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WO2013172021A1 - Vaisseau sanguin artificiel, et procédé de fabrication de celui-ci - Google Patents

Vaisseau sanguin artificiel, et procédé de fabrication de celui-ci Download PDF

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Publication number
WO2013172021A1
WO2013172021A1 PCT/JP2013/003078 JP2013003078W WO2013172021A1 WO 2013172021 A1 WO2013172021 A1 WO 2013172021A1 JP 2013003078 W JP2013003078 W JP 2013003078W WO 2013172021 A1 WO2013172021 A1 WO 2013172021A1
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WO
WIPO (PCT)
Prior art keywords
blood vessel
artificial blood
silk fibroin
silk
base
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.)
Ceased
Application number
PCT/JP2013/003078
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English (en)
Japanese (ja)
Inventor
朝倉　哲郎
義秀 高木
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.)
FUKUI WARP KNITTING Co Ltd
Tokyo University of Agriculture and Technology NUC
University of Tokyo NUC
Original Assignee
FUKUI WARP KNITTING Co Ltd
Tokyo University of Agriculture and Technology NUC
University of Tokyo NUC
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 FUKUI WARP KNITTING Co Ltd, Tokyo University of Agriculture and Technology NUC, University of Tokyo NUC filed Critical FUKUI WARP KNITTING Co Ltd
Priority to JP2014515498A priority Critical patent/JP6146718B2/ja
Publication of WO2013172021A1 publication Critical patent/WO2013172021A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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

Definitions

  • the present invention relates to an artificial blood vessel and a method for producing the same, and more particularly to an artificial blood vessel that can be maintained for a long period of time and a method for producing the same.
  • the artificial blood vessel is used, for example, for a purpose of temporarily securing a blood flow path during surgery or a use as a substitute blood vessel for a diseased blood vessel.
  • Polyester, polytetrafluoroethylene (PTFE) and the like have been developed as materials for such artificial blood vessels.
  • a knitted or woven fabric using polyester yarn, which is knitted into a tubular shape is commercially available.
  • an artificial blood vessel using polyester or PTFE has a drawback that the patency rate is remarkably lowered in the case of a so-called small-diameter artificial blood vessel having an inner diameter of less than 6 mm, and has not been put into practical use.
  • the patency rate means the rate at which the artificial blood vessel is patent when transplanted in a living body. That is, a low patency rate means that the artificial blood vessel is easily clogged.
  • an artificial blood vessel using silk used as a surgical suture has been developed as an alternative material for polyester.
  • a small-diameter artificial blood vessel in which a multilayered tubular structure formed by braiding silk fibroin yarn in multiple layers is coated with silk fibroin see, for example, Patent Document 1
  • silk fibroin fiber is knitted, assembled, Sericin-removed tubular structure obtained by smoothing the outer wall surface of the tubular structure wound by one or more methods selected from woven and entangled
  • Patent Document 2 silk fibroin dissolution Silk nanofibers formed by electrospinning using a liquid are collected around a rotating support rod covered with a resin tube, and then the support rod is pulled out to produce a tubular structure (Patent Document) 3) is known.
  • the present invention has been made in view of the above circumstances, and an object thereof is to provide an artificial blood vessel that can be maintained for a long period of time and a method for manufacturing the same.
  • the inventors of the present invention have intensively studied to solve the above-mentioned problems.
  • the silk fibroin fiber is formed into a tubular shape by double raschel knitting, and the surface is thickly covered with silk fibroin.
  • the inventors have found that the above-described problems can be solved by having a water content of 5%, and have completed the present invention.
  • a plurality of silk fibroin fibers having silk sericin attached to the surface are combined to form a silk fibroin fiber bundle, the silk fibroin fiber bundle is knitted into a tubular shape by double raschel knitting, and the silk sericin is removed.
  • the present invention resides in (2) the artificial blood vessel according to the above (1), wherein the water permeability measured according to ISO 7198 is 70 to 240 ml / cm 2 / min.
  • the present invention resides in (3) the artificial blood vessel according to the above (1) or (2) having an elastic modulus of 0.05 to 0.09 N / mm 2 .
