by weight. The molecular weight of the polymer can be controlled by the amount of chain transfer agent used, that is, the molar ratio to the monomer. Examples of organic solvents include methanol, ethanol,
n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, ethylene glycol monomethyl ether, ethylene glycol monomethyl ether, ethylene glycol monobutyl ether, dimethylformamide, dimethyl sulfoxide, hexaalkylphosphoramide, acetonitrile, propionitrile , benzonitrile, etc. These organic solvents are used in an amount of 100 to 100 parts by weight per 100 parts by weight of the acrylic acid or methacrylic acid derivative monomer having the hydroxyl group.
1000 parts by weight are used, preferably 150-500 parts by weight. As a polymerization initiator, tert-butyl peroctoate, benzoyl peroxide, isopropyl percarbonate, 2,4-dichlorobenzoyl peroxide, methyl ethyl ketone peroxide, cumene hydroperoxide, dicumyl peroxide, azobisisobutyronitrile and so on. These polymerization initiators are used in an amount of 0.01 to 30 parts by weight, preferably 0.05 to 20 parts by weight, based on 100 parts by weight of the hydroxyl group-containing acrylic acid or methacrylic acid derivative monomer. The polymerization reaction of acrylic acid or methacrylic acid derivatives having hydroxyl groups is carried out by adding a monomer, a chain transfer agent, and a polymerization initiator to the above-mentioned organic solvent.
It is carried out at a temperature of 200°C, preferably 55 to 150°C, for 10 minutes to 30 hours, preferably 0.5 to 25 hours. To recover the polymer from the reaction mixture polymerized in this way, the reaction mixture can be concentrated or removed from the reactor as is or diluted with an organic solvent, and then diluted with 10 to 50 volumes of ethyl Any method can be used, such as dropping the polymer dropwise into a poor solvent such as ether to precipitate the polymer, separating it, and then drying it. The obtained polymer having an amino group at one end is
Vapor Pressure Osometry
The number average molecular weight measured by Method) is approximately 1000 to approximately
20000 (the following number average molecular weights are from the same measurement method). In addition, acrylic acid or methacrylic acid derivatives having amino groups at both ends used in the production of multi-block copolymers have hydroxyl groups as a chain transfer agent due to the presence of disulfides having two amino groups in the molecule. is synthesized by reacting an acrylic acid or methacrylic acid derivative having the following under the same conditions as in the production of the acrylic acid or methacrylic acid derivative polymer having an amino group at one end. Such disulfides include bis-
(aminoethyl) disulfide, bis-(aminopropyl) disulfide, bis-(2-aminophenyl) disulfide, bis-(3-aminophenyl) disulfide, bis-(4-aminophenyl) disulfide, bis-(2-aminoethyl phenyl) ) disulfide, bis-(3-aminoethylphenyl) disulfide, bis-(4-aminoethylphenyl) disulfide, etc. The thus obtained polymer having amino groups at both ends has a number average molecular weight of about 1,000 to about 20,000. The polyalkylene oxide having isocyanate groups at both ends, which is used as a polyalkylene oxide chain by the method of the present invention, retains one functional group of the diisocyanate and the other.
Selective functional groups are added to polyalkylene glycol in an organic solvent at a predetermined functional group concentration, functional group ratio,
Synthesized by reacting at high temperatures. The polyalkylene glycol having hydroxyl groups at both ends used in the present invention has the following general formula: (In the formula, R ₆ is a hydrogen atom or a methyl group, R ₇ is an alkylene group having 1 to 3 carbon atoms, and l is 10 to
(representing an integer of 1100). Typical examples include polyethylene glycol and polypropylene glycol. By using reprecipitation or fractional precipitation of these polymers, any highly monodisperse fractional component having a molecular weight in the range of 1,000 to 20,000, preferably 5,000 to 10,000 can be obtained. Diisocyanates include aliphatic or aromatic diisocyanates, such as m-phenylene diisocyanate, p-phenylene diisocyanate, 1-chloro-2,4-phenylene diisocyanate, 2,4 -Tolylene diisocyanate,
2,6-tolylene diisocyanate, 3,3'-dimethyl-4,4'-biphenylene diisocyanate, 3,3'-dimethoxy-4,4'-biphenylene diisocyanate, 2,2', 5,5'-tetramethyl-4,4'-biphenylene diisocyanate,
Examples include 4,4'-methylenebis(phenyl isocyanate), 4,4'-methylenebis(2-methylphenylisocyanate), and 4,4'-sulfonylbis(phenyl isocyanate). The addition reaction of diisocyanates to the polymer is carried out in an organic solvent at a functional group concentration of 0.002 to 0.20 M with a ratio of isocyanate groups to hydroxyl groups of about 2:1, and at 60 to 120°C. , preferably at a temperature of 80 to 90°C for 20 to 75 hours, preferably 30 to 50 hours. Examples of organic solvents include chlorobenzene, toluene, xylene, and benzene. In the reaction mixture obtained in this way, unreacted diisocyanates almost disappear after a predetermined period of time, so further purification is necessary to avoid deactivation of isocyanate groups that occurs during reprecipitation purification. It can be used as is for the next reaction. In addition, polystyrene having isocyanate groups at both ends, which is used as a polystyrene chain,
