WO2022209633A1 - 人工血管 - Google Patents

人工血管 Download PDF

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Publication number
WO2022209633A1
WO2022209633A1 PCT/JP2022/010044 JP2022010044W WO2022209633A1 WO 2022209633 A1 WO2022209633 A1 WO 2022209633A1 JP 2022010044 W JP2022010044 W JP 2022010044W WO 2022209633 A1 WO2022209633 A1 WO 2022209633A1
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WO
WIPO (PCT)
Prior art keywords
layer
blood vessel
artificial blood
inner layer
microfibers
Prior art date
Application number
PCT/JP2022/010044
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English (en)
French (fr)
Japanese (ja)
Inventor
公正 数野
遼平 小林
Original Assignee
テルモ株式会社
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.)
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Publication date
Application filed by テルモ株式会社 filed Critical テルモ株式会社
Priority to JP2023510755A priority Critical patent/JPWO2022209633A1/ja
Publication of WO2022209633A1 publication Critical patent/WO2022209633A1/ja

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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
    • A61L27/14—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
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials

Definitions

  • the present invention relates to artificial blood vessels.
  • the artificial blood vessel used in such cases should not only be able to transport blood, but should also undergo endothelialization, in which the inside of the artificial blood vessel is covered with endothelial cells after surgery.
  • an artificial blood vessel using a woven fabric woven with a thick elastic yarn having a single filament fineness of 1.0 dtex or more for the warp and a yarn thinner than the warp for the weft has been proposed (for example, Patent Document 1).
  • Patent Document 1 an inner layer tubular fabric using a thick elastic yarn with a single yarn fineness of 1.0 dtex or more for the warp and an outer layer tubular fabric using a thick yarn for the weft It adopts a multiple tubular woven structure in which the woven fabric is layered in a double weave. For this reason, the amount of thin threads exposed on the inner surface of the artificial blood vessel is limited, and the inner side of the artificial blood vessel cannot be endothelialized sufficiently.
  • an object of the present invention is to provide an artificial blood vessel whose inner side is efficiently endothelialized while maintaining strength as an artificial blood vessel.
  • the present invention has a cylindrical inner layer that is a fabric mainly made of microfibers having a single yarn diameter of 7 ⁇ m or less, and a cylindrical reinforcing layer that is applied or bonded to the outer surface of the inner layer, and the micro A vascular prosthesis in which the fibers are exposed over the entire inner surface of the inner layer.
  • an artificial blood vessel whose inner side is efficiently endothelialized while maintaining strength as an artificial blood vessel.
  • FIG. 4 is a schematic diagram showing positions through which stainless steel wires are passed when measuring the suture holding strength of an artificial blood vessel. It is a figure which shows the division
  • the present invention has a cylindrical inner layer that is a fabric mainly made of microfibers having a single yarn diameter of 7 ⁇ m or less, and a cylindrical reinforcing layer that is applied or bonded to the outer surface of the inner layer, and the micro A vascular prosthesis in which the fibers are exposed over the entire inner surface of the inner layer.
  • microfibers having a single yarn diameter of 7 ⁇ m or less are used as the main material for the inner layer, and the microfibers are exposed over the entire inner surface of the inner layer. Adhesion with vascular endothelial cells is improved, and adhesion of endothelial cells is improved.
  • strength as an artificial blood vessel can be improved by using a reinforcing layer on the outside.
  • the artificial blood vessel according to one embodiment of the present invention will be described in detail below.
  • FIG. 1 is a diagram showing an artificial blood vessel 1 according to this embodiment.
  • FIG. 1(A) is a perspective view of the artificial blood vessel 1
  • FIG. 1(B) is a cross-sectional view of the artificial blood vessel 1 taken along line AA in FIG. 1(A).
  • the artificial blood vessel 1 has a bellows shape that is continuous in the longitudinal direction.
  • One of the bellows of the artificial blood vessel 1 is called crimp CR.
  • Line AA in FIG. 1A is a line passing through the trough portion of the bellows.
  • the artificial blood vessel 1 has a tubular inner layer 11 and a tubular reinforcing layer 14 arranged on the outer surface of the inner layer 11 .
  • reinforcing layer 14 has impermeable layer 12 and outer layer 13 .
  • the vascular prosthesis 1 has a three-layer structure of an inner layer 11 , an impervious layer 12 and an outer layer 13 .
  • the artificial blood vessel 1 is a hollow tubular structure with an inner diameter of ⁇ 1.
  • the inner layer 11 is a fabric containing microfibers having a single yarn diameter of 7 ⁇ m or less as a main material, and has a tubular shape.
  • the material of the microfiber is not particularly limited, but examples thereof include flexible synthetic resin fibers such as polyester.
  • polyester for example, polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and the like can be preferably used.
  • Fabrics include woven fabrics, knitted fabrics, non-woven fabrics, etc., and any of them can be used, but knitted fabrics are suitable for the inner layer 11 of the artificial blood vessel 1 of the present invention.
  • the inner layer 11 By making the inner layer 11 a knitted fabric, it is not necessary to use thick yarns for the warp as in the case of a woven fabric, so that the ratio of microfibers exposed to the inner surface of the artificial blood vessel can be increased, and the efficiency of endothelialization can be improved. .