  • the present invention provides: (4) the artificial twist according to any one of (1) to (3), wherein the silk fibroin fiber is subjected to a lower twist, and the silk fibroin fiber bundle is subjected to an upper twist. It exists in blood vessels.
  • the present invention resides in (5) the artificial blood vessel according to the above (4), wherein the number of twists of the upper twist is smaller than the number of twists of the lower twist.
  • the present invention is (6) the method for producing an artificial blood vessel according to any one of claims 1 to 5, wherein raw silk composed of silk thread is scoured, and a portion of silk sericin remains on the surface of silk fibroin.
  • a scouring step to produce a silk fibroin fiber a yarn making step to combine a plurality of silk fibroin fibers into a silk fibroin fiber bundle, a knitting step to knitting the silk fibroin fiber bundle into a tubular body by double raschel knitting,
  • the removal process of silk sericin remaining in the tubular body to remove the base and the sponge-like covering portion covered with silk fibroin on the surface of the base portion, the thickness of the covering portion of the front portion of the base portion is 0.8 mm or more
  • forming a temporary artificial blood vessel and an immersion step of immersing the temporary artificial blood vessel in pure water, and immersing the temporary artificial blood vessel in a wet state after the coating step.
  • the present invention resides in the method for producing an artificial blood vessel according to the above (6), wherein (7) the dipping step is performed by immersing the temporary artificial blood vessel in pure water for 1 hour or more.
  • the present invention resides in the method for producing an artificial blood vessel according to the above (6) or (7), wherein (8) the dipping step is performed until immediately before the transplantation of the artificial blood vessel.
  • the present invention resides in (9) the method for producing an artificial blood vessel according to any one of the above (6) to (8), wherein the coating step is performed by immersing the base in a silk fibroin solution and freeze-drying. .
  • the present invention provides the method for producing an artificial blood vessel according to any one of the above (6) to (8), wherein (10) the coating step is performed by coating the base with silk fibroin sponge using a hole source material. Exist.
  • the artificial blood vessel of the present invention can be maintained for a long time by setting the moisture content to 60% or more. Although it is not clear why it can be maintained for a long period of time, by keeping the moisture content within the above range, it prevents the sponge-like coating part coated at the time of living transplantation from peeling off from the base surface at the time of transplanting. In addition, it is presumed that oxygen, moisture, and biological material can smoothly pass through the wall of the sponge-like covering portion of the artificial blood vessel after transplantation.
  • the inner surface of the double raschel knitted base is also covered with the covering portion, so that the endothelial cells are easily fixed and thrombus is hardly formed.
  • the artificial blood vessel is not easily refracted even when bent into a U shape.
  • the elastic modulus is 0.05 to 0.09 N / mm 2 , it is more difficult to refract even when bent into a U shape.
  • the non-cracking property means that, for example, the generation of strain and cracks that occur when the moisture content of the artificial blood vessel is temporarily reduced (for example, less than 60%) is suppressed.
  • the artificial blood vessel of the present invention has an advantage that when the water permeability measured according to ISO 7198 is 70 to 240 ml / cm 2 / min, it can be transplanted smoothly and the organization is improved after transplantation.
  • the artificial blood vessel of the present invention when silk fibroin fibers are subjected to a lower twist, and silk fibroin fiber bundles are subjected to an upper twist, an appropriate focusing effect between the silk fibroin fibers can be obtained, and during knitting It can also suppress that a cross section collapses. Further, since contact friction is reduced, problems such as yarn breakage and fluffing can be prevented. At this time, when the number of twists of the upper twist is less than the number of twists of the lower twist, a silk fibroin fiber bundle in a stable state without rotational torque is obtained.
  • the method for producing an artificial blood vessel of the present invention since the above-described artificial blood vessel is obtained, it can be maintained for a long period of time.
