WO2022209633A1 - Artificial blood vessel - Google Patents

Artificial blood vessel 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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Prior art keywords
layer
blood vessel
artificial blood
inner layer
microfibers
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PCT/JP2022/010044
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French (fr)
Japanese (ja)
Inventor
公正 数野
遼平 小林
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テルモ株式会社
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Priority to JP2023510755A priority Critical patent/JPWO2022209633A1/ja
Publication of WO2022209633A1 publication Critical patent/WO2022209633A1/en

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    • 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.

Abstract

An artificial blood vessel (1), in which the inside thereof is endothelialized with good efficiency while strength of the artificial blood vessel is maintained, has a tubular inner layer (11) which is a fabric comprising microfibers having a single fiber diameter of 7 µm or less as the main material thereof, and a tubular reinforcing layer (14) that is applied or bonded to an outer surface of the inner layer (11), the microfibers being exposed over the entire inner surface of the inner layer (11).

Description

人工血管artificial blood vessel
　本発明は、人工血管に関する。 The present invention relates to artificial blood vessels.
　種々の疾病などにより、生体の血管、特に大動脈のような太い血管を人工血管に置き換える必要がある場合がある。 Due to various diseases, it may be necessary to replace the blood vessels of the body, especially large blood vessels such as the aorta, with artificial blood vessels.
　このような場合に用いられる人工血管は、血液を移送できるのみならず、術後に人工血管の内側が内皮細胞によって被覆される内皮化が生じることが望ましい。 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.
　この点に関し、経糸に単糸繊度１．０ｄｔｅｘ以上の太い弾性糸を用い、緯糸に経糸より細い糸を用いて織り上げた織物を用いた人工血管が提案されている（例えば、特許文献１）。しかしながら、この技術では、人工血管としての強度を保つために、経糸に単糸繊度が１．０ｄｔｅｘ以上の太い弾性糸を用いた内層筒状織物と、緯糸にも太い糸を用いた外層筒状織物とを二重織で重ねた多重筒状織物構造を採用している。このため、人工血管の内面に露出する細い糸の量が限られ、人工血管の内側の内皮化は十分とはいえなかった。 In this regard, 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). However, in this technique, in order to maintain the strength as an artificial blood vessel, 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.
国際公開第２０１６／１９０２０２号WO2016/190202
　そこで本発明は、人工血管としての強度を保ちつつ、効率よく内側が内皮化される人工血管を提供することを目的とする。 Therefore, 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.
　本発明は、単糸径が７μｍ以下のマイクロ繊維を主材料とした布帛である筒状の内層と、前記内層の外面に塗布または貼り合わされた筒状の補強層と、を有し、前記マイクロ繊維が、前記内層の内面の全体に渡って露出している、人工血管である。 The present invention has a cylindrical inner layer that is a fabric mainly made of microfibers having a single yarn diameter of 7 μm 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.
　本発明によれば、人工血管としての強度を保ちつつ、効率よく内側が内皮化される人工血管を提供することができる。 According to the present invention, it is possible to provide an artificial blood vessel whose inner side is efficiently endothelialized while maintaining strength as an artificial blood vessel.
人工血管を示す模式図である。It is a schematic diagram which shows an artificial blood vessel. 人工血管の縫合保持強度の測定の際にステンレスワイヤを貫通させる位置を示す模式図である。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. 取り出した人工血管の分割方法を示す図である。It is a figure which shows the division|segmentation method of the taken-out artificial blood vessel.