While retaining one functional group of diisocyanates, the other functional group is selectively added to polystyrene,
It is synthesized by reacting under the same conditions as for the production of polyalkylene oxide chains. A polymer reaction between the obtained acrylic acid or methacrylic acid derivative polymer having an amino group at one end and/or both ends and a polyalkylene oxide or polystyrene having an isocyanate group at both ends is performed using the acrylic acid or methacrylic acid. The derivative polymer is N,N-dimethylformamide,
Mixing the reaction mixture of the polyalkylene oxide or polystyrene in a solvent without active hydrogen such as benzene, acetone, or THF at a functional group ratio of isocyanate groups to amino groups of about 1:1, Adjust to sensory concentration 0.002~0.2, -10~15℃
It is preferably carried out at a temperature of 0 to 10°C for 20 to 75 hours, preferably 30 to 50 hours. In order to recover the reaction mixture from the polymer-reacted reaction mixture in this way, the reaction mixture is diluted with an organic solvent, taken out from the reactor, and placed in 10 to 50 times the volume of a guest solvent such as ethyl ether. Drop into the
Any method can be used, such as precipitating the reaction mixture, separating it, and then drying it. The obtained block copolymer can be purified using a fractional precipitation method or a reprecipitation method. In this case, the fractional precipitation method takes advantage of the difference in temperature dependence of solubility between the two prepolymers and the block copolymer, and the reprecipitation method takes advantage of the temperature dependence of each prepolymer. This is a method in which the reprecipitation operation is repeated in a solvent in which the block copolymer is insoluble. The block copolymer obtained in this way is
It is an ABA type block copolymer or a multi-block copolymer such as ABA type as shown by the above general formula. Such block copolymers not only have a microphase-separated structure with hydrophilic and hydrophobic properties, but also have a hydrophilic portion with a
When it is 45 to 65 mol%, preferably 55 to 63 mol%, it forms a lamellar structure of about 200 to 5000 Å of hydrophilicity and hydrophobicity, and a sea-island structure with hydrophilicity as the sea, resulting in extremely excellent antithrombotic properties. It becomes something. Such a block copolymer can be coated on at least the inner surface of the flexible polymer tube when the tube is a polymer film or sheet tubular body. This is carried out by applying a solution of 1 to the inner surface or both surfaces thereof and then drying the coating, and the dry film thickness of the coating is 0.1 μm or more, preferably 1 to 500 μm. If the adhesion between the tube and the block copolymer coating is low, it is desirable to increase the adhesion by treating the surface of the tube with plasma treatment or the like. In addition, when the tube is made of synthetic fiber, after applying the block copolymer solution to the tubular or rod-shaped body, a belt-like woven or knitted fabric of synthetic fiber is wound in a spiral shape on the coated surface, and then It is obtained by coating the surface of the block copolymer solution to impregnate it into the fiber layer, and then drying it. Also,
When a synthetic fiber system is used, the system is spirally applied to the coating surface in one direction, or further spirally from the opposite direction so as to cross, and this is alternately repeated as necessary to form a fiber layer, It is obtained by coating the surface of the tubular fiber layer with the block copolymer solution to impregnate the fiber layer, and then drying it. Next, the present invention will be explained in more detail by giving Examples. First, a method for producing a polyalkylene oxide having isocyanate groups at both ends will be described in detail. Polymer A Polyethylene glycol with number average molecular weight 7110
100g and 2,4-toluene diisocyanate 4899
The volume was adjusted to 1400 c.c. with chlorobenzene, and the reaction was carried out at a temperature of 80° C. for 48 hours. The mixed solution before reaction has a functional group ratio of isocyanate groups to hydroxyl groups of approximately 2.
The functional group concentration was adjusted to about 0.02M/1. After the reaction was completed, analysis revealed that the number average molecular weight was 1.96 isocyanate groups per molecule.
7.460 polymer was obtained. The reaction rate was 98%. Polymer B Polyethylene glycol with a number average molecular weight of 1000
100g and 2,4-toluene diisocyanate 34830
Adjust the volume to 2000 ml with chlorobenzene and add polymer A.
The reaction was carried out in the same manner. The functional group ratio of the pre-reaction mixed solution is the same as that of polymer A, the functional group concentration is 0.1M/
I adjusted it so that A polymer with 1.98 isocyanate groups in one molecule and a number average molecular weight of 1350.
A reaction rate of 99% was obtained. Polymer C Polyethylene glycol with a number average molecular weight of 20,000
100g and 2,4-toluene diisocyanate 2.176
A reaction was carried out in the same manner as for Polymer A. The functional group ratio before the reaction was adjusted to be the same as that of Polymer A, and the functional group concentration was adjusted to 0.005M/. The number of isocyanate groups in one molecule is
