WO2025258253A1 - Vaisseau sanguin artificiel et son procédé de fabrication - Google Patents

Vaisseau sanguin artificiel et son procédé de fabrication

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Publication number
WO2025258253A1
WO2025258253A1 PCT/JP2025/016224 JP2025016224W WO2025258253A1 WO 2025258253 A1 WO2025258253 A1 WO 2025258253A1 JP 2025016224 W JP2025016224 W JP 2025016224W WO 2025258253 A1 WO2025258253 A1 WO 2025258253A1
Authority
WO
WIPO (PCT)
Prior art keywords
polyurethane
artificial blood
blood vessel
porous body
polyurethane porous
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/JP2025/016224
Other languages
English (en)
Japanese (ja)
Inventor
泰史 山村
準二 石川
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toyobo Co Ltd
Original Assignee
Toyobo Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Toyobo Co Ltd filed Critical Toyobo Co Ltd
Publication of WO2025258253A1 publication Critical patent/WO2025258253A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • 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
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges

Definitions

  • the present invention relates to an artificial blood vessel and a method for manufacturing an artificial blood vessel.
  • An artificial intravascular shunt is typically an option when it is difficult to create a natural intravascular shunt.
  • an artificial blood vessel is typically used to connect an artery to a vein (e.g., the cephalic or basilic vein).
  • Patent Document 1 describes how the compliance of an artificial blood vessel made of a porous elastomer can be made to approach that of an artery.
  • Patent Document 2 describes how a vascular graft including a porous polymer graft wall made of cross-linked polyurethane has a Young's modulus of approximately 200 kPa to 850 kPa.
  • the present invention aims to provide an artificial blood vessel that can suppress or reduce turbulence at the anastomosis between the artificial blood vessel and the vein (specifically, the veins of dialysis patients aged 70 ⁇ 10 years, the age group estimated to be most likely to be introduced to dialysis).
  • the present invention also aims to provide a method for manufacturing an artificial blood vessel that makes this possible.
  • the artificial blood vessel of the present invention has the following configuration [1].
  • the present invention includes a tubular porous polyurethane body,
  • the tensile modulus of the polyurethane porous body is 40 kPa or more and 190 kPa or less.
  • the tensile modulus of a tubular polyurethane porous body i.e., a porous polyurethane tube
  • the tensile modulus of a tubular polyurethane porous body is 40 kPa to 190 kPa, thereby suppressing or reducing turbulence at the anastomosis between an artificial blood vessel and a vein (specifically, the veins of dialysis patients aged 70 ⁇ 10 years, the age at which dialysis is most likely to be initiated). This is explained below.
  • the average age at the onset of dialysis is 71.09 years. 1) Based on this, it can be estimated that dialysis is most likely initiated at the age of 70 ⁇ 10 years.
  • the 95% confidence interval for the population mean ⁇ for patients aged 70 ⁇ 10 years can be estimated to be 60 kPa ⁇ 150 kPa. Since artificial blood vessels are sometimes anastomosed to the saphenous vein, the tensile modulus of the saphenous vein in patients aged 70 ⁇ 10 years is likely to fall within the range of 60 kPa to 150 kPa.
  • the tensile modulus of the saphenous vein in individuals aged 62 ⁇ 10 years (80% males) can be estimated to be 115 kPa ⁇ 25 kPa.3
  • the tensile modulus of the veins (specifically, the cephalic, basilic, and saphenous veins) of individuals aged 70 ⁇ 10 years, who are estimated to be at a high risk of receiving dialysis is considered to be highly likely to be between 60 kPa and 150 kPa.
  • the tensile modulus of the porous polyurethane tube is specified to be in the range of 40 kPa to 190 kPa, which largely overlaps with the range of 60 kPa to 150 kPa. Therefore, the rigidity of the porous polyurethane tube is similar to the rigidity of the veins of individuals aged 70 ⁇ 10 years, who are estimated to be at a high risk of receiving dialysis.