　本発明は、単糸径が７μｍ以下のマイクロ繊維を主材料とした布帛である筒状の内層と、前記内層の外面に塗布または貼り合わされた筒状の補強層と、を有し、前記マイクロ繊維が、前記内層の内面の全体に渡って露出している、人工血管である。本発明の人工血管によれば、内層に単糸径が７μｍ以下のマイクロ繊維を主材料として用い、このマイクロ繊維が内層の内面の全体に渡って露出している構造とすることで、内層と血管内皮細胞との馴染みがよくなり、内皮細胞の付着性が改善される。また、外側に補強層を用いることにより人工血管としての強度が向上しうる。 The present invention has a cylindrical inner layer that is a fabric mainly made of microfibers having a single yarn diameter of 7 μm 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. According to the artificial blood vessel of the present invention, microfibers having a single yarn diameter of 7 μm 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. In addition, strength as an artificial blood vessel can be improved by using a reinforcing layer on the outside.
　以下、本発明の一実施形態に係る人工血管を詳細に説明する。 The artificial blood vessel according to one embodiment of the present invention will be described in detail below.
　図１は、本実施形態に係る人工血管１を示す図である。図１（Ａ）は人工血管１の斜視図であり、図１（Ｂ）は人工血管１の図１（Ａ）におけるＡＡ線断面図である。 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, and FIG. 1(B) is a cross-sectional view of the artificial blood vessel 1 taken along line AA in FIG. 1(A).
　図１（Ａ）に示すように、人工血管１は、長手方向に連続する蛇腹形状をなす。人工血管１の蛇腹の一つをクリンプＣＲという。なお、図１（Ａ）におけるＡＡ線は蛇腹の谷の部分を通る線である。 As shown 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.
　図１（Ｂ）に示すように、人工血管１は、筒状の内層１１と、内層１１の外面に配置された筒状の補強層１４とを有する。好ましい実施形態において、補強層１４は、遮水層１２、および外層１３を有する。好ましい実施形態において、人工血管１は、内層１１、遮水層１２、および外層１３の三層構造をなす。好ましい実施形態において、人工血管１は、内径がφ１の中空の管状構造物である。 As shown in FIG. 1(B), 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 . In a preferred embodiment, reinforcing layer 14 has impermeable layer 12 and outer layer 13 . In a preferred embodiment, the vascular prosthesis 1 has a three-layer structure of an inner layer 11 , an impervious layer 12 and an outer layer 13 . In a preferred embodiment, the artificial blood vessel 1 is a hollow tubular structure with an inner diameter of φ1.
　（内層）
　内層１１は、単糸径が７μｍ以下のマイクロ繊維を主材料として含む布帛であり、筒状の形状を有する。マイクロ繊維の材質は特に制限されないが、例えばポリエステルなどの柔軟性を有する合成樹脂繊維が挙げられる。ポリエステルとしては、例えばポリエチレンテレフタレート（ＰＥＴ）、ポリブチレンテレフタレート（ＰＢＴ）などが好ましく用いられうる。 (inner layer)
The inner layer 11 is a fabric containing microfibers having a single yarn diameter of 7 μm 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. As polyester, for example, polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and the like can be preferably used.
　布帛には、織物、編物、不織布などが含まれ、いずれも使用可能であるが、本発明の人工血管１の内層１１としては、編物が好適である。内層１１を編物とすることにより、織物のように経糸に太い糸を使用する必要がなくなるため、人工血管の内面に露出するマイクロ繊維の割合を大きくして、内皮化の効率を高めることができる。 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. 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. .
　＜内層の単糸径＞
　内層１１は、単糸径が７μｍ以下のマイクロ繊維を主材料として含む。中でも、上記マイクロ繊維の単糸径は３μｍ以上であることが好ましい。すなわち、内層１１は、単糸径が３μｍ以上７μｍ以下のマイクロ繊維を主材料として形成されることが好ましい。ここでマイクロ繊維とは、単糸繊度が１．０ｄｔｅｘ未満の繊維を指す。なお、本明細書中、マイクロ繊維の単糸径は、平面上に切り開いた基材をＳＥＭ観察し、ＣＣＤ計測ツールにて異なる繊維の外径を一定数（２０ヶ所）測定して得られた値の平均値を用いる。 <Single yarn diameter of inner layer>
The inner layer 11 contains microfibers having a single yarn diameter of 7 μm or less as a main material. Above all, it is preferable that the single yarn diameter of the microfiber is 3 μm or more. That is, the inner layer 11 is preferably formed mainly of microfibers having a single yarn diameter of 3 μm or more and 7 μm or less. Here, microfibers refer to fibers having a single filament fineness of less than 1.0 dtex. In this specification, 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.