  • the coating portion is thickened, and after the coating step, the immersion step is performed in a state where the temporary artificial blood vessel is kept wet. It is possible to suppress the occurrence of strain and cracks that occur when the amount is reduced (for example, less than 60%). In addition, if an immersion process is performed until just before transplantation of an artificial blood vessel, an artificial blood vessel can be transplanted in a state where generation of strain and cracks is suppressed as much as possible.
  • the immersion of the temporary artificial blood vessel in the pure water in the immersion step is 1 hour or more, the pure water can sufficiently penetrate into the temporary artificial blood vessel, In addition, the resulting artificial blood vessel is difficult to dry.
  • FIG.1 (a) is a perspective view which shows typically the artificial blood vessel concerning this embodiment
  • FIG.1 (b) is an enlarged view which shows the part P of Fig.1 (a).
  • Fig.2 (a) is a schematic diagram which shows the apparatus which measures a (compression) elastic modulus
  • FIG.2 (b) is a photograph of Fig.2 (a).
  • FIG. 3A is a schematic diagram showing an apparatus for measuring the anastomosis retention strength
  • FIG. 3B is a photograph of FIG.
  • FIG. 4 is a schematic diagram showing an apparatus for measuring the porosity.
  • FIG.5 (a) is a schematic diagram which shows the apparatus which measures circumferential-axis intensity
  • FIG.5 (b) is a photograph of Fig.5 (a).
  • FIG. 6 is a flowchart showing a method for manufacturing an artificial blood vessel according to the present embodiment.
  • FIG. 7 is a partial explanatory view showing the positional relationship between the ridges, needles, and knitting yarns of the double raschel machine.
  • FIG. 8 is an enlarged structural diagram showing a double denby structure in double raschel knitting.
  • FIG. 9 is an enlarged structural view showing an inverted half structure in double raschel knitting.
  • FIG. 10 is a solid 13 C DD / MAS spectrum obtained in Evaluation 3 of the example.
  • FIG. 11 is a two-dimensional spectrum of 2 H longitudinal relaxation time (T 1 ) and transverse relaxation time (T 2 ) obtained in Evaluation 4 of the example.
  • FIG. 1A is a perspective view schematically showing an artificial blood vessel according to this embodiment.
  • an artificial blood vessel 10 according to the present embodiment is made of silk fibroin and includes a tubular base 1 and a sponge-like covering 2 covering the surface of the base 1.
  • the artificial blood vessel 10 is configured such that blood circulates in the base 1 by, for example, stitching both ends to the blood vessel.
  • the artificial blood vessel 10 is made of silk fibroin excellent in biocompatibility, when transplanted into the body, the endothelial cells are easily established and thrombus is hardly formed.
  • the base 1 is formed by combining a plurality of silk fibroin fibers into a silk fibroin fiber bundle, and the silk fibroin fiber bundle is knitted into a tubular shape by double raschel knitting.
  • the silk fibroin fiber before being applied to the double raschel machine has a structure in which silk sericin is adhered to the surface, the silk fibroin is protected by the silk sericin. Thereby, for example, during knitting, damage to silk fibroin is suppressed even if there is contact with a guide, a needle or the like, and as a result, a high-quality artificial blood vessel with excellent strength can be obtained.
  • silk sericin is excellent in moisture retention, it plays the role of a lubricant. For this reason, problems such as yarn breakage and fluffing during knitting can also be prevented.
  • a silk fibroin fiber bundle is a bundle of a plurality of silk fibroin fibers, and is knitted into a tubular shape by double raschel knitting using a double raschel machine.
  • double raschel knitting it is possible to obtain fraying difficulty, elasticity, and flexibility that cannot be obtained with a conventional artificial blood vessel made of silk.
  • the base 1 is formed by removing silk sericin after knitting into a tubular shape by double raschel knitting. Details of the manufacturing method will be described later.
  • a silk fibroin fiber is subjected to a lower twist, and a silk fibroin fiber bundle obtained by combining a plurality of silk fibroin fibers is subjected to an upper twist. That is, a plurality of silk fibroin fibers subjected to a lower twist are combined to form a silk fibroin fiber bundle, and an upper twist is applied thereto. Note that the lower twist applied to the silk fibroin fiber and the upper twist applied to the silk fibroin fiber bundle are in opposite directions.
