WO2012115275A1 - Prothèse vasculaire - Google Patents

Prothèse vasculaire Download PDF

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Publication number
WO2012115275A1
WO2012115275A1 PCT/JP2012/055151 JP2012055151W WO2012115275A1 WO 2012115275 A1 WO2012115275 A1 WO 2012115275A1 JP 2012055151 W JP2012055151 W JP 2012055151W WO 2012115275 A1 WO2012115275 A1 WO 2012115275A1
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Prior art keywords
blood vessel
artificial blood
pau
aromatic polyester
urethane resin
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PCT/JP2012/055151
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English (en)
Japanese (ja)
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慎治 内田
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Uchida Shinji
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Publication of WO2012115275A1 publication Critical patent/WO2012115275A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels

Definitions

  • the present invention relates to an artificial blood vessel, and particularly to an artificial blood vessel having excellent biocompatibility and safety.
  • a polyethylene terephthalate fiber (PET fiber) knitted fabric, a woven fabric tubular material, or a polytetrafluoroethylene stretched porous resin (e-PTFE) tubular material is used as the artificial blood vessel.
  • PET fiber polyethylene terephthalate fiber
  • e-PTFE polytetrafluoroethylene stretched porous resin
  • knitted PET fibers and tubular fabrics form a thrombus layer when blood flows, and endothelial cells are formed on the thrombus layer.
  • PET fibers are biocompatible, living cells invade from the outer wall of the blood vessel and reach new endothelial cells.
  • a fine blood vessel enters from the outer wall of the blood vessel and reaches a neovascular endothelial cell membrane generated in the blood vessel, and the thrombus is absorbed into the body with time.
  • the neointima in the blood vessels is metabolized by the blood flow of the small blood vessels, and is constantly maintained and managed as new.
  • the artificial intravascular neovascular membrane generated in this way has the same structure and function as a biological blood vessel, and is therefore an artificial blood vessel that is excellent in patency.
  • an artificial blood vessel using e-PTFE is PTFE (polytetrafluoroethylene), which is a typical non-biocompatible (biologically inert) substance
  • PTFE polytetrafluoroethylene
  • biological blood vessel biological blood vessel
  • the endothelial cell membrane enters from the living blood vessel toward the anastomosis part, but the invasion power of living cells from the outer wall of the blood vessel is very large even if the hole of e-PTFE is increased.
  • fine blood vessels do not invade, artificial blood vessels having a structure similar to biological blood vessels are not generated in artificial blood vessels like artificial blood vessels based on PET fibers.
  • the endothelial cell membrane that invades from the blood vessels toward the anastomosis part is difficult to adhere to e-PTFE, and even if it adheres, it peels off to form a hematoma, and this part becomes thickened over a long period of time. This causes stenosis in the part and causes obstruction.
  • e-PTFE is a biologically inert substance, so that blood coagulation does not occur as in the case of PET fibers, and the patency state remains for a certain period of time. Retain, but long-term patency cannot be expected.
  • an artificial blood vessel that is finally absorbed in the living body has been studied, but in the process where a biological blood vessel is formed in the artificial blood vessel and the artificial blood vessel is absorbed, It is said that it will gradually swell due to the internal pressure that is constantly applied to form an aneurysm and eventually rupture.
  • Patent Document 1 shows that PAU made a tube having an inner diameter of 1.0 mm and a length of 10 mm and transplanted into the abdominal aorta of a rat, and was bred for one week. Yes.
  • Example 4 of Patent Document 2 an anti-thrombotic material that can be used for a cell culture membrane, an inner diameter of 1.5 mm and a 7 mm e-PTFE human T-vessel coated with PAU, is transplanted into a rat abdominal aorta, and e -It has been shown that antithrombogenicity is improved compared to PTFE artificial blood vessels.
  • Non-Patent Document 1 when an e-PTFE artificial blood vessel having an inner diameter of 1.5 mm is coated with PAU and transplanted to the abdominal aorta of a rat, thrombus does not occur at all, and endothelial cells are well infused on the inner surface of the artificial blood vessel. This is explained by reactions with endothelial cell markers, electron micrographs, and optical micrographs.
  • the e-PTFE artificial blood vessel is inactive in the living body, the invasion property of the living cell from the outer wall of the blood vessel is poor, and it is difficult for the fine blood vessel to reach the blood vessel from the outer wall of the blood vessel.