1.96 polymers with a number average molecular weight of 16350 are 98
% reaction rate was obtained. Next, a method for producing a methacrylic acid derivative polymer having an amino group at one end will be described in detail. Polymer D 2-hydroxyethyl methacrylate in the polymerization tube
100gα,α′-azobisisobutyronitrile
0.252 g, 41.50 g of 2-aminoethanethiol, and 290.3 g of N,N-dimethylformamide were charged, sealed in a vacuum tube, and reacted for 8.5 hours while shaking in a constant temperature bath maintained at a temperature of 60°C. Ta. After the reaction was completed, the reaction mixture was diluted with acetone, taken out from the polymerization tube, and dropped into 20 times the volume of ethyl ether to precipitate the polymer. After separation, the polymer was dried in vacuum, and the amino group introduction rate per molecule was 1
Polymer with a number average molecular weight of 2640 in moles is 21.50%
was obtained in a yield of . Polymer E Reaction and purification were carried out under the same conditions as for Polymer D, except that 26.68 g of 2-aminoethanethiol was used and the reaction time was 5 hours. A polymer with a number average molecular weight of 5200 was obtained in a yield of 19.20%. Polymer F 2-aminoethanethiol 20.75g, reaction time
The reaction and purification were carried out under the same conditions as Polymer D except for 3.5 hours. A polymer with a number average molecular weight of 11270 was obtained with a yield of 24.33%. Polymer G 2-aminoethanethiol 4.02g, reaction time
Reaction and purification were carried out under the same conditions as for Polymer D except for 5.5 hours. A polymer with a number average molecular weight of 6400 was obtained in a yield of 25.93%. Polymer H 107 g of styrene and 7.5 g of p,p'-diisocyanate diphenyl disulfide were sealed in a quartz polymerization tube under vacuum and heated under mercury lamp irradiation for 12 hours.
The reaction was carried out at ℃. Further, purification was performed using tetrahydrofuran as a diluent and 20 to 50 times the volume of hexane as a reprecipitation solvent. A polymer having a number average molecular weight of 10,500 was obtained with a yield of 25.1%, and the number of isocyanate groups introduced into the molecule was 2.01. Polymer I Reaction and purification were carried out under the same conditions as for Polymer H except for 15 g of p,p'-diisocyanate diphenyl disulfide. A polymer with a number average molecular weight of 5500 was obtained in a yield of 19.4%. Next, a method for producing a block copolymer using polyalkylene oxide or polystyrene having isocyanate groups at both ends and acrylic acid or an acrylic acid or methacrylic acid derivative polymer having an amino group at one end will be described in detail. . Block copolymer A 100g of a chlorobenzene solution containing 7.1% by weight of Polymer A and 302g of N,N'-dimethylformamide containing 7.1% by weight of Polymer F were mixed, and the mixture was heated to 48% at a temperature of 0°C. A time polymer reaction was carried out.
The functional group ratio before the reaction was adjusted to be about 1:1 of isocyanate groups to amino groups, and the functional group concentration was 0.02 M/min. After the reaction was completed, the reaction solution was diluted with methanol, taken out from the reactor, and added dropwise to 20 times the volume of ethyl ether to precipitate the reaction mixture, separated and dried to recover the reaction mixture. This reaction mixture was added to ethyl cellosolve, heated and dissolved at a temperature of 50°C, and then cooled once to a temperature of 0°C to precipitate insoluble polymer A and block copolymer at a low temperature. Thereafter, the mixture was gradually heated to a temperature of 25°C, the block copolymer was dissolved at this temperature, and the mixture was separated using a centrifuge at a rotation speed of 5000 rpm to remove the precipitated unreacted polymer A. Ta. The supernatant liquid after centrifugation was gradually cooled to a temperature of 0°C again to precipitate the block copolymer, and then centrifuged at a rotation speed of 5000 rpm to remove unreacted polymer E dissolved at this temperature. It was separated and the precipitate was collected. The above separation operation was repeated twice, and the finally obtained precipitate was diluted with methanol, taken out, and dropped into 20 times the volume of ethyl ether to precipitate the block copolymer, separated and dried in vacuum. A block copolymer with a number average molecular weight of 30,000 was obtained in a yield of 76%. Block copolymers B to C Reactions and purification were carried out under the same conditions as for other block copolymers A shown in Table 1. Block Copolymers D to E The functional group ratio before reaction was adjusted to be about 1:1 of isocyanate groups to amino groups, and the concentration of functional groups was 0.02M/. After the completion of the reaction, the reaction solution was diluted with methanol or acetone, taken out from the reactor, and added dropwise to 20 times the volume of ethyl ether to precipitate the reaction mixture, separated and dried, and the reaction mixture was recovered. A block copolymer shown in the table was obtained.