  • the number of twists of the upper twist applied to the silk fibroin fiber bundle is smaller than the number of twists of the lower twist applied to the silk fibroin fiber. In this case, a silk fibroin fiber bundle in a stable state without rotational torque is obtained.
  • the covering portion 2 is obtained by covering the back and front surfaces of the base portion 1 with silk fibroin.
  • silk fibroin when sericin and other fat are contained in silk fibroin, these are removed and used.
  • the removal method is not particularly limited, for example, boiling washing may be performed using Marcel soap.
  • the covering portion 2 is formed by applying silk fibroin to the base portion 1.
  • the silk fibroin aqueous solution passes through the stitches and easily reaches the surface on the back side of the base 1.
  • the surface of the back side of the base 1 becomes smooth, the endothelial cells are more easily fixed and thrombus is less easily formed. Details of the manufacturing method will be described later.
  • the artificial blood vessel 10 includes the sponge-like covering portion 2, the flexibility is improved. For example, even when the artificial blood vessel 10 is bent in a U shape, the bending is maintained and it is difficult to refract. Thereby, even if it is a case where the artificial blood vessel 10 is transplanted in the position which bends, it can suppress that the circulation
  • the thickness of the covering portion 2 is such that the thickness H1 of the covering portion of the front side portion of the base portion is 0.8 mm or more (see FIG. 1B).
  • the thickness H1 of the covering portion on the front side portion of the base is less than 0.8 mm, there is a drawback that the number of holes is reduced and the blocking rate is improved.
  • the artificial blood vessel 10 is non-cracking. That is, generation
  • the artificial blood vessel 10 has a moisture content of 60% or more, preferably 80% or more, and more preferably 90% or more. In particular, a saturated state is most preferable.
  • the moisture content is calculated by dividing a value obtained by subtracting the weight of a sufficiently dried artificial blood vessel from the weight of the water-containing artificial blood vessel by the weight of the water-containing artificial blood vessel. If the water content is less than 60%, there is a disadvantage that it cannot be maintained for a long time.
  • the artificial blood vessel 10 preferably has a water permeability measured according to ISO 7198 of 70 to 240 ml / cm 2 / min.
  • a water permeability measured according to ISO 7198 of 70 to 240 ml / cm 2 / min When the water permeability is less than 70 ml / cm 2 / min%, there is a drawback that organization is difficult to proceed after transplantation compared to the case where the water permeability is within the above range, and the water permeability is 240 ml / cm 2 / min. When it exceeds%, there is a drawback that blood may leak after transplantation, compared with the case where the water permeability is in the above range.
  • the artificial blood vessel 10 preferably has a (compression) elastic modulus of 0.05 to 0.09 N / mm 2 .
  • the (compression) elastic modulus is measured using a pair of compression bases A1 and A2 as shown in FIGS. 2 (a) and 2 (b). That is, a sample P (tubular artificial blood vessel) having a length of 1 cm in the longitudinal direction is placed on the lower compression table A2 so that the longitudinal direction is horizontal, and the upper compression table A1 is set to an operating cell 5N and a descent speed of 2 mm. The value is calculated from the value when the compression table A1 is compressed up to 25% of the inner diameter of the sample P.
  • the elastic modulus When the elastic modulus is less than 0.05%, the elastic modulus is easily refracted when bent in a U shape as compared with the elastic modulus being in the above range, and the elastic modulus is 0.09%. If it exceeds, the elastic modulus is in the above range, which makes it difficult to sew.
  • the artificial blood vessel 10 preferably has an anastomosis holding strength of 4.9 N or more, more preferably 4.9 to 6.5 N.
  • the anastomosis holding strength refers to a sample P (tubular artificial blood vessel) having a longitudinal length of 2 cm so that the longitudinal direction is vertical.
  • the anastomosis thread Q (surgical thread) is anastomosed at 2 mm from the end of the sample P to form an anastomosis part P1, and 2 cm away from the anastomosis part P1 of the anastomosis thread P1 is separated from the anastomosis part P1.