  • Biological blood vessels that can be metabolized, such as fiber artificial blood vessels, are not generated.
  • Patent Document 3 proposes that a polyamino acid urethane resin (PAU) is used as a cell adhesion layer in a tube made of bioabsorbable aliphatic polyester fibers such as polyglycolic acid and polylactic acid.
  • PAU polyamino acid urethane resin
  • Patent Document 4 describes that PAU is bioabsorbable.
  • Patent Document 5 “at least the inner surface of a porous tubular structure is provided with (1) a polyamino acid urethane resin copolymer, (2) collagen or gelatin, and (3) an endothelial cell proliferation promoter having collagen binding activity. ”, An artificial blood vessel formed by sequentially laminating and fixing”.
  • the porous tubular structure used here it is described that polyethylene terephthalate, polybutylene terephthalate and the like can be used in addition to e-PTFE.
  • This artificial blood vessel is made by coating a porous tubular structure with polyamino acid urethane (PAU), coating with collagen or gelatin, and then laminating and coating an endothelial cell growth agent (endothelial cell growth factor).
  • PAU polyamino acid urethane
  • endothelial cell growth factor examples include other in vivo substances such as HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor).
  • HGF hepatocyte growth factor
  • VEGF vascular endothelial growth factor
  • the present invention is a method for producing an antithrombotic artificial blood vessel by producing an endothelial cell membrane by the endothelial cell proliferation action of PAU by flowing blood directly in contact with the PAU coating surface. Completely different.
  • Patent Document 5 uses PAU as an adhesive for immobilizing endothelial cell proliferating agents such as HGF and VEGF on the inner surface of an artificial blood vessel, whereas the present invention uses PAU itself as an endothelium. It is used as a cell proliferating agent.
  • An object of the present invention is to use an artificial polyester fiber made by a reaction of an aromatic dicarboxylic acid and an aliphatic diol, such as a PET fiber that is not easily decomposed or absorbed in vivo, or a polybutylene terephthalate fiber.
  • a thrombus is not generated when a blood vessel is connected to a living body blood vessel, and an artificial blood vessel that does not occlude for a long time is provided even in a small-diameter artificial blood vessel having an inner diameter of 6 mm or less.
  • a thrombus layer at a branched portion, a bent portion, or in some cases, an anastomosis portion is thick. Therefore, it is possible to provide a highly safe artificial blood vessel.
  • the uppermost layer on the inner surface of a tubular product obtained by coating or impregnating a polyamino acid urethane resin (PAU) on a tubular product based on a knitted fabric, a woven fabric, and a nonwoven fabric of an aromatic polyester fiber.
  • PAU polyamino acid urethane resin
  • the present invention can also be applied to an artificial blood vessel in which an aromatic polyester fiber base material is clogged with gelatin, collagen or the like.
  • FIG. 1 shows the process after transplantation of a conventional aromatic polyester fiber-based artificial blood vessel when an artificial blood vessel is transplanted (biological results are connected to both ends of the artificial blood vessel to cause blood flow).
  • FIG. 2 shows a course after transplantation of an artificial blood vessel in which a blood vessel is coated with PAU (a course after transplantation of a PAU-coated aromatic polyester fiber artificial blood vessel).
  • FIG. 3 shows a structure diagram of a biological blood vessel generated in an artificial blood vessel of an aromatic polyester fiber-based artificial blood vessel and a PAU-coated aromatic polyester fiber.
  • the blood vessel of the conventional aromatic polyester fiber shown in FIG. 1 when blood is passed through an artificial blood vessel having an inner diameter of 7 mm or more and clogged with only gelatin or collagen, the blood condenses on the tube wall. Since the thickness is about 2 mm or less, the blood vessel does not occlude, and the endothelial cell membrane covers the coagulated blood (thrombus layer) to form a surface structure similar to that of a biological blood vessel, and the fiber gap from the outer wall of the artificial blood vessel Incorporation of living cells and microvessels, smooth muscle cell layers under the endothelial cell layer, and formation of fibroblasts under them promotes integration with living tissue, creating artificial blood vessels that can withstand long-term use. It is formed. However, the thrombus layer may become thicker and occluded at the branched portion, the bent portion, and in some cases, at the anastomosis.
  • the blood vessel is blocked by the thickness of the thrombus layer generated by the patient's blood.