  • the inner layer 11 contains microfibers having a single yarn diameter of 7 ⁇ m or less as a main material. Above all, it is preferable that the single yarn diameter of the microfiber is 3 ⁇ m or more. That is, the inner layer 11 is preferably formed mainly of microfibers having a single yarn diameter of 3 ⁇ m or more and 7 ⁇ m or less.
  • microfibers refer to fibers having a single filament fineness of less than 1.0 dtex.
  • the single fiber diameter of the microfiber is obtained by observing the substrate cut open on the plane with an SEM and measuring the outer diameter of different fibers at a certain number (20 points) with a CCD measurement tool. Use the average of the values.
  • the single thread diameter of the microfiber as the main material of the inner layer 11 is thicker than 7 ⁇ m, the efficiency of endothelialization in which the inner side of the artificial blood vessel is covered with endothelial cells deteriorates. Further, it is preferable that the single thread diameter of the microfiber as the main material of the inner layer 11 is 3 ⁇ m or more because the strength as the artificial blood vessel, particularly the suture holding strength, is excellent.
  • the inner layer 11 contains more than 50% by mass, more preferably 70% by mass or more, still more preferably 90% by mass or more, and even more preferably 95% by mass of microfibers having the above-described predetermined single yarn diameter. More than 99% by mass or more is particularly preferable.
  • the inner layer 11 is made of microfibers having the above-described prescribed single yarn diameter (the proportion of microfibers having the prescribed single yarn diameter is 100% by mass).
  • microfiber is not particularly limited, it is preferable to use it in the form of multifilament from the viewpoint of strength, uniformity of physical properties, and flexibility.
  • the microfibers may or may not be crimped.
  • the fineness of the microfibers is not particularly limited, it is preferably 5 to 200 dtex. If it is 5 dtex or more, it is superior in strength. Moreover, if it is 200 dtex or less, it is preferable because it is excellent in flexibility.
  • the single filament fineness of the microfibers should be less than 1.0 dtex, preferably 0.5 dtex or less. Within the above range, the adhesion of endothelial cells can be further improved.
  • the fineness is a regular fineness measured at a predetermined weight of 0.045 cN/dtex according to JIS L 1013 (2010) 8.3.1 A method. Further, the single yarn fineness can be calculated by dividing this by the number of single yarns.
  • the water permeability of the inner layer 11 is not particularly limited, but is, for example, 3000-7500 ml/min/cm 2 , preferably 6800-7100 ml/min/cm 2 .
  • the water permeability is measured as follows. That is, one end of the tubular inner layer 11 is closed, water filtered by a reverse osmosis membrane is injected from the other end for a predetermined time so that a water pressure of 16 kPa is applied to the inner wall, and the water leaking from the tube wall per unit area of the tube wall Calculate and obtain the amount per hour.
  • the permeability of other layers such as the impermeable layer and the outer layer can also be measured by the same method.
  • the thickness of the inner layer is not particularly limited and can be adjusted as appropriate.
  • the microfibers having the predetermined single thread diameter are exposed over the entire inner surface of the inner layer.
  • the phrase “exposed over the entirety” means that the tubular structure is exposed from one end through the center to the other end regardless of the position in the structure.
  • a specific form is a form in which the surface of the fabric containing the microfiber as a main material is exposed over the entire inner surface of the inner layer.
  • a biodegradable coating such as gelatin may be applied to the inner surface of the inner layer.
  • the biodegradable coating decomposes after being implanted into the living body, and the microfibers having the predetermined single thread diameter are exposed over the entire inner surface of the inner layer. included.
  • the inner layer 11 is formed only of microfibers having the above-mentioned predetermined single thread diameter.
  • the inner layer 11 is formed only of microfibers having the above-mentioned predetermined single thread diameter.
  • the artificial blood vessel 1 of the present invention has a reinforcing layer 14 applied or attached to the outer surface of the inner layer 11 .
  • a water-impervious layer 12 formed of a resin having water-impervious properties and elasticity
  • an outer layer 13 containing a layer of fabric whose main material is fibers having a single yarn diameter of 10 ⁇ m or more and 55 ⁇ m or less, or both of them. preferably included.
  • the waterproof layer flexibility can be imparted to the artificial blood vessel, and intrusion of cells and body fluids can be prevented.
  • strength can be ensured by providing the outer layer.
  • a metal mesh structure such as a general stent graft is not included in the reinforcing layer in the present invention.
  • the impermeable layer 12 is preferably made of resin having impermeability and elasticity.
  • elastic resins include, but are not limited to, styrene-based elastomers and mixtures thereof. Gelatin or collagen can also be used.
  • Styrene-based elastomers are not particularly limited, but those mainly composed of a copolymer composed of a portion composed mainly of styrene and a portion composed of butadiene and/or isoprene and/or hydrogenated products thereof. mentioned.
  • the impermeable layer can be produced, for example, by molding a material obtained by mixing an appropriate amount of scraone, which is a plasticizer, into a styrene-based elastomer into a sheet using a conventional method, such as a heat press.