　内層１１の主材料としてのマイクロ繊維の単糸径が７μｍより太いと、人工血管の内側が内皮細胞によって被覆される内皮化の効率が悪化する。また、内層１１の主材料としてのマイクロ繊維の単糸径が３μｍ以上であると、人工血管としての強度、特に縫合保持強度により優れるため好ましい。 If the single thread diameter of the microfiber as the main material of the inner layer 11 is thicker than 7 μm, 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 μm or more because the strength as the artificial blood vessel, particularly the suture holding strength, is excellent.
　ここで、主材料として含むとは、その材料を５０質量％以上含むことをいう。好ましくは、内層１１は、上記の所定の単糸径を有するマイクロ繊維を５０質量％超含み、より好ましくは７０質量％以上含み、さらに好ましくは９０質量％以上含み、さらにより好ましくは９５質量％以上含み、特に好ましくは９９質量％以上含む。最も好ましくは、内層１１は、上記の所定の単糸径を有するマイクロ繊維からなるものである（所定の単糸径を有するマイクロ繊維の割合が１００質量％である）。 Here, "containing as the main material" means containing 50% by mass or more of the material. Preferably, 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. Most preferably, 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).
　上記マイクロ繊維の形態としては特に制限されないが、強度や物性の均一性、及び柔軟性から、マルチフィラメントの形態で用いることが好ましい。上記マイクロ繊維の捲縮はあってもなくてもよい。 Although the form of the 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.
　上記マイクロ繊維の繊度は、特に制限されないが、５～２００ｄｔｅｘであることが好ましい。５ｄｔｅｘ以上であれば強度により優れる。また、２００ｄｔｅｘ以下であれば柔軟性に優れるため好ましい。 Although 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.
　上記マイクロ繊維の単糸繊度は、１．０ｄｔｅｘ未満であればよいが、好ましくは０．５ｄｔｅｘ以下である。上記範囲であると内皮細胞の付着性がより向上しうる。 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.
　なお、繊度は、ＪＩＳ　Ｌ　１０１３（２０１０）８．３．１　Ａ法にしたがって、所定加重０．０４５ｃＮ／ｄｔｅｘで測定した正量繊度である。また、これを単糸数で除することにより単糸繊度を算出することができる。 It should be noted that 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.
　＜透水率＞
　内層１１の透水率は、特に制限されないが、例えば３０００～７５００ｍｌ／ｍｉｎ／ｃｍ２であり、６８００～７１００ｍｌ／ｍｉｎ／ｃｍ２であることが望ましい。 <Permeability>
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 .
　上記範囲であると、人工血管の内側が内皮細胞によって被覆される内皮化の効率がより向上しうる。 Within the above range, the efficiency of endothelialization in which the inner side of the artificial blood vessel is covered with endothelial cells can be further improved.
　ここで透水率は、次のようにして測定する。すなわち、管状の内層１１の一端を塞ぎ、他端から逆浸透膜でろ過した水を内壁に１６ｋＰａの水圧がかかるように所定時間注入し、管壁から漏れ出した水の管壁単位面積当たり単位時間当たりの量を計算して求める。なお、遮水層、外層などの他の層の透水率も同様の方法で測定することができる。 Here, 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.
　内層の厚さは特に制限されず、適宜調整することができる。 The thickness of the inner layer is not particularly limited and can be adjusted as appropriate.
　本発明の人工血管においては、上記の所定の単糸径を有するマイクロ繊維が、内層の内面の全体に渡って露出しているものである。「全体に渡って露出する」とは、筒状の構造体において端部から中心部を通って他方の端部まで、構造体中の位置によらず露出していることをいう。具体的な形態としては、内層の内表面の全体にわたって、当該マイクロ繊維を主材料とする布帛の表面が露出している形態が挙げられる。 In the vascular prosthesis of the present invention, 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.