  • a thrombus does not occur, even in the case of an artificial blood vessel having an inner diameter of 7 mm or more, a thrombus may be generated in a branched portion, a bent portion, and in some cases, an anastomosis portion like a conventional artificial blood vessel of aromatic polyester fiber. It is a highly safe artificial blood vessel.
  • PAU is coated on an aromatic polyester fiber product (woven fabric, knitted fabric, non-woven fabric, etc.), a product with good touch and texture can be obtained.
  • the cause of this phenomenon is thought to be due to the eclectic action of the relatively antithrombogenic urethane segment in the PAU component and the peptide segment having an endothelial cell generating action.
  • the artificial blood vessel of the present invention has an effect that it does not occlude for a long time even if it has a small diameter of 6 mm or less.
  • a thick thrombosis layer is formed at the bent portion of an artificial blood vessel and, in some cases, the anastomosis portion, of a conventional aromatic polyester (PET) fiber that has been put to practical use.
  • PET aromatic polyester
  • the aromatic polyester fiber of the present invention is a polyethylene terephthalate (PET) fiber or a polybutylene terephthalate fiber obtained by fiberizing a reaction product of an aromatic dicarboxylic acid and an aliphatic diol. Mixtures of fibers or mixtures of these fibers with other fibers can be used.
  • PET polyethylene terephthalate
  • polybutylene terephthalate fiber obtained by fiberizing a reaction product of an aromatic dicarboxylic acid and an aliphatic diol. Mixtures of fibers or mixtures of these fibers with other fibers can be used.
  • the starting amino acid used in the PAU in the present invention may be any of an optically active substance, a racemate, or a mixture thereof.
  • a polyamino acid is a structure in which an average of 4 or more amino acid units are continuously bonded, and means a structure in which an average of 4 or more amino acids of the same or different types are continuously bonded. There are roughly two methods for synthesizing such a copolymer of polyamino acid and urethane.
  • the first method is a method in which polyamino acid and polyurethane are synthesized separately and then copolymerized.
  • This method is a method of reacting urethane with a polyamino acid obtained by polymerizing an active monomer as a polyamino acid synthesized by sequentially combining amino acids or a precursor of polyamino acid. In this method, it is difficult to increase the molecular weight of the polyamino acid or copolymer.
  • the second method is a method of copolymerizing an active monomer (polymerizable monomer) as a precursor of polyamino acid and urethane.
  • an active monomer polymerizable monomer
  • ⁇ -amino acid-N-carboxylic acid anhydride is used as a polyamino acid precursor in this method, it is easy to increase the molecular weight of both the polyamino acid chain in the copolymer to be produced and the copolymer. is there.
  • the polyamino acid urethane resin used in the present invention is obtained by this second method, that is, (a) an ⁇ -amino acid-N-carboxylic acid anhydride, (b) a urethane prepolymer having an isocyanate group at the terminal, and ( c) It is preferably formed of a polyamino acid urethane resin obtained by reacting at least one selected from water, hydrazine and organic amine.
  • amino acids used include neutral amino acids having 2 to 12 carbon atoms such as glycine, alanine, leucine, isoleucine, valine, ⁇ -aminoheptanoic acid, ⁇ -benzylaspartic acid, ⁇ -methyl-L- Monoesterified acidic amino acids such as glutamate, ⁇ -methyl-D-glutamate, and ⁇ -benzyl-L-glutamate, and ⁇ -amino groups such as ⁇ -acyllysine and ⁇ -acylortinin are protected with an appropriate masking group. Examples thereof include ⁇ -diaminocarboxylic acid derivatives and O-acetylleonine. In this case, the racemic or optically active form can be used as the ⁇ -amino acid.
  • N-carboxylic acid anhydride is abbreviated as NCA
  • NCA N-carboxylic acid anhydride
  • all of the above ⁇ -amino acids-NCA can be used. It is. Typical examples include glycine-NCA, alanine-NCA, leucine-NCA, and ⁇ -methyl-L-glutamate-NCA.
  • the urethane prepolymer having an isocyanate group at the terminal is obtained by reacting a polyisocyanate compound and a polyol under the condition of an equivalent ratio NCO / OH> 1.
  • a polyisocyanate component aromatic diisocyanate, aliphatic diisocyanate and alicyclic diisocyanate are used alone or as a mixture thereof.
  • polyether polyol examples include polyether polyol and polyester polyol alone or a mixture thereof.