  • anastomosis holding strength is less than 4.9 N, the anastomosis holding strength may be broken during the anastomosis as compared with the case where the anastomosis holding strength is within the above range.
  • the artificial blood vessel 10 preferably has a porosity of 66 to 77%.
  • the porosity means the proportion of the pore portion (void portion) in the total volume.
  • V1 the amount of the pore portion in the total volume.
  • V2 the amount of the pore portion in the total volume.
  • V3 the amount of the hexane
  • the porosity is less than 66%, there is a possibility that the endothelial cells may be insufficiently fixed as compared with the case where the porosity is within the above range.
  • the porosity exceeds 78%, the porosity There is a possibility that the strength becomes insufficient as compared with the case where is in the above range.
  • the artificial blood vessel 10 preferably has a circumferential strength of 30N or more, more preferably 30 to 48N.
  • the circumferential axis strength refers to two bars B1 and B2 (for example, hexagons) inside a sample P having a longitudinal length of 5 mm. Wrench or the like) is inserted, and the rods B1 and B2 are calculated from the strength at the time of breakage when they are pulled in the opposite direction to each other with the working cell 100N or 1 kN at a measurement speed of 2 mm / min.
  • the circumferential strength is less than 30 N, the circumferential strength is more easily broken compared to the case where the circumferential strength is within the above range.
  • the artificial blood vessel 10 is preferably stored in a bag filled with pure water in order to maintain the moisture content.
  • the transplantation of the artificial blood vessel 10 is performed in a state where the moisture content is maintained.
  • the artificial blood vessel 10 can be a large-diameter artificial blood vessel or a small-diameter artificial blood vessel having an inner diameter of less than 6 mm. It can be used not only as an artificial blood vessel but also as a substitute for an artificial trachea, a stent graft, and other biological tubular structures.
  • FIG. 6 is a flowchart showing a method for manufacturing an artificial blood vessel according to the present embodiment.
  • the artificial blood vessel 10 is produced by scouring raw silk composed of silk thread to obtain silk fibroin fiber in which silk sericin partially remains on the surface of silk fibroin, and silk fibroin.
  • the artificial blood vessel 10 is obtained, so that it can be maintained for a long time.
  • the scouring step S1 is a step of scouring raw silk composed of silk thread to form silk fibroin fibers in which part of the silk sericin remains on the surface of the silk fibroin.
  • the silk thread is a thread that the silk thread discharges from the spout, and has a core-sheath structure in which a pair of silk fibroin is covered with silk sericin.
  • a silk fibroin fiber in which part of the surface silk sericin remains is obtained from the silk thread.
  • the weight of silk sericin remaining is preferably 20 to 40% of the total weight from the viewpoint of protecting silk fibroin.
  • the scouring method is not particularly limited, but it is preferable to use an enzyme.
  • enzymes include proteases.
  • the yarn making step S2 is a step in which a plurality of silk fibroin fibers are combined to form a silk fibroin fiber bundle.
  • the silk fibroin fiber is subjected to a lower twist of 1100 t / m by left twist. Then, at least two silk fibroin fibers subjected to a lower twist are combined, and an upper twist of 900 t / m is applied by a right twist. As a result, a so-called twisted silk fibroin fiber bundle is obtained.
  • the above twisting range is preferably 900 t / m to 1200 t / m for the lower twist and 700 t / m to 1000 t / m for the upper twist.
  • the knitting step S3 is a step in which the silk fibroin fiber bundle is knitted into a tubular shape by double raschel knitting to form a tubular body.
  • double raschel knitting means a knitting method in which elastic fibers are knitted in a columnar shape by a double raschel machine.
  • FIG. 7 is a partial explanatory view showing the positional relationship between the ridges, needles, and knitting yarns of the double raschel machine.
  • a silk fibroin fiber bundle is used as a knitting yarn Y (Y1 to Y6), and a tubular body is knitted by a double raschel machine R (28 gauge) of 6 sheets.
  • the gauge is the number of needles N existing between 1 inch (2.54 cm).