　なお、ゼラチンなどの生分解性コーティングが内層の内表面に塗布されていてもよい。この場合、生体への埋植後に生分解性コーティングが分解して、上記の所定の単糸径を有するマイクロ繊維が内層の内面の全体に渡って露出するようになるため、本発明の範囲に含まれる。 A biodegradable coating such as gelatin may be applied to the inner surface of the inner layer. In this case, 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.
　本発明の好ましい実施形態においては、内層１１は、上記の所定の単糸径を有するマイクロ繊維のみによって形成される。内層１１が上記の所定の単糸径を有するマイクロ繊維のみにより形成されることにより、これよりも単糸径の大きい繊維を併用する場合と比較して、人工血管の内面全体により多くのマイクロ繊維が露出し、内皮化の効率をさらに高めることができる。 In a preferred embodiment of the present invention, the inner layer 11 is formed only of microfibers having the above-mentioned predetermined single thread diameter. By forming the inner layer 11 only from the microfibers having the above-described predetermined single yarn diameter, more microfibers are formed on the entire inner surface of the vascular prosthesis compared to the case of using fibers with a larger single yarn diameter. are exposed and can further enhance the efficiency of endothelialization.
　（補強層）
　本発明の人工血管１は、内層１１の外面に塗布または貼り合わされた補強層１４を有する。補強層１４としては、遮水性および弾性を有する樹脂によって形成される遮水層１２、単糸径が１０μｍ以上５５μｍ以下の繊維を主材料とした布帛の層を含む外層１３、またはこれらの双方を含むことが好ましい。上記遮水層を設けることで、人工血管に柔軟性を与え、細胞や体液の侵入を防止することができる。また、上記外層を設けることで強度を確保することができる。特には、内層１１の外面に、遮水層１２と外層１３とをこの順で有することが好ましい。 (reinforcing layer)
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 . As the reinforcing layer 14, 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 μm or more and 55 μm or less, or both of them. preferably included. By providing the waterproof layer, flexibility can be imparted to the artificial blood vessel, and intrusion of cells and body fluids can be prevented. In addition, strength can be ensured by providing the outer layer. In particular, it is preferable to have the impermeable layer 12 and the outer layer 13 in this order on the outer surface of the inner layer 11 .
　なお、一般的なステントグラフトのような金属製の網目状の構造体は、本発明における補強層には含まないものとする。 It should be noted that a metal mesh structure such as a general stent graft is not included in the reinforcing layer in the present invention.
　（遮水層）
　遮水層１２は、遮水性および弾性を有する樹脂によって形成されることが好ましい。弾性を有する樹脂としては、例えばスチレン系エラストマーまたはその混合物が挙げられるがこれに限られない。また、ゼラチンやコラーゲンを用いることもできる。 (impermeable layer)
The impermeable layer 12 is preferably made of resin having impermeability and elasticity. Examples of elastic resins include, but are not limited to, styrene-based elastomers and mixtures thereof. Gelatin or collagen can also be used.
　スチレン系エラストマーとしては特に限定されないが、スチレンを主成分とする部分と、ブタジエン及び／又はイソプレン及び／又はそれらの水素添加物からなる部分とから構成された共重合体を主成分とするものが挙げられる。 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.
　遮水層は、例えば、スチレン系エラストマーに可塑剤であるスクラワンを適量混合して得られた材料を、常法、例えば、熱プレス機でシート状に成形することにより作製することができる。このように得られた遮水層を、例えば熱融着により内層の外面に貼り合わせることができる。 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.
　ゼラチンやコラーゲンを用いる場合は、これらのゲルを内層の外面に塗布することで遮水層を形成することができる。 When gelatin or collagen is used, a waterproof layer can be formed by applying these gels to the outer surface of the inner layer.