  • the impermeable layer thus obtained can be adhered to the outer surface of the inner layer, for example, by heat-sealing.
  • a waterproof layer can be formed by applying these gels to the outer surface of the inner layer.
  • the impermeable layer 12 is formed to have impermeability.
  • having water impermeability means that the above-mentioned water permeability is 1.0 ml/min/cm 2 or less.
  • the thickness of the impermeable layer is not particularly limited and can be adjusted as appropriate.
  • the outer layer 13 preferably has a layer of fabric whose main material is fibers having a single yarn diameter of 10 ⁇ m or more and 55 ⁇ m or less.
  • a fabric containing flexible synthetic resin fibers such as polyester can be used.
  • Fabrics include woven fabrics, knitted fabrics, non-woven fabrics, etc., but knitted fabrics are suitable for the outer layer 13 of the artificial blood vessel 1 .
  • the outer layer 13 is not particularly limited, it preferably has a fabric layer mainly composed of fibers having a single yarn diameter of 10 ⁇ m or more and 55 ⁇ m or less. Among them, a layer composed of a knitted fabric mainly composed of fiber having a single yarn diameter of 13 ⁇ m is preferable as the layer.
  • the single fiber diameter of the fiber is 55 ⁇ m or less, the flexibility as an artificial blood vessel can be improved. Further, when the thickness is 10 ⁇ m or more, the strength as an artificial blood vessel can be improved.
  • the fibers may or may not be crimped.
  • the outer layer 13 further has a coating layer on the outside of the fabric layer mainly composed of fibers having a single yarn diameter of 10 ⁇ m or more and 55 ⁇ m or less for the purpose of improving water impermeability, strength, biocompatibility, etc. You may have A specific form of the coating layer is not particularly limited. In addition, when it has a coating layer, it is considered as an outer layer including the portion of the coating layer.
  • the water permeability of the outer layer is not particularly limited and can be adjusted as appropriate.
  • the thickness of the outer layer is not particularly limited and can be adjusted as appropriate.
  • the inner diameter of the inner layer which is the inner diameter of the artificial blood vessel, is preferably 5 mm or more, more preferably 8 mm or more. Within the above range, the effects of the present invention can be obtained more remarkably.
  • the artificial blood vessel of the present invention has excellent strength and excellent affinity with vascular endothelial cells. Therefore, in addition to being suitably used for reconstructing, repairing, or replacing a damaged blood vessel, it can be used to improve stenosis by inserting it into a stenotic site of a blood vessel, like a stent.
  • Example 1 and 2 and Comparative Examples 1 and 2 artificial blood vessels shown in Table 1 below were prepared, and the suture holding strength, which is one index of strength as an artificial blood vessel, was confirmed.
  • the artificial blood vessel had a cylindrical structure with an inner diameter of 8 mm and a length of about 5 cm.
  • Comparative Example 1 has only an inner layer
  • Example 1 has a waterproof layer as a reinforcing layer on the outer surface of the inner layer
  • Example 2 and Comparative Example 2 have a waterproof layer and an outer layer as reinforcing layers on the outer surface of the inner layer. have in order.
  • knitted fabric was used for the inner layer and the outer layer, and a material obtained by mixing an appropriate amount of squalane, which is a plasticizer, with a styrene-based elastomer was used for the impermeable layer.
  • the inner layer and the outer layer are knitted fabrics using a single fiber, and the material, single yarn diameter, fineness, single yarn fineness, and crimp in Table 1 are, respectively, It is the value for the single fiber in question.
  • Examples 3 to 6 and Comparative Example 3 artificial blood vessels shown in Table 2 below were prepared, and the progress of endothelialization of the inner wall of the artificial blood vessel was confirmed.
  • the artificial blood vessel had a cylindrical structure with an inner diameter of 8 mm and a length of about 5 cm.
  • the vascular prostheses of each of the examples and comparative examples have, in this order, a waterproof layer and an outer layer as reinforcing layers on the outer surface of the inner layer.
  • knitted fabric was used for the inner layer and the outer layer, and a material obtained by mixing an appropriate amount of squalane, which is a plasticizer, with a styrene-based elastomer was used for the impermeable layer.
  • the inner layer and the outer layer are knitted fabrics using a single fiber, and the material, single yarn diameter, fineness, single yarn fineness, and crimp in Table 2 are, respectively, It is the value for the single fiber in question.
  • FIG. 3 is a diagram showing a method of dividing the extracted artificial blood vessel. As shown in FIG. 3, a predetermined length was cut out, firstly divided into two lengthwise, and further divided into two lengthwise pieces to prepare small pieces A to D. FIG. 3
  • the degree of endothelialization was observed by observing the inner walls of these small pieces with the naked eye and by observing stained sections.
  • the inner layer 11 by making the inner layer 11 a knitted fabric, it is not necessary to use thick yarns for the warp as in the case of a woven fabric. Therefore, it is possible to increase the ratio of microfibers exposed to the inner surface of the artificial blood vessel and improve the efficiency of endothelialization. can be done.
  • the microfibers are exposed on the entire inner surface of the artificial blood vessel, and the efficiency of endothelialization can be further increased.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Vascular Medicine (AREA)
  • Prostheses (AREA)
PCT/JP2022/010044 2021-03-30 2022-03-08 人工血管 WO2022209633A1 (ja)