  • FIG. 8 is an enlarged structural diagram showing a double denby structure in double raschel knitting.
  • a double denby structure B (knitting 1-0 / 1-2 with oscillating L1 and 1-2 / 1-0 with oscillating L3) is adopted.
  • the double denby structure B is obtained by simultaneously knitting two denby structures D.
  • the knitting yarns Y1 and Y3 are controlled by the ribs L1 and L3, and the front knitted fabric K1 of the double denby structure B is knitted by the front needle FN. Then, the knitting yarns Y4 and Y6 are controlled by the loops L4 and L6, and the back knitted fabric K2 of the double denby structure B is knitted by the back needle BN.
  • a tubular tubular body W is formed by connecting the knitted fabrics K1 and K2 of the two double denby structures B knitted in this way by knitting yarns Y2 and Y5 controlled by the loops L2 and L5. In the case of this double denby structure B, since the knitting yarn is swung from needle to needle during knitting, the above-described twisting effect and covering effect can be further exhibited.
  • the removal step S4 is a step of removing the silk sericin remaining in the tubular body to form the base 1. That is, in the removal step S4, the sericin adhered in the manufacturing process of the tubular body is completely removed.
  • the removal method is not particularly limited, and a known method can be used.
  • a mixed aqueous solution of Marcel soap and sodium carbonate is heated to 100 ° C., a tubular body is added, boiled and washed with stirring for several hours, then boiled and washed together in the order of sodium carbonate aqueous solution and distilled water, and dried. By doing so, the base 1 from which sericin has been removed is obtained. These boiling washings may be repeated a plurality of times.
  • a sponge-like covering portion 2 covered with silk fibroin on the surface of the base portion is formed so that the thickness H1 of the covering portion 2 on the front side portion of the base portion is 0.8 mm or more to form a temporary artificial blood vessel. It is a process. Note that the thickness H1 of the covering portion 2 is the same as described above, and a description thereof will be omitted.
  • the coating step S5 is performed by immersing the base 1 in a silk fibroin solution, attaching silk fibroin to the back and front surfaces of the base 1, and freeze-drying.
  • the silk fibroin solution is obtained by removing silk sericin, then dissolving the silk fibroin fiber, sponge, and film in a neutral salt such as lithium bromide or calcium chloride, and then removing the neutral salt by dialysis. .
  • the coating step S5 is performed by coating the base 1 with a mixed solution of a hole source and silk fibroin. At this time, the liquid mixture passes through the stitches of the base 1 and reaches the surface on the back side of the base 1. Thereafter, if the pore source material is removed by freezing and then sufficiently immersed in water, the coating portion becomes a silk sponge.
  • the hole source material include polyglycols.
  • the silk fibroin solution in both steps may further contain an antithrombotic agent such as heparin.
  • the base 1 that has undergone the coating step S5 may be subjected to autoclave sterilization at 120 ° C. for 20 minutes.
  • a sponge-like (porous) covering portion 2 is formed on the surface of the base portion 1.
  • the immersing step S6 is a step of immersing the temporary artificial blood vessel in pure water in a state where the wet state of the temporary artificial blood vessel is maintained after the coating step S5. After the coating step S5, in order to maintain the wet state of the temporary artificial blood vessel, the strain generated when the moisture content of the temporary artificial blood vessel is temporarily reduced (for example, less than 60%) by performing the immersion step S6 promptly. Generation of cracks can be suppressed.
  • the dipping step S6 is performed, for example, by dipping in a bag filled with pure water.
  • the period of immersion in pure water is not particularly limited, but is preferably 1 hour or longer, and more preferably 1 hour to 1 week. If the immersion period is less than 1 hour, the moisture content may not be sufficient as compared to the case where the immersion period is within the above range. If the immersion period exceeds 1 week, There is a risk that the silk sponge on the surface of the artificial blood vessel may be removed or hardened as compared with the case where the period of time is within the above range.
  • the dipping step S6 is performed until just before the transplantation of the artificial blood vessel 10.
  • the artificial blood vessel 10 can be transplanted in a state where generation of strain and cracks is suppressed as much as possible.