　遮水層１２は遮水性を有するように形成される。ここで遮水性を有するとは、上述の透水率が１．０ｍｌ／ｍｉｎ／ｃｍ２以下であることをいう。 The impermeable layer 12 is formed to have impermeability. Here, having water impermeability means that the above-mentioned water permeability is 1.0 ml/min/cm 2 or less.
　遮水層の厚さは特に制限されず、適宜調整することができる。 The thickness of the impermeable layer is not particularly limited and can be adjusted as appropriate.
　（外層）
　外層１３は、単糸径が１０μｍ以上５５μｍ以下の繊維を主材料とした布帛の層を有することが好ましい。布帛としては、例えばポリエステルなどの柔軟性を有する合成樹脂繊維を含んで形成される布帛が用いられうる。 (outer layer)
The outer layer 13 preferably has a layer of fabric whose main material is fibers having a single yarn diameter of 10 μm or more and 55 μm or less. As the fabric, for example, a fabric containing flexible synthetic resin fibers such as polyester can be used.
　布帛には、織物、編物、不織布などが含まれるが、人工血管１の外層１３としては編物が好適である。 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 .
　＜外層の単糸径＞
　外層１３は、特に制限されないが、単糸径が１０μｍ以上５５μｍ以下の繊維を主材料とした布帛の層を有することが好ましい。中でも、上記層としては、単糸径が１３μｍの繊維を主材料として形成される編物から構成される層が好適である。 <Single yarn diameter of outer layer>
Although 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 μm or more and 55 μm or less. Among them, a layer composed of a knitted fabric mainly composed of fiber having a single yarn diameter of 13 μm is preferable as the layer.
　繊維の単糸径が５５μｍ以下であると、人工血管としての柔軟性が向上しうる。また１０μｍ以上であると、人工血管としての強度が向上しうる。 When the single fiber diameter of the fiber is 55 μm or less, the flexibility as an artificial blood vessel can be improved. Further, when the thickness is 10 μm or more, the strength as an artificial blood vessel can be improved.
　繊維の捲縮はあってもなくてもよい。 The fibers may or may not be crimped.
　なお、外層１３は、遮水性、強度、生体適合性などを向上させる目的で、上記の単糸径が１０μｍ以上５５μｍ以下の繊維を主材料とした布帛の層の外側に、コーティング層をさらに有していてもよい。コーティング層の具体的な形態は特に制限されない。なお、コーティング層を有する含む場合、コーティング層の部分を含めて外層とする。 In addition, 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 μm or more and 55 μm 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.
　外層の透水率は特に制限されず、適宜調整することができる。 The water permeability of the outer layer is not particularly limited and can be adjusted as appropriate.
　外層の厚さは特に制限されず、適宜調整することができる。 The thickness of the outer layer is not particularly limited and can be adjusted as appropriate.
　＜人工血管の内径＞
　太い血管を代替する人工血管では、内皮化を促進する必要性が高い。このため、人工血管の内径となる内層の内径は、好ましくは５ｍｍ以上であり、より好ましくは８ｍｍ以上である。上記範囲であると本発明の効果がより顕著に得られうる。 <Inner Diameter of Artificial Blood Vessel>
There is a strong need to promote endothelialization in artificial blood vessels that replace thick blood vessels. Therefore, 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.
　本発明の人工血管は、強度に優れるとともに、血管内皮細胞との親和性に優れる。そのため、損傷等を受けた血管の再建、修復または代替に好適に使用されるほか、ステントのように血管の狭窄した部位に挿入して狭窄を改善するために用いることができる。 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.
　本発明の効果を、以下の実施例および比較例を用いて説明する。ただし、本発明の技術的範囲が以下の実施例のみに制限されるわけではない。 The effects of the present invention will be explained using the following examples and comparative examples. However, the technical scope of the present invention is not limited only to the following examples.