  • the inner diameter of the artificial blood vessel of this embodiment can change in response to pulsation without much difference (i.e., change in the same way) with the inner diameter of a vein (specifically, the vein of a dialysis patient aged 70 ⁇ 10 years, the age at which dialysis is most likely to be initiated). Therefore, the artificial blood vessel of this embodiment can suppress or reduce turbulence at the anastomosis between the artificial blood vessel and a vein (specifically, the vein of a dialysis patient aged 70 ⁇ 10 years). As a result, the occurrence of intimal hyperplasia at the anastomosis can be suppressed or reduced, i.e., the intimal thickening at the anastomosis can be suppressed or reduced. Therefore, the occurrence of blockage at the anastomosis between the artificial blood vessel and a vein can be suppressed or reduced.
  • porous nature of the porous polyurethane tube allows tissue, capillaries, cells, etc. to penetrate into the polyurethane porous body. This promotes their infiltration, which in turn promotes intima formation.
  • the artificial blood vessel of the present invention preferably further comprises the following features [2] to [10].
  • [2] The artificial blood vessel according to [1], wherein the tensile modulus is 60 kPa or more and 150 kPa or less.
  • [3] The artificial blood vessel according to [1] or [2], wherein the inner diameter of the polyurethane porous body is 4 mm or more and 6 mm or less.
  • [4] The artificial blood vessel according to any one of [1] to [3], wherein the inner diameter of the polyurethane porous body is 5 mm or more and 6 mm or less.
  • [5] The artificial blood vessel according to any one of [1] to [4], wherein the porous polyurethane body has thermoplastic properties.
  • the polyurethane porous body has at least one peak in a log differential pore volume distribution curve, the peak apex of which is in a pore diameter range of more than 100 ⁇ m and not more than 1,000 ⁇ m; the polyurethane porous body has at least one peak in the log differential pore volume distribution curve, the peak apex of which is in a pore diameter range of 100 ⁇ m or less; [1] - [7] The artificial blood vessel described in any one of [1] to [7]. [9] The artificial blood vessel according to [8], wherein the pore diameter range of more than 100 ⁇ m and not more than 1000 ⁇ m is a pore diameter range of 105 ⁇ m or more and not more than 1000 ⁇ m. [10] The artificial blood vessel according to any one of [1] to [9], which is used for creating a vascular access.
  • the method for producing an artificial blood vessel according to the present invention comprises the following constitution [11].
  • [11] A method for producing an artificial blood vessel according to any one of [1] to [10], A step of preparing a polyurethane porous material stock solution containing a thermoplastic polyurethane elastomer, dimethyl sulfoxide, and a pore-forming agent that is insoluble in the dimethyl sulfoxide and water-soluble; a step of solidifying the polyurethane porous material stock solution by cooling the polyurethane porous material stock solution while the polyurethane porous material stock solution is in a tubular state; and washing the tubular solid product formed by solidifying the polyurethane porous material stock solution with water.
  • a method for manufacturing artificial blood vessels A method for manufacturing artificial blood vessels.
  • the present invention also preferably has the following configuration.
  • the absorbable material comprises gelatin.
  • An artificial blood vessel or a method for producing the same according to any one of the above configurations wherein the thickness of the polyurethane porous body is 0.5 mm or more or 1.0 mm or more.
  • An artificial blood vessel or a method for producing the same according to any one of the above configurations wherein the thickness of the polyurethane porous body is 2.0 mm or less or 1.5 mm or less.
  • An artificial blood vessel or a method for producing the same according to any one of the above configurations, wherein the tensile modulus of elasticity of the polyurethane porous body is 60 kPa or more or 70 kPa or more.
  • the content of the thermoplastic polyurethane elastomer in the polyurethane porous body is 90% by mass or more, or 95% by mass or more; An artificial blood vessel according to any one of the above configurations, or a method for producing the same.
  • the content of the thermoplastic polyurethane elastomer in the polyurethane porous body is 97% by mass or more, or 98% by mass or more; An artificial blood vessel according to any one of the above configurations, or a method for producing the same.
  • the content of the thermoplastic polyurethane elastomer in the polyurethane porous body is 100% by mass; An artificial blood vessel according to any one of the above configurations, or a method for producing the same.
  • the present invention provides an artificial blood vessel that can suppress or reduce turbulence at the anastomosis between the artificial blood vessel and the vein (specifically, the veins of dialysis patients aged 70 ⁇ 10 years, the age group estimated to be most likely to be introduced to dialysis), as well as a method for manufacturing the same.
  • 1 is a photograph of an example of an artificial blood vessel according to the present embodiment taken obliquely from above.
  • 1 is a photograph of an example of an artificial blood vessel according to the present embodiment taken from the front.