  • the artificial blood vessel 10 having the water content described above is obtained.
  • the silk fibroin fiber is subjected to a lower twist
  • the silk fibroin fiber bundle formed by combining a plurality of silk fibroin fibers is subjected to an upper twist, but is not necessarily essential. It is not a configuration.
  • the artificial blood vessel 10 according to the present embodiment can be subjected to bellows processing or the like in order to improve flexibility. Moreover, in order to maintain a moist state, you may further coat with glycerin.
  • FIG. 8 shows a double denby structure in double raschel knitting.
  • the present invention is not limited to this, and a denby structure, an inverted half structure, or the like may be used.
  • the reverse half structure H (knitted 1-2 / 1-0 with oscillating L4 and 1-0 / 2-3 with oscillating L6) shown in FIG. 9 is formed of Denby structure D and chord structure C.
  • the sinker loop S1 of the cord tissue C is longer than the double denby tissue B by one stitch compared to the sinker loop S2 of the Denby tissue D, and thus a dense knitted fabric is obtained and used as the tubular body W. In some cases, it is effective in preventing blood leakage.
  • this reverse half structure H since the way of knitting yarn to the needle during knitting becomes larger than that of the Denby structure, a twisting effect and a covering effect are further exhibited.
  • Examples 1 and 2 and Comparative Examples 1 and 2 First, raw silk composed of silk thread and protease ("Esperase” (trade name); manufactured by Novozymes Japan Co., Ltd.) are added to water and scoured under mild conditions, and silk sericin is formed on the surface of silk fibroin. Part of the remaining silk fibroin fiber was obtained (scouring process). At this time, the weight of the remaining silk sericin was 10 to 15% of the total weight.
  • the silk fibroin fiber After washing and drying, the silk fibroin fiber is subjected to a lower twist of 1100 t / m by left twist, and 30 silk fibroin fibers are combined to form a silk fibroin fiber bundle, and further, an upper twist of 900 t / m is twisted by right twist.
  • the silk fibroin fiber bundle was obtained by applying (spinning process).
  • the silk fibroin fiber bundle was knitted into a tubular shape by double raschel knitting according to the double denby structure shown in FIG. 8 to obtain a tubular body (knitting step).
  • the tubular body is put into a mixed aqueous solution of 12 w / v% Marcel soap and 8 w / v% sodium carbonate heated to 95 ° C., boiled for 120 minutes, and then boiled for 10 minutes with 2 w / v% sodium carbonate aqueous solution. Then, the base 1 from which silk sericin remaining in the tubular body was removed was obtained by performing the operation of washing in distilled water heated to 95 ° C. three times and the operation of washing with warm water three times (removal step). ).
  • silk fibroin solution is dissolved in 9 mol of neutral salt aqueous solution (lithium bromide, lithium chloride, calcium chloride or lithium thiocyanate), and then neutral salt is removed by dialysis.
  • the base 1 was immersed in a silk fibroin solution at a concentration of 4 w / v% for 30 minutes under normal pressure, and the silk fibroin was adhered to the back side and front surface of the base 1 and left at ⁇ 20 ° C. for 1 hour. After putting it in a freeze dryer overnight, it was put in a pouch together with water, sterilized by an autoclave, and stored in distilled water to obtain a temporary artificial blood vessel in which the covering portion 2 was formed (coating step).
  • neutral salt aqueous solution lithium bromide, lithium chloride, calcium chloride or lithium thiocyanate
  • the temporary artificial blood vessel was immediately immersed in pure water. By adjusting the immersion time, a sample having a diameter of 3.5 mm was obtained (immersion step). Table 1 shows the physical property data of the obtained sample.
  • Example 3 instead of the coating process described above, the base 1 is immersed for 10 minutes under normal pressure in a coating solution in which polyethylene glycol diglycidyl ether is mixed at a weight ratio of 1: 1 with a 4 w / v% silk fibroin aqueous solution. Silk fibroin was attached to the back side and front side surfaces of the base 1 and left at ⁇ 20 ° C. overnight. After thawing at room temperature, a sample having a diameter of 3.5 mm was obtained in the same manner as in Example 1 except that the coating part 2 was formed by immersing in water for 3 days to remove polyethylene glycol diglycidyl ether. Table 1 shows the physical property data of the obtained sample.