  • polyether polyols include polypropylene ether glycol, polyethylene polypropylene ether glycol, polytetramethylene ether glycol, polypentamethylene ether glycol, polyethylene polytetramethylene ether random copolymer, polyethylene polytetramethylene ether block copolymer alone or Examples thereof include a glycol having an aromatic ring obtained by adding propylene oxide or ethylene oxide to bisphenol A and a mixture thereof.
  • polyester polyols include polycaprolactone polyols or those obtained by reaction of diols such as ethylene glycol and 1,4-butanediol with dibasic acids such as adipic acid and sebacic acid.
  • diols such as ethylene glycol and 1,4-butanediol
  • dibasic acids such as adipic acid and sebacic acid.
  • special polyols such as polyols obtained by adding caprolactone to polytetramethylene ether polyols or polypropylene ether polyols, and polysiloxane polyols can be used.
  • polycarbonate polyol obtained by deethanol reaction by adding excess molar ratio of 1,6-hexanediol or 3-methylpentanediol to diethylene carbonate is used.
  • polyether polyols preferably have a number average molecular weight of 200 or more.
  • the water used in the present invention means ordinary water and may be tap water, non-demineralized water, or demineralized water.
  • Hydrazine may be either anhydrous hydrazine or hydrous hydrazine, and hydrous hydrazine is industrially more advantageous in terms of safety.
  • organic amines include tertiary amines such as trimethylamine, triethylamine and tripropyldiamine, secondary diamines such as piperazine, primary diamines such as ethylenediamine, 1,3-propanediamine and 1,4-butanediamine, Suitable are primary and secondary amines such as 2-propanediamine and 1,3-butanediamine, and dihydrazides having a hydrantoin ring, such as 1,3-bis (hydrazidecarboethyl) -5-isopropylhydantoin.
  • hydrazine can be used.
  • the weight ratio of the ⁇ -amino acid NCA and the urethane prepolymer in obtaining the polyamino acid urethane resin is 5:95 to 95: 5, preferably 10:90 to 90:10, and more preferably 20:80. It is in the range of ⁇ 80: 20. This weight ratio is determined according to the desired antithrombogenicity, endothelial cell adhesion and mechanical properties.
  • the amount of hydrazine and the organic amine having primary or secondary active hydrogen is preferably at least 1/2 equivalent, more preferably at least 2/3 equivalent, based on the isocyanate group of the urethane prepolymer as an amino group.
  • the amount of tertiary amine used is preferably 1/1000 mol or more of ⁇ -amino acid NCA.
  • the polyamino acid urethane resin in the present method is obtained by reacting an ⁇ -amino acid-N-carboxylic acid anhydride, a urethane prepolymer having an isocyanate group at the terminal, and water, hydrazine or an organic amine in an organic solvent.
  • organic solvent used herein examples include chlorinated aliphatic hydrocarbons such as dichloromethane, 1,2-dichloroethane, 1,1,2-trichloroethane, chloroform, 1,1,2,2-tetrachloroethane, and benzene.
  • Aromatic hydrocarbons such as toluene and xylene
  • chlorinated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene
  • acetates such as ethyl acetate and butyl acetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, etc.
  • Water-soluble organic solvents that do not contain active hydrogen such as ketones, dimethylformamide, diethylformamide, dimethylacetamide, N-methylpyrrolidone, ethylene carbonate, dimethylsulfoxide, dioxane, tetrahydrofuran, hexamethylphosphoramide, or the like seed Including mixtures of the above.
  • the amount of the organic solvent used is such that the resin concentration in the polyamino acid urethane resin liquid of the final product is usually in the range of 3 to 50% by weight, preferably in the range of 10 to 30% by weight in terms of the produced resin solution. It is good to do. If the concentration is too high, the viscosity becomes remarkably high and a gel is formed. When the tube is coated or impregnated and processed, it may be diluted with a solvent, but it is difficult to handle. On the other hand, if the concentration is too low, it is difficult to obtain a product having a high viscosity (10,000 cps or more), and the versatility is poor.
  • the reaction temperature when producing a polyamino acid urethane resin liquid is preferably a temperature at which a single polymer having a high molecular weight can be synthesized from ⁇ -amino acid NCA.
  • a range of 60 ° C. is good.
  • the amino acid chain hardly takes an ⁇ -helix structure at the time of copolymerization, so that the degree of polymerization of the amino acid chain does not increase and a high molecular weight product may not be obtained.