　＜縫合保持強度＞
　実施例１、２、および比較例１、２として、下記表１に記載の人工血管を準備し、人工血管としての強度の指標の１つである縫合保持強度を確認した。人工血管は内径８ｍｍ、長さ約５ｃｍの筒状の構造とした。なお、比較例１は内層のみ、実施例１は、内層の外面に補強層として遮水層を有し、実施例２および比較例２は内層の外面に補強層として遮水層および外層をこの順に有する。各実施例、比較例において内層および外層は編物を使用し、遮水層には、スチレン系エラストマーに可塑剤であるスクワランを適量混合して得られた材料を用いた。また、各実施例、比較例において、内層および外層は、それぞれ、単一の繊維を用いた編物であり、表１中の材質、単糸径、繊度、単糸繊度、捲縮は、それぞれ、当該単一の繊維についての値である。 <Suture retention strength>
As Examples 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, and 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. In each example and comparative example, 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. In addition, in each example and comparative example, 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.
　縫合保持強度は、ＩＳＯ　７１９８．８．８を参照して、以下の手順で行った：
　１．図２に示すように、試験片の断端より２ｍｍの部位に３－０ステンレスワイヤを貫通させた；
　２．基材とワイヤを固定し、２００ｍｍ／ｍｉｎの速度で引張試験を実施した（ｎ＝３）；
　３．最大荷重を縫合保持強度とした。 Suture retention strength was performed with reference to ISO 7198.8.8 with the following procedure:
1. As shown in FIG. 2, a 3-0 stainless steel wire was passed through a portion 2 mm from the stump of the test piece;
2. The base material and the wire were fixed, and a tensile test was performed at a speed of 200 mm/min (n = 3);
3. The maximum load was defined as the suture holding strength.
　結果を下記表１に示す。縫合保持強度が８Ｎ以上であれば人工血管として十分な強度を有しているものと考えられる。なお、縫合保持強度は、図２に示すように１つの試験片を用いて３箇所測定し、その平均値および標準偏差を求めた。 The results are shown in Table 1 below. If the suture holding strength is 8N or more, it is considered that the artificial blood vessel has sufficient strength. The suture holding strength was measured at three points using one test piece as shown in FIG. 2, and the average value and standard deviation thereof were obtained.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　上記表１に示されるように、内層と補強層とを有する実施例１、２、および比較例２の人工血管は十分な縫合保持強度を示すことがわかった。これに対して、補強層を有さない比較例１では、強度が不十分であった。 As shown in Table 1 above, it was found that the artificial blood vessels of Examples 1, 2, and Comparative Example 2 having an inner layer and a reinforcing layer exhibited sufficient suture holding strength. On the other hand, in Comparative Example 1, which does not have a reinforcing layer, the strength was insufficient.
　＜内皮化の確認＞
　実施例３～６、および比較例３として、下記表２に記載の人工血管を準備し、人工血管の内壁の内皮化の進行を確認した。人工血管は内径８ｍｍ、長さ約５ｃｍの筒状の構造とした。各実施例、比較例の人工血管は、内層の外面に補強層として遮水層および外層をこの順に有する。各実施例、比較例において内層および外層は編物を使用し、遮水層には、スチレン系エラストマーに可塑剤であるスクワランを適量混合して得られた材料を用いた。また、各実施例、比較例において、内層および外層は、それぞれ、単一の繊維を用いた編物であり、表２中の材質、単糸径、繊度、単糸繊度、捲縮は、それぞれ、当該単一の繊維についての値である。 <Confirmation of endothelialization>
As 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. In each example and comparative example, 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. In addition, in each example and comparative example, 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.
　（実験の条件）
・被験体：サル
・体重：５ｋｇ以上
・人工血管：上記で準備した実施例３～６、比較例３の人工血管
・埋植期間：４週間。 (Experimental conditions)
Subject: Monkey Weight: 5 kg or more Artificial blood vessel: Artificial blood vessel prepared in Examples 3 to 6 and Comparative Example 3 Implantation period: 4 weeks.