  • Example 3 A sample having a diameter of 3.5 mm was obtained in the same manner as in Example 1 except that the dipping process was not performed. Table 1 shows the physical property data of the obtained sample.
  • Example 4 In the same manner as in Example 1, except that raw silk having the same composition in which carbons of 13 amino acids such as Ala, Tyr, Gly, and Ser were marked with hydrogen and deuterium was used instead of raw silk, A 5 mm sample was obtained. The marking was performed by mixing [3- 13 C] Tyr and [3- 13 C] Ser in an artificial feed and orally administering it to a rabbit at the age of 5 years.
  • Example 4 A sample with a diameter of 3.5 mm was obtained in the same manner as in Example 4 except that the dipping process was not performed.
  • the artificial blood vessel according to the present embodiment can be maintained for a long period of time.
  • the artificial blood vessel of the present invention is used for a purpose of temporarily securing a blood flow path during surgery or a use as a substitute blood vessel for a diseased blood vessel.
  • the artificial blood vessel of the present invention can be a large-diameter artificial blood vessel or a small-diameter artificial blood vessel having an inner diameter of less than 6 mm. According to the artificial blood vessel of the present invention, it becomes possible to make it open for a long time.

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  • Health & Medical Sciences (AREA)
  • Transplantation (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
PCT/JP2013/003078 2012-05-14 2013-05-14 Vaisseau sanguin artificiel, et procédé de fabrication de celui-ci Ceased WO2013172021A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
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JP2014014697A (ja) * 2008-11-14 2014-01-30 Tokyo Univ Of Agriculture & Technology 人工血管の製造方法
JP2015214132A (ja) * 2014-04-21 2015-12-03 日立化成株式会社 フィブロイン複合体
JP2017000321A (ja) * 2015-06-08 2017-01-05 日本毛織株式会社 人工血管用組紐
CN112043875A (zh) * 2020-08-06 2020-12-08 苏州大学 一种原位内膜再生的血管支架覆膜及其制备方法
JP2023098873A (ja) * 2021-12-29 2023-07-11 鉄隆 西山 医療用の環状構造物の製造方法、医療用の環状構造物の製造方法で使用する芯材及び医療用の環状構造物

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Publication number Priority date Publication date Assignee Title
JPH05237140A (ja) * 1991-02-27 1993-09-17 Seiren Co Ltd 人工血管およびその製造方法
JPH1199163A (ja) * 1997-09-29 1999-04-13 Terumo Corp 血管補綴材
JP2008073408A (ja) * 2006-09-25 2008-04-03 Japan Science & Technology Agency フィブロイン糸を使用した小動脈用人工血管
JP2010137041A (ja) * 2008-11-14 2010-06-24 Tokyo Univ Of Agriculture & Technology 人工血管の製造方法
WO2012090553A1 (fr) * 2010-12-28 2012-07-05 国立大学法人東京農工大学 Procédé de fabrication de vaisseau sanguin artificiel
WO2012111309A1 (fr) * 2011-02-18 2012-08-23 福井経編興業株式会社 Tube double raschel tricoté pour vaisseaux sanguins synthétiques et son procédé de production

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05237140A (ja) * 1991-02-27 1993-09-17 Seiren Co Ltd 人工血管およびその製造方法
JPH1199163A (ja) * 1997-09-29 1999-04-13 Terumo Corp 血管補綴材
JP2008073408A (ja) * 2006-09-25 2008-04-03 Japan Science & Technology Agency フィブロイン糸を使用した小動脈用人工血管
JP2010137041A (ja) * 2008-11-14 2010-06-24 Tokyo Univ Of Agriculture & Technology 人工血管の製造方法
WO2012090553A1 (fr) * 2010-12-28 2012-07-05 国立大学法人東京農工大学 Procédé de fabrication de vaisseau sanguin artificiel