  • 1 is a micrograph of a cross section of an example of an artificial blood vessel according to the present embodiment.
  • 1 is a micrograph of a cross section of a polyurethane porous body produced in Example 2.
  • 1 is a micrograph of a cross section of a polyurethane porous body produced in Example 3.
  • 1 is a graph showing the log differential pore volume distribution of the polyurethane porous bodies produced in Examples 2 and 3.
  • 1 is a photograph of the apparatus used to mold a tubular polyurethane porous body in Example 4.
  • the apparatus includes a cylindrical rod and a mold including an inner wall capable of forming a cylindrical cavity concentric with the rod.
  • the mold includes a pair of half-split frames.
  • the photograph shows the apparatus after assembly. 1 is a photograph of the apparatus used to form a tubular polyurethane porous body in Example 4. The photograph shows the apparatus with a pair of frame halves separated.
  • the artificial blood vessel of this embodiment includes a tubular porous polyurethane body, i.e., a porous polyurethane tube.
  • the pores of the porous polyurethane tube have interconnected pores, as described below, and the artificial blood vessel of this embodiment can include an absorbable material that fills the interconnected pores from the inner lumen surface to the outer surface of the porous polyurethane tube.
  • the absorbable material refers to a material that can be decomposed in the body. Examples of absorbable materials include gelatin and collagen. The gelatin may be crosslinked.
  • the artificial blood vessel of this embodiment can be suitably used for creating vascular access.
  • it can be more suitably used for creating vascular access for dialysis.
  • Porous polyurethane pipe> A tubular polyurethane porous body, i.e., a porous polyurethane tube, can be the base of an artificial blood vessel.
  • the porous polyurethane tube has an inner lumen surface (hereinafter sometimes referred to as the "inner surface") and an outer surface.
  • the porous polyurethane tube may be, for example, a straight type, a tapered type, or a short taper type. Of these, the straight type is preferred.
  • the straight type refers to a shape in which the inner diameter is constant throughout the entire porous polyurethane tube. Both ends of the porous polyurethane tube are open.
  • the inner diameter of the porous polyurethane tube is preferably 4 mm or more and 6 mm or less, and more preferably 5 mm or more and 6 mm or less.
  • the artificial blood vessel of this embodiment can be suitably used for creating vascular access.
  • the artificial blood vessel of this embodiment can be even more suitably used for creating vascular access.
  • the porous polyurethane tube is, for example, a tapered type or a short taper type
  • the inner diameter in this specification refers to the maximum inner diameter.
  • the thickness of the porous polyurethane pipe is preferably 0.5 mm or more, and more preferably 1.0 mm or more. On the other hand, the thickness of the porous polyurethane pipe is preferably 2.0 mm or less, and more preferably 1.5 mm or less.
  • the length of the porous polyurethane tube may be, for example, 50 mm or more, 100 mm or more, 200 mm or more, or 300 mm or more.
  • the length of the porous polyurethane tube may be 600 mm or less, or 500 mm or less. Note that the artificial blood vessel may be cut as necessary to adjust its length before placement, and in this paragraph, the length of the porous polyurethane tube refers to the length before cutting.
  • the tensile modulus of the porous polyurethane tube is between 40 kPa and 190 kPa. Therefore, turbulence at the anastomosis between the artificial blood vessel and the vein (specifically, the veins of dialysis patients aged 70 ⁇ 10 years, the age at which dialysis is most likely to be initiated) can be suppressed or reduced. This is explained below.
  • the average age at the onset of dialysis is 71.09 years. 1) Based on this, it can be estimated that dialysis is most likely initiated at the age of 70 ⁇ 10 years.
  • the 95% confidence interval for the population mean ⁇ for patients aged 70 ⁇ 10 years can be estimated to be 60 kPa ⁇ ⁇ ⁇ 150 kPa. Since artificial blood vessels are sometimes anastomosed to the saphenous vein, the tensile modulus of the saphenous vein in patients aged 70 ⁇ 10 years is likely to fall within the range of 60 kPa to 150 kPa.
  • the tensile modulus of the saphenous vein in individuals aged 62 ⁇ 10 years (80% males) can be estimated to be 115 kPa ⁇ 25 kPa.3
  • the tensile modulus of the veins (specifically, the cephalic, basilic, and saphenous veins) of individuals aged 70 ⁇ 10 years, who are estimated to be at a high risk of receiving dialysis is considered to be highly likely to be between 60 kPa and 150 kPa.