　（内皮化の確認）
　被験体の大動脈の一部を人工血管によって置き換え、埋植期間経過後に取り出して内皮化を確認した。 (Confirmation of endothelialization)
A portion of the subject's aorta was replaced with an artificial blood vessel and removed after the implantation period to confirm endothelialization.
　図３は、取り出した人工血管の分割方法を示す図である。図３に示すように、所定の長さを切り出し、まず縦に２分割し、さらに縦に２分割してＡ～Ｄの小片を作成した。 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.
　これらの小片の内壁を肉眼によって観察することにより、また切片を染色して観察することにより、内皮化の程度を観察した。 The degree of endothelialization was observed by observing the inner walls of these small pieces with the naked eye and by observing stained sections.
　観察した結果を、以下式１に基づいて数値化した。
式１：（血管内皮細胞被覆率（％））＝（（血管内皮細胞に被覆されたクリンプ数）／（総クリンプ数））×１００
　ただし、Ａ～ＤのクリンプＣＲの総数を総クリンプ数とした。 The observed results were quantified based on Equation 1 below.
Formula 1: (vascular endothelial cell coverage (%)) = ((number of crimps covered by vascular endothelial cells)/(total number of crimps)) x 100
However, the total number of crimp CRs A to D was taken as the total number of crimps.
　血管内皮細胞被覆率が４５％を超えるものを合格とする。結果を下記表２に示す。 Those with a vascular endothelial cell coverage rate of over 45% are passed. The results are shown in Table 2 below.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　上記表２に示されるように、内層として単糸径が７μｍ以下のマイクロ繊維を用いた実施例３～６の人工血管はいずれも、血管内皮細胞被覆率が４５％超であり、内皮化が効率的に進行していることが確認された。一方で内層に単糸径が７μｍを超える繊維を用いた比較例３の人工血管では、内皮化が十分に進行しなかった。 As shown in Table 2 above, all of the artificial blood vessels of Examples 3 to 6 using microfibers having a single yarn diameter of 7 μm or less as the inner layer had a vascular endothelial cell coverage rate of more than 45%, indicating that endothelialization occurred. Efficient progress was confirmed. On the other hand, in the vascular prosthesis of Comparative Example 3, in which fibers with a single filament diameter exceeding 7 μm were used in the inner layer, endothelialization did not proceed sufficiently.
　また、内層１１を編物とすることにより、織物のように経糸に太い糸を使用する必要がなくなるため、人工血管の内面に露出するマイクロ繊維の割合を大きくして、内皮化の効率を高めることができる。 In addition, 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.
　さらに、内層１１を同一のマイクロ繊維のみにより構成することで、人工血管の内面全体にマイクロ繊維が露出し、内皮化の効率をさらに高めることができる。 Furthermore, by forming the inner layer 11 only from the same microfibers, the microfibers are exposed on the entire inner surface of the artificial blood vessel, and the efficiency of endothelialization can be further increased.
　本出願は、２０２１年３月３０日に出願された日本国特許出願第２０２１－０５７５９０号に基づいており、その開示内容は、参照により全体として引用されている。 This application is based on Japanese Patent Application No. 2021-057590 filed on March 30, 2021, the disclosure of which is incorporated by reference in its entirety.
１　人工血管
１１　内層
１２　遮水層
１３　外層
１４　補強層
ＣＲ　クリンプ
φ１　内径。 1 artificial blood vessel 11 inner layer 12 impervious layer 13 outer layer 14 reinforcing layer CR crimp φ1 inner diameter.

Claims (7)

  1. 　単糸径が７μｍ以下のマイクロ繊維を主材料とした布帛である筒状の内層と、
    　前記内層の外面に塗布または貼り合わされた筒状の補強層と、を有し、
    　前記マイクロ繊維が、前記内層の内面の全体に渡って露出している、人工血管。     a cylindrical inner layer that is a fabric mainly composed of microfibers having a single yarn diameter of 7 μm or less;
    a cylindrical reinforcing layer applied or bonded to the outer surface of the inner layer,
    A vascular prosthesis, wherein the microfibers are exposed over the entire inner surface of the inner layer.