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JP2023510755A JPWO2022209633A1 (ru) 2021-03-30 2022-03-08

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JP2021057590 2021-03-30

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6077764A (ja) * 1983-10-05 1985-05-02 東レ株式会社 人工血管
JP2005124959A (ja) * 2003-10-27 2005-05-19 Yasuharu Noisshiki 低血液透過性医用材料
JP2005261867A (ja) * 2004-02-18 2005-09-29 Ube Ind Ltd 管状の人工器官
WO2015080143A1 (ja) * 2013-11-29 2015-06-04 東レ株式会社 人工血管
WO2015122429A1 (ja) * 2014-02-12 2015-08-20 東レ株式会社 人工血管
JP2017506921A (ja) * 2014-02-21 2017-03-16 ヒーリオニクス・コーポレイションＨｅａｌｉｏｎｉｃｓ Ｃｏｒｐｏｒａｔｉｏｎ 血管移植片およびその開存性を維持する方法
WO2019208262A1 (ja) * 2018-04-26 2019-10-31 東レ株式会社 筒状織物およびこれを用いた医療用基材

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6077764A (ja) * 1983-10-05 1985-05-02 東レ株式会社 人工血管
JP2005124959A (ja) * 2003-10-27 2005-05-19 Yasuharu Noisshiki 低血液透過性医用材料
JP2005261867A (ja) * 2004-02-18 2005-09-29 Ube Ind Ltd 管状の人工器官
WO2015080143A1 (ja) * 2013-11-29 2015-06-04 東レ株式会社 人工血管
WO2015122429A1 (ja) * 2014-02-12 2015-08-20 東レ株式会社 人工血管
JP2017506921A (ja) * 2014-02-21 2017-03-16 ヒーリオニクス・コーポレイションＨｅａｌｉｏｎｉｃｓ Ｃｏｒｐｏｒａｔｉｏｎ 血管移植片およびその開存性を維持する方法
WO2019208262A1 (ja) * 2018-04-26 2019-10-31 東レ株式会社 筒状織物およびこれを用いた医療用基材

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