  • the isocyanate group may undergo a burette reaction with the urea bond generated by the reaction between the isocyanate group and the amino group, thereby causing gelation.
  • the ⁇ -amino acid NCA and the urethane prepolymer have a weight ratio of, for example, 5:95 to 15: In the range of 85, the solution becomes relatively less turbid, and as the ratio of ⁇ -amino acid NCA increases, the turbidity increases, and a solution having an arbitrary viscosity within the range of 10 cps to 1 million cps / 25 ° C. is obtained. .
  • a method for obtaining a polyamino acid urethane resin (i) a method in which a urethane prepolymer and an ⁇ -amino acid NCA are mixed in the organic solvent and then a tertiary amine is added and reacted. (B) A method in which an ⁇ -amino acid NCA and a urethane prepolymer are mixed in the organic solvent, and then an organic amine having water, hydrazine or active hydrogen is added and reacted.
  • (C) A method in which a urethane prepolymer and an ⁇ -amino acid NCA are mixed in the organic solvent, an organic amine having water, hydrazine or active hydrogen is added and reacted, and then a tertiary amine is further added and reacted.
  • (D) A method in which a urethane prepolymer and water, hydrazine or an organic amine having active hydrogen are reacted in the organic solvent, and then ⁇ -amino acid NCA is added and reacted.
  • (E) A method of mixing an ⁇ -amino acid NCA and a urethane prepolymer in the organic solvent, then adding water, hydrazine, or an organic amine having active hydrogen to react, and further adding a urethane prepolymer.
  • (F) After reacting the urethane prepolymer with water, hydrazine, or an amine having active hydrogen in the organic solvent, ⁇ -amino acid-N-carboxylic acid anhydride is added and reacted, and then water is added. And a method of adding and reacting hydrazine or amines having active hydrogen.
  • PAU polyamino acid urethane resin
  • the type of the organic solvent is adapted to the use of PAU and the type of raw material ( ⁇ -amino acid NCA, urethane prepolymer).
  • a polyamino acid urethane resin obtained by the above method can be used by mixing a polyamino acid or a polyurethane resin.
  • the artificial blood vessel of the present invention can be obtained by coating or impregnating a polyamino acid urethane resin obtained by the above-mentioned method with a polyamino acid urethane resin on a knitted, woven or non-woven tubular article of an aromatic polyester fiber.
  • the concentration of the PAU solution is preferably 5% by weight or more when the tubular product of the aromatic polyester fiber that is not clogged with gelatin or collagen is immersed and impregnated in the PAU solution.
  • the concentration of the PAU solution when an artificial blood vessel is obtained by coating or impregnating a polyamino acid urethane resin with the above-mentioned tubular product of aromatic polyester fiber clogged with gelatin or collagen is preferably 1% or more, preferably 3 wt. % Or more.
  • an artificial blood vessel made of polyamino acid urethane resin PAU
  • PAU polyamino acid urethane resin
  • the amino acid content in the PAU is constant.
  • endothelial cells enter the artificial blood vessel, in addition to the invasion of living blood vessels, the uptake and growth of endothelial cells or endothelial cell-forming factors from blood by PAU resin, and the fine blood vessels from the artificial blood vessel outer wall to the artificial blood vessel
  • the endothelial cell membrane adheres and spreads throughout the artificial blood vessel when it enters the artificial blood vessel and opens in the artificial blood vessel. In this way, the formation of a biological blood vessel starts in the artificial blood vessel.
  • the artificial blood vessel is entirely covered with the endothelial cell membrane, there is no vascular occlusion due to the removal of the pannunu from the thrombus or the anastomosis, and there is a smooth muscle cell layer below the endothelial cell membrane, and below that Fibroblasts are created, and biological blood vessels are smoothly generated in the artificial blood vessel.
  • the PAU component, gelatin, collagen, etc. in the artificial blood vessel are gradually absorbed into the living body, and finally the living blood vessel is inserted into the gap between the knitted or woven fiber aggregates constituting the aromatic polyester fiber tube. Is formed. It is reported in the said patent document 4 that PAU is bioabsorbable.
  • the amino acid content in the PAU is 5 to 95%, preferably 10 to 90%, more preferably 15 to 85%.
  • amino acids other than ⁇ -amino acid NCA those according to this range are preferred.