  • the tensile modulus of the porous polyurethane tube is specified to be in the range of 40 kPa to 190 kPa, which largely overlaps with the range of 60 kPa to 150 kPa. Therefore, the rigidity of the porous polyurethane tube is similar to the rigidity of the veins of individuals aged 70 ⁇ 10 years, who are estimated to be at a high risk of receiving dialysis.
  • the inner diameter of the artificial blood vessel of this embodiment can change in response to pulsation without much difference (i.e., can change in the same way) with the inner diameter of a vein (specifically, the vein of a dialysis patient aged 70 ⁇ 10 years, the age at which dialysis is most likely to be initiated). Therefore, the artificial blood vessel of this embodiment can suppress or reduce turbulence at the anastomosis between the artificial blood vessel and a vein (specifically, the vein of a dialysis patient aged 70 ⁇ 10 years).
  • the occurrence of intimal hyperplasia at the anastomosis can be suppressed or reduced, i.e., the intimal thickening at the anastomosis can be suppressed or reduced. Therefore, the occurrence of blockage at the anastomosis between the artificial blood vessel and a vein can be suppressed or reduced.
  • the tensile modulus of the porous polyurethane tube is preferably between 60 kPa and 150 kPa.
  • a modulus of 60 kPa or more and 150 kPa or less can further suppress or reduce turbulence at the anastomosis between the artificial blood vessel and the vein (specifically, the vein of a dialysis patient aged 70 ⁇ 10 years, the age group estimated to be most likely to be introduced to dialysis).
  • the tensile modulus of elasticity of the porous polyurethane pipe is preferably 70 kPa or more, and more preferably 80 kPa or more.
  • the tensile modulus of elasticity of the porous polyurethane pipe is preferably 140 kPa or less, and more preferably 130 kPa or less.
  • the tensile modulus is a value measured using the method described in the examples.
  • Porous polyurethane tubes are porous. Specifically, they have interconnected pores from the inner surface to the outer surface. This allows tissues, capillaries, cells, etc. to penetrate into the polyurethane porous body. This promotes their infiltration, which in turn promotes intima formation.
  • the porosity, or air porosity, of a porous polyurethane pipe is preferably 88.0% or higher. This is because the higher the porosity, the lower the tensile modulus and the easier it is for tissues, capillaries, cells, etc. to penetrate into the polyurethane porous body.
  • the porosity may be, for example, 90.0% or higher, or 92.0% or higher.
  • the porosity of a porous polyurethane pipe is preferably 95.0% or lower, and more preferably 94.0% or lower. This is because if the porosity is excessively high, the tensile modulus may become excessively low.
  • the porosity is a value measured using the method described in the examples.
  • the porous polyurethane tube has at least one peak (hereinafter sometimes referred to as the "L peak”) in the pore diameter range of more than 100 ⁇ m and not more than 1000 ⁇ m in its log differential pore volume distribution curve, and at least one peak (hereinafter sometimes referred to as the "S peak”) in the pore diameter range of not more than 100 ⁇ m.
  • L peak peak in the pore diameter range of more than 100 ⁇ m and not more than 1000 ⁇ m in its log differential pore volume distribution curve
  • S peak peak
  • the porous polyurethane tube has an L peak, that is, has relatively large pores, tissues, capillaries, cells, etc. can more easily penetrate the polyurethane porous body.
  • the porous polyurethane tube has an S peak, that is, has very small pores, when tissues, capillaries, cells, etc. enter the very small pores, it is possible to increase the frequency of contact with the artificial blood vessel, thereby promoting tissue settlement.
  • the L peak may have a peak apex in the pore diameter range of 105 ⁇ m or more and 1000 ⁇ m or less, or may have a peak apex in the pore diameter range of 120 ⁇ m or more and 1000 ⁇ m or less.
  • the log differential pore volume of the L peak is preferably 3.0 mL/g or more, and more preferably 4.0 mL/g or more.
  • the log differential pore volume of the L peak may be, for example, 8.0 mL/g or less, or 7.0 mL/g or less.
  • the S peak may have a peak apex in the pore diameter range of 60 ⁇ m or less, or may have a peak apex in the pore diameter range of 40 ⁇ m or less.
  • the log differential pore volume of the S peak is preferably 1.0 mL/g or more.
  • the log differential pore volume of the S peak may be, for example, 6.0 mL/g or less, or even 5.0 mL/g or less.
  • the porous polyurethane pipe has thermoplastic properties. If the porous polyurethane pipe has thermoplastic properties, it is easy to manufacture the porous polyurethane pipe.
  • the polyurethane porous body contains a thermoplastic polyurethane elastomer.
  • the porous polyurethane tube can be easily manufactured. Furthermore, in this case, it is possible to impart entropy elasticity to the polyurethane porous body, thereby providing an artificial blood vessel that is easy to place.
  • the porous polyurethane tube may further contain components other than the thermoplastic polyurethane elastomer (for example, additives, elastomers other than the thermoplastic polyurethane elastomer).
  • thermoplastic polyurethane elastomers examples include Pellethane (registered trademark), ChronoFlex (registered trademark), ChronoThane (registered trademark), and HydroThane (registered trademark). These are preferred because medical grade products are commercially available.
  • Thermoplastic polyurethane elastomer preferably has entropy elasticity at least between 30°C and 42°C.
  • the entropy elasticity of the porous polyurethane tube makes it possible to provide an artificial blood vessel that is easy to place.
  • thermoplastic polyurethane elastomer content in the porous polyurethane pipe is preferably 90% by mass or more, more preferably 95% by mass or more, even more preferably 97% by mass or more, and even more preferably 98% by mass or more.
  • the thermoplastic polyurethane elastomer content in the porous polyurethane pipe may be 100% by mass.
  • the method for producing an artificial blood vessel in this embodiment includes the steps of preparing a porous polyurethane stock solution containing a thermoplastic polyurethane elastomer, dimethyl sulfoxide, and a pore-forming agent that is insoluble in dimethyl sulfoxide and water-soluble (hereinafter referred to as the "preparation step”); solidifying the porous polyurethane stock solution by cooling it while it is in a tubular state (hereinafter referred to as the "solidification step”); and washing the tubular solid formed by solidifying the porous polyurethane stock solution with water (hereinafter referred to as the "washing step”).
  • the method for producing an artificial blood vessel in this embodiment can produce an artificial blood vessel containing a porous polyurethane material in which pores derived from the pore-forming agent and pores derived from dimethyl sulfoxide crystals are formed.
  • the method for producing an artificial blood vessel in this embodiment may further include the step of drying the porous polyurethane tube obtained in the washing step.
  • a stock solution of porous polyurethane is prepared.
  • the stock solution of porous polyurethane can be prepared by mixing and stirring a thermoplastic polyurethane elastomer and dimethyl sulfoxide, and then adding a pore-forming agent and stirring the mixture, or by mixing a thermoplastic polyurethane elastomer and a pore-forming agent with dimethyl sulfoxide and stirring the mixture.
  • the former is preferred.
  • the temperature of the dimethyl sulfoxide mixed with at least the thermoplastic polyurethane elastomer is 70°C or higher. If the temperature is 70°C or higher, the thermoplastic polyurethane elastomer can be easily dissolved in the dimethyl sulfoxide.
  • the temperature of the dimethyl sulfoxide may be, for example, 80°C or higher, or 90°C or higher.
  • the temperature of the dimethyl sulfoxide may be, for example, 150°C or lower, or 120°C or lower.
  • Porosity-forming agents are particles that are insoluble in dimethyl sulfoxide but water-soluble.
  • the particle size of the pore-forming agent can be adjusted using a mortar or sieve.
  • An example of a pore-forming agent is sodium chloride.
  • thermoplastic polyurethane elastomer is preferably 3% by mass or more, more preferably 4% by mass or more, and even more preferably 5% by mass or more, based on 100% by mass of the polyurethane porous liquid concentrate.
  • the content of thermoplastic polyurethane elastomer is preferably 7% by mass or less, more preferably 6% by mass or less, and even more preferably 5.5% by mass or less, based on 100% by mass of the polyurethane porous liquid concentrate.
  • the lower the content of thermoplastic polyurethane elastomer the more likely it is that the porosity of the porous polyurethane pipe will increase, and therefore the lower the tensile modulus of elasticity will be.