[Table] Example 15 Segmented polyether urethane urea was deposited on a metal rod with a diameter of 2 mm from a 5% by weight dimethylacetamide solution, and after drying, a nylon fiber woven fabric (width: 5 mm, thickness: 0.1 mm) was wound into a spiral shape. to form a nylon fiber layer, and the segmented polyurethane urea solution is applied to the surface of the fiber layer, and the segmented polyurethane urea film is formed on both sides by depping and drying while impregnating the fiber layer. Ta. Next, a 1% by weight solution of block copolymers A to E in dimethylacetamide was poured onto the inner surface twice, and after drying, 10% by weight and 0.9% of collagen was applied to the outer surface.
A collagen coating was formed by applying a NaCl aqueous solution and drying it to obtain an artificial blood vessel with a length of 3 cm. Comparative Example 1 Comparative Example 1 was a case in which block copolymers A to E and collagen were not applied to the inner and outer surfaces of the artificial blood vessels obtained in Examples 1 to 5, respectively. Reference Example 1 The artificial blood vessels obtained in Examples 1 to 5 and Comparative Example 1 were anastomosed and connected to the resected portions of the aorta of five rabbits, and after 30 days, the inner surface of the blood vessels and After examining the outside, the results shown in Table 2 were obtained.

【table】

[Table] Examples 6 to 10 Artificial blood vessels were obtained in the same manner as in Examples 1 to 5 except that a metal rod with a diameter of 3 mm was used. Comparative Example 2 Artificial blood vessels were obtained in the same manner as in Comparative Example 1 except that a metal rod with a diameter of 3 mm was used. Reference Example 2 Using the artificial blood vessels obtained in Examples 6 to 10 and Comparative Example 2, parts of the aorta of three dogs were connected by anastomosis to the resected portions, and 10 days later, the inside and outside of the blood vessels were connected. When both sides were examined, the results shown in Table 3 were obtained.

【table】

[Table] Comparative example
2 Completely occluded Surrounding tissue
(In 3 hours, the blood will adhere to the weave.)
Plug formation) Specific effects of the invention As stated above, the present invention has a tear strength of 20 kg/
It is an artificial blood vessel made by coating an antithrombotic material on the inner surface of a flexible tube having a cm ² or more and an elongation rate of 10% or more and having a synthetic fiber layer, and coating the outer surface with collagen or gelatin. The artificial blood vessel has excellent adhesion to the living tissue surrounding the site where it is used, and therefore there is no fear of it slipping off even when used for a long period of time. The effect is especially great when collagen is used. Further, since a flexible tube having the above-mentioned physical properties is used as the base material, there is an advantage that it is durable, has high elasticity and extensibility, and is easy to suture. Moreover, since the flexible tube is made of a synthetic fiber-reinforced flexible polymer film or sheet, it has high mechanical strength and excellent stitchability.

Claims (1)

[Scope of Claims] 1. A tube made of a flexible polymer having a tear strength of 20 kg/cm ² or more and an elongation rate of 10% or more and having a synthetic fiber layer, the inner surface of which is coated with an antithrombotic material, and the outer surface An artificial blood vessel characterized by being coated with collagen or gelatin. 2. The artificial blood vessel according to claim 1, wherein the flexible synthetic polymer tube has a synthetic fiber layer on the polyurethane tube. 3. Claim 2, wherein the polyurethane tube is a segmented polyurethane tube.
Artificial blood vessels described in section. 4. The artificial blood vessel according to claim 2 or 3, wherein the synthetic fiber layer is a spirally wound nylon fiber woven fabric.