  • polyamino acid urethane resin 980 g of polytetramethylene ether glycol (OH value 57.25) and tolylene diisocyanate (a mixture of 2,4-tolylene diisocyanate and 2,6-tolylene diisocyanate, 2,4 -Tolylene diisocyanate 80 wt%) 174 g was reacted at 70 ° C. for 5 hours to obtain a urethane prepolymer having an isocyanate group at the terminal (NCO equivalent, 1164).
  • the average degree of polymerization of amino acid chains in this solution is the reactivity of primary amines and isocyanates and the mechanism of NCA polymerization by primary amines (Murray Goodman and John Hutchison. J. Am. Chem. Soc., 88, 3627 (1966). )) To calculate approximately 62.
  • the metal rod was taken out, and the artificial blood vessel (sample 1) clogged with the polyamino acid urethane resin was obtained.
  • This artificial blood vessel had a dry touch and good tactile sensation.
  • an artificial blood vessel was obtained in which PAU was considered to have good fitting properties to a living body from a combination of an amino acid and urethane. This thing was made into the artificial blood vessel for biological experiment.
  • Comparative Example 1 B Preparation of urethane resin A solution in which 1.25 g of hydrazine hydrate was dissolved in 80.5 g of DMF, and 52.8 g of the same urethane prepolymer used in Example 1 was dissolved in 58.2 g of DMF under a nitrogen atmosphere. Were dropped and reacted to obtain a urethane resin solution (B) having a viscosity of 14,000 cps / 25 ° C. (concentration, 28 wt% DMF solution).
  • Example 2 Manufacture of artificial blood vessel
  • the urethane resin solution (B) was diluted with DMF to a concentration of 10 wt% as in Example 1, and immersed in this solution through a metal rod in the same tubular product (a) as in Example 1. After impregnating with the urethane resin solution, it was taken out and put into squeezed water with a roll to remove DMF. Next, this was air-dried, the metal rod was taken out, and an artificial blood vessel (sample 2) clogged with urethane resin was obtained. This artificial blood vessel had a rubber-like and sticky feel. This sample was used as a sample for a biological experiment for a comparative example.
  • the tubular product (a) used in Example 1 was clogged with collagen to produce a tubular product (b) from which leakage of blood was eliminated, and a metal rod was passed through the tube.
  • the polyamino acid urethane resin solution (A) (concentration 20 wt%) obtained in Example 1 was diluted with dichloroacetic acid to a concentration of 5 wt%, and a tubular material (b) passed through a metal rod was added thereto, and the concentration was 5 wt%. % Solution was impregnated.
  • Comparative Example 2 The tubular product (b) obtained by clogging the tubular product (a) used in Example 1 with collagen was used as an artificial blood vessel (sample 4). This was used as a comparative biological experiment sample.
  • the polyamino acid urethane resin (A) synthesized in Example 1 was diluted with DMF to obtain a concentration 10 wt% DMF solution.
  • a metal rod is passed through a tube of a tubular product (c) knitted from polyethylene terephthalate fiber having an inner diameter of 1.5 mm and a length of 10 mm, which is immersed in the polyamino acid urethane resin 10 wt% DMF solution, and the resin The solution was impregnated. Next, this was taken out from the solution and put into squeezed water with a roll to remove DMF.
  • Comparative Example 3 The urethane resin solution synthesized in Comparative Example 1 was diluted with DMF to a concentration of 10 wt%. Next, a metal rod is passed through a tube of a tubular product (c) formed by knitting polyethylene terephthalate fibers having an inner diameter of 1.5 mm and a length of 10 mm into a tube shape, and this is immersed in the urethane resin 10 wt% solution. The solution was impregnated. Next, this was taken out from the solution and put into squeezed water with a roll to remove DMF. Next, this was air-dried, the metal rod in the tube was taken out, and an artificial blood vessel (sample 6) clogged with urethane resin was obtained. This was a rubber-like texture and a sticky feel. This was used as a comparative biological experiment sample.
  • the tubular product (c) used in Example 3 was clogged with gelatin to prepare a tubular product (d) in which leakage of blood was eliminated.
  • the polyamino acid urethane resin solution (A) (concentration 20 wt%) obtained in Example 1 was diluted with dichloroacetic acid to a 5 wt% solution.
  • a metal rod was passed through the tube of the tubular article (d), and this was put into the 5 wt% solution and impregnated with the solution.
  • Comparative Example 4 A tubular product (sample 8) obtained by clogging the tubular product (c) used in Example 4 with gelatin was obtained. This was used as a comparative artificial blood vessel for biological experiments.