  • the pore-forming agent content is preferably 10% by mass or more, more preferably 20% by mass or more, and even more preferably 30% by mass or more, based on 100% by mass of the polyurethane porous material stock solution.
  • the pore-forming agent content is preferably 60% by mass or less, more preferably 55% by mass or less, and even more preferably 50% by mass or less, based on 100% by mass of the polyurethane porous material stock solution.
  • the total content of the thermoplastic polyurethane elastomer, dimethyl sulfoxide, and pore-forming agent is preferably 90% by mass or more, more preferably 95% by mass or more, even more preferably 98% by mass or more, and even more preferably 100% by mass, based on 100% by mass of the polyurethane porous material solution.
  • the porous polyurethane liquid is solidified by cooling it while it is in a tubular state.
  • a cylindrical rod and a mold including an inner wall capable of forming a cylindrical cavity concentric with the rod, and fill the space between the rod and the inner wall (i.e., the tubular space) with the porous polyurethane liquid.
  • the porous polyurethane stock solution is cooled to below the freezing point of dimethyl sulfoxide.
  • the porous polyurethane stock solution can be cooled to, for example, below 10°C, below 0°C, or below -10°C.
  • ⁇ 2.3. Cleaning step> the tubular solid formed by solidifying the polyurethane porous material stock solution is washed with water. Because both dimethyl sulfoxide and the pore-forming agent are soluble in water, washing the tubular solid with water can remove the dimethyl sulfoxide and pore-forming agent from the tubular solid. Therefore, a porous polyurethane tube can be obtained by washing the tubular solid with water. For example, tap water, ion-exchanged water, distilled water, or ultrapure water can be used to wash the tubular solid. Note that water washing may be performed multiple times.
  • the tubular solid may be washed with water below the freezing point of dimethyl sulfoxide (e.g., ice-cold water), and then further washed with warm water at 50°C to 70°C. After washing with water, the porous polyurethane tube may be dried.
  • dimethyl sulfoxide e.g., ice-cold water
  • the pores of the porous polyurethane tube may be filled with an absorbent material, and the porous polyurethane tube may be cut to adjust its length.
  • an artificial blood vessel is used to create vascular access.
  • this embodiment is not limited to this configuration.
  • an artificial blood vessel may also be used for revascularization.
  • the artificial blood vessel is described as including an absorbent material that fills the connecting pores from the inner lumen surface to the outer surface of the porous polyurethane tube.
  • this embodiment is not limited to this configuration.
  • the artificial blood vessel may be configured not to include an absorbent material that fills the connecting pores from the inner lumen surface to the outer surface of the porous polyurethane tube, but to include an inner membrane that covers the inner lumen surface of the porous polyurethane tube.
  • the artificial blood vessel may be configured not to include an absorbent material that fills the connecting pores from the inner lumen surface to the outer surface of the porous polyurethane tube, but to include an outer membrane that covers the outer surface of the porous polyurethane tube.
  • These membranes may be formed from an absorbent material. In other words, these membranes may contain an absorbent material.
  • an artificial blood vessel is manufactured using a method including a preparation step (i.e., a step of preparing a porous polyurethane stock solution containing a thermoplastic polyurethane elastomer, dimethyl sulfoxide, and a pore-forming agent), a solidification step (i.e., a step of solidifying the porous polyurethane stock solution by cooling it while it is in a tubular state), and a washing step (i.e., a step of washing the tubular solid with water).
  • a preparation step i.e., a step of preparing a porous polyurethane stock solution containing a thermoplastic polyurethane elastomer, dimethyl sulfoxide, and a pore-forming agent
  • a solidification step i.e., a step of solidifying the porous polyurethane stock solution by cooling it while it is in a tubular state
  • a washing step i.e., a step of washing the tubular solid with
  • the porosity was calculated using the following formula.
  • Porosity (%) ⁇ 1-(W p /W np ) ⁇ 100
  • W p ie, the mass of the film sample
  • W np is calculated by the following equation.
  • W np (5 x 5 x T) x 1.05
  • a value in cm is substituted for T, that is, the thickness of the film sample.
  • the pore size distribution was measured by mercury intrusion porosimetry at the request of Shimadzu Techno Research Corporation.
  • the measurement device used was a pore size distribution measuring device, Autopore V9620, manufactured by Micromeritics.
  • the pore size distribution was measured at an initial pressure of 1.5 kPa.
  • Example 1 Commercially available sodium chloride (NaCl) was pulverized in an agate mortar. From the pulverized material, the component that passed through a stainless steel sieve with 106 ⁇ m openings but did not pass through a 45 ⁇ m opening sieve was collected as a pore-forming agent. 10 parts by mass of polyurethane (Lubrizol, Pellethane 2363-80AE) and 90 parts by mass of dimethyl sulfoxide (DMSO) were mixed and dissolved at 90° C. This gave a 10% by mass polyurethane solution.
  • NaCl sodium chloride
  • the PU porous material stock solution was poured into a 2 mm high silicone rubber mold placed on a 1 mm thick first silicone rubber sheet. Next, a 1 mm thick second silicone rubber sheet was placed on the mold. This sandwiched the mold between a pair of silicone rubber sheets. These were then sandwiched between a pair of glass plates and cooled overnight in a -20°C freezer to solidify the polyurethane porous material stock solution in the mold. The flat coagulated material was removed from the mold and immersed in ice-cold water.
  • Example 2 A flat membrane of a polyurethane porous material was produced in the same manner as in Example 1, except that the amount of the pore-forming agent added was changed to 0.5 parts by mass. A micrograph of the cross section of the polyurethane porous body is shown in Figure 2. The porosity of the polyurethane porous body was 88.3%, and the tensile modulus was 182 kPa.
  • Example 3 A flat membrane of a polyurethane porous material was prepared in the same manner as in Example 1, except that a sieve with a mesh size of 212 ⁇ m was used instead of the sieve with a mesh size of 106 ⁇ m, and a sieve with a mesh size of 106 ⁇ m was used instead of the sieve with a mesh size of 45 ⁇ m. That is, a flat membrane of a polyurethane porous material was prepared in the same manner as in Example 1, except that a component of the pulverized sodium chloride that passed through a sieve with a mesh size of 212 ⁇ m but not a sieve with a mesh size of 106 ⁇ m was used as a pore-forming agent. A micrograph of the cross section of the polyurethane porous body is shown in Figure 3. The porosity of the polyurethane porous body was 92.4% and the tensile modulus was 112 kPa.
  • Comparative Example 1 A flat membrane of a polyurethane porous body was prepared in the same manner as in Example 1, except that a 15% by mass polyurethane solution was used instead of the 10% by mass polyurethane solution.
  • the 15% by mass polyurethane solution was prepared by mixing and dissolving 15 parts by mass of polyurethane (Pellethane 2363-80AE, manufactured by Lubrizol) and 85 parts by mass of dimethyl sulfoxide (DMSO) at 90°C.
  • the porosity of the polyurethane porous body was 87.9%, and the tensile modulus was 233 kPa.
  • Comparative Example 2 A flat membrane of a polyurethane porous material was produced in the same manner as in Example 1, except that no pore-forming agent was used (that is, no pore-forming agent was added to the 10% by mass polyurethane solution). The porosity of the polyurethane porous body was 84.8%, and the tensile modulus was 665 kPa.
  • Comparative Example 3 A flat membrane of a polyurethane porous body was prepared in the same manner as in Example 1, except that a 15% by mass polyurethane solution was used instead of the 10% by mass polyurethane solution, and no pore-forming agent was used (i.e., no pore-forming agent was added to the 15% by mass polyurethane solution).
  • the porosity of the polyurethane porous body was 78.0%, and the tensile modulus was 2064 kPa.
  • the "mass ratio of the pore-forming agent” refers to the amount (mass) of the pore-forming agent added relative to 1 part by mass of the polyurethane solution.
  • the polyurethane porous bodies produced in Examples 1 to 3 exhibited a tensile modulus equivalent to that of the veins of people aged 70 ⁇ 10 years, the age group most likely to be introduced to dialysis (specifically, the cephalic, basilic, and saphenous veins).
  • pore size distribution measurements were performed in Examples 2 and 3.
  • a peak near a pore size of 10 ⁇ m and a series of peaks with pore sizes of 100 ⁇ m or more were observed.
  • a peak near a pore size of 10 ⁇ m and a series of peaks with pore sizes of 100 ⁇ m or more were also observed.
  • the former i.e., the peak near a pore size of 10 ⁇ m
  • the latter i.e., the series of peaks with pore sizes of 100 ⁇ m or more
  • the pore diameter of the series of peaks presumed to be derived from pores generated by the pore-forming agent increases with increasing pore-forming agent (see Figure 4).
  • the pore diameter of the peaks presumed to be derived from pores generated by DMSO crystals i.e., peaks with pore diameters around 10 ⁇ m
  • this pore diameter can be controlled by the cooling rate when solidifying the polyurethane porous material stock solution, the concentration of the polyurethane porous material, etc.
  • Example 4 As shown in Figures 5A and 5B, a cylindrical rod and a mold including an inner wall capable of forming a cylindrical cavity concentric with the rod were prepared, and a tubular polyurethane porous body was molded. Specifically, the space between the rod and the inner wall (i.e., the tubular space) was filled with the polyurethane porous body concentrate prepared in Example 1. This was cooled overnight in a -20°C freezer. After cooling, the rod and mold were removed to obtain a tubular coagulated body, which was immersed in ice-cold water and then washed with warm water at 60°C. This was then dried under reduced pressure. A tubular polyurethane porous body was thus obtained.

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Abstract

Le but de la présente invention est de fournir un vaisseau sanguin artificiel qui peut supprimer ou réduire les turbulences dans une anastomose entre le vaisseau sanguin artificiel et une veine. Un autre but est de fournir un procédé de production du vaisseau sanguin artificiel qui peut atteindre l'objectif susmentionné. Le module d'élasticité en traction d'un corps poreux en polyuréthane du vaisseau sanguin artificiel est compris entre 40 et 190 kPa. Le procédé de production du vaisseau sanguin artificiel comprend : une étape de préparation d'une solution mère de corps poreux de polyuréthane contenant un élastomère de polyuréthane thermoplastique, du diméthylsulfoxyde et un agent porogène hydrosoluble qui est insoluble dans le diméthylsulfoxyde ; une étape de solidification de la solution mère de corps poreux de polyuréthane par refroidissement de celle-ci dans un état où elle forme une structure tubulaire ; et une étape de lavage à l'eau du matériau solide tubulaire obtenu par solidification de la solution mère de corps poreux de polyuréthane.
PCT/JP2025/016224 2024-06-12 2025-04-28 Vaisseau sanguin artificiel et son procédé de fabrication Pending WO2025258253A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59181149A (ja) * 1978-02-14 1984-10-15 ベー・ブラウン―エス・エス・ツエー・アクチエンゲゼルシヤフト 人工血管の製造方法
JPS60182959A (ja) * 1984-03-01 1985-09-18 鐘淵化学工業株式会社 人工血管
JPS61185271A (ja) * 1985-02-09 1986-08-18 鐘淵化学工業株式会社 コンプライアンスおよび応力−歪曲線が生体血管に近似している人工血管およびその製造方法
JPH0321255A (ja) * 1989-06-19 1991-01-30 Kanebo Ltd 人工血管及びその製造方法
JP2004097687A (ja) * 2002-09-12 2004-04-02 Bridgestone Corp 生体用樹脂基材及びその製造方法
JP2006141681A (ja) * 2004-11-19 2006-06-08 National Cardiovascular Center 人工血管
US20200261207A1 (en) * 2017-01-24 2020-08-20 University Of Washington Pro-healing elastic angiogenic microporous vascular graft

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59181149A (ja) * 1978-02-14 1984-10-15 ベー・ブラウン―エス・エス・ツエー・アクチエンゲゼルシヤフト 人工血管の製造方法
JPS60182959A (ja) * 1984-03-01 1985-09-18 鐘淵化学工業株式会社 人工血管
JPS61185271A (ja) * 1985-02-09 1986-08-18 鐘淵化学工業株式会社 コンプライアンスおよび応力−歪曲線が生体血管に近似している人工血管およびその製造方法
JPH0321255A (ja) * 1989-06-19 1991-01-30 Kanebo Ltd 人工血管及びその製造方法
JP2004097687A (ja) * 2002-09-12 2004-04-02 Bridgestone Corp 生体用樹脂基材及びその製造方法
JP2006141681A (ja) * 2004-11-19 2006-06-08 National Cardiovascular Center 人工血管
US20200261207A1 (en) * 2017-01-24 2020-08-20 University Of Washington Pro-healing elastic angiogenic microporous vascular graft

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