  2. 　前記マイクロ繊維が、３μｍ以上の単糸径を有する、請求項１に記載の人工血管。 The artificial blood vessel according to claim 1, wherein the microfiber has a single thread diameter of 3 μm or more.
  3. 　前記補強層が、単糸径が１０μｍ以上５５μｍ以下の繊維を主材料とした布帛の層を含む外層を有する、請求項１または２に記載の人工血管。 The artificial blood vessel according to claim 1 or 2, wherein the reinforcing layer has an outer layer containing a layer of fabric whose main material is fibers having a single yarn diameter of 10 µm or more and 55 µm or less.
  4. 　前記補強層が、遮水性および弾性のある樹脂によって形成される遮水層を有する、請求項１～３のいずれか１項に記載の人工血管。 The artificial blood vessel according to any one of claims 1 to 3, wherein the reinforcing layer has a water-impermeable layer formed of a resin having water-imperviousness and elasticity.
  5. 　前記内層は、編物である、請求項１～４のいずれか１項に記載の人工血管。 The artificial blood vessel according to any one of claims 1 to 4, wherein the inner layer is a knitted fabric.
  6. 　前記内層は、前記マイクロ繊維のみによって形成されている、請求項１～５のいずれか１項に記載の人工血管。 The artificial blood vessel according to any one of claims 1 to 5, wherein the inner layer is formed only of the microfibers.
  7. 　前記内層の内径が５ｍｍ以上である、請求項１～６のいずれか１項に記載の人工血管。 The artificial blood vessel according to any one of claims 1 to 6, wherein the inner layer has an inner diameter of 5 mm or more.
PCT/JP2022/010044 2021-03-30 2022-03-08 Artificial blood vessel WO2022209633A1 (en)

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* Cited by examiner, † Cited by third party
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JPS6077764A (en) * 1983-10-05 1985-05-02 東レ株式会社 Artificial blood vessel
JP2005124959A (en) * 2003-10-27 2005-05-19 Yasuharu Noisshiki Low blood permeable medical material
JP2005261867A (en) * 2004-02-18 2005-09-29 Ube Ind Ltd Tubular artificial organ
WO2015080143A1 (en) * 2013-11-29 2015-06-04 東レ株式会社 Vascular prosthesis
WO2015122429A1 (en) * 2014-02-12 2015-08-20 東レ株式会社 Artificial blood vessel
JP2017506921A (en) * 2014-02-21 2017-03-16 ヒーリオニクス・コーポレイションＨｅａｌｉｏｎｉｃｓ Ｃｏｒｐｏｒａｔｉｏｎ Vascular graft and method for maintaining its patency
WO2019208262A1 (en) * 2018-04-26 2019-10-31 東レ株式会社 Tubular fabric and base material for medical use using same

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6077764A (en) * 1983-10-05 1985-05-02 東レ株式会社 Artificial blood vessel
JP2005124959A (en) * 2003-10-27 2005-05-19 Yasuharu Noisshiki Low blood permeable medical material
JP2005261867A (en) * 2004-02-18 2005-09-29 Ube Ind Ltd Tubular artificial organ
WO2015080143A1 (en) * 2013-11-29 2015-06-04 東レ株式会社 Vascular prosthesis
WO2015122429A1 (en) * 2014-02-12 2015-08-20 東レ株式会社 Artificial blood vessel
JP2017506921A (en) * 2014-02-21 2017-03-16 ヒーリオニクス・コーポレイションＨｅａｌｉｏｎｉｃｓ Ｃｏｒｐｏｒａｔｉｏｎ Vascular graft and method for maintaining its patency
WO2019208262A1 (en) * 2018-04-26 2019-10-31 東レ株式会社 Tubular fabric and base material for medical use using same

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