  • the polyamino acid urethane resin (A) synthesized in Example 1 (20% by weight DMF solution) was diluted with dichloroacetic acid to give a 3% concentration solution.
  • a polyethylene terephthalate fiber is passed through a tube made by clogging a tubular knitted fabric with an inner diameter of 2 mm and a length of 10 mm with collagen, and this is diluted with dichloroacetic acid and immersed in a polyamino acid urethane solution having a concentration of 3%. Then, the resin solution was impregnated.
  • Fig. 4 shows a tubular product in which an artificial blood vessel made of polyethylene terephthalate (PET) fiber branched into a T-shape is plugged with collagen (e) ⁇ main tube (thick portion): tubular product having an inner diameter of 12 mm and a length of 140 mm, side A metal rod was inserted into a main pipe and a side pipe of a pipe (branch pipe: tubular product having an inner diameter of 8 mm and a length of 150 mm connected to the central portion of the main pipe), and then the polyamino acid urethane resin solution (A) obtained in Example 1 After diluting (concentration 20 wt%) with dichloroacetic acid to a concentration of 3 wt% and immersing the artificial blood vessel into which the metal rod was inserted, it was lifted and desolvated in water, air-dried to extract the metal rod, and coated with PAU An artificial blood vessel (sample 10) of a woven fabric of PET fiber was obtained, which had good tactile sensation and
  • Comparative Example 6 As a comparative example, a tubular product (f) obtained by clogging an artificial blood vessel of a PET fiber fabric branched into a T shape in FIG. 4 with collagen was used as a sample for biological experiment (sample 11).
  • the present invention can be used as an artificial blood vessel.

Abstract

L'objet de la présente invention est de pourvoir à une prothèse vasculaire de petit calibre ayant un diamètre intérieur d'au plus 6 mm quand une prothèse vasculaire à base de fibres PET, de fibres téréphtalate de polybutylène, ou autres fibres polyester aromatiques obtenues par réaction d'un acide dicarboxylique aromatique et d'un diol aliphatique est raccordée à un vaisseau sanguin in situ, qui ne provoque pas de thrombi et ne se bouche pas à long terme. L'objet de la présente invention est également de pourvoir à une prothèse vasculaire très sûre ayant un diamètre intérieur d'au plus 7 mm dans laquelle des fibres PET, qui ont été utilisées par le passé, servent de matériau de base pour empêcher l'épaississement d'une couche de thrombus et une occlusion au niveau d'une ramification, d'une courbure ou d'un site d'anastomose. Pour ce faire, la prothèse vasculaire selon l'invention qui utilise un article tubulaire constitué d'une étoffe tricotée, ou d'une étoffe non tissée à base d'une fibre polyester aromatique comme matériau de base est revêtue ou imprégnée et revêtue d'une résine acide polyamino-uréthanne, qui permet la formation d'un film de cellules endothéliales quand la prothèse vasculaire est raccordée à un vaisseau sanguin in situ et que le sang s'y écoule ; et aucun thrombus ne se formant sur celui-ci, le problème précité peut être résolu.
PCT/JP2012/055151 2011-02-25 2012-02-23 Prothèse vasculaire WO2012115275A1 (fr)

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JP6372049B2 (ja) * 2013-03-25 2018-08-15 株式会社マルイ 人工血管および人工血管の成形方法
KR101587802B1 (ko) * 2013-11-08 2016-02-12 한국과학기술연구원 인공혈관용 구조물 및 이것의 제조방법
CN107213512B (zh) * 2017-06-16 2022-07-08 南京医科大学第一附属医院 一种错时释放双缓释涂层多功能小口径人工血管及其制备方法

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JPS61109569A (ja) * 1984-11-05 1986-05-28 宇部興産株式会社 血管補綴物
JP2005319165A (ja) * 2004-05-11 2005-11-17 Senko Medical Instr Mfg Co Ltd 細胞接着性生体吸収材料

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JPS61109569A (ja) * 1984-11-05 1986-05-28 宇部興産株式会社 血管補綴物
JP2005319165A (ja) * 2004-05-11 2005-11-17 Senko Medical Instr Mfg Co Ltd 細胞接着性生体吸収材料

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MAKOTO KODAMA: "Jinko Kekkan no Ayumi", FUKUOKA IGAKU ZASSHI, vol. 95, no. 9, 2004, pages 210 - 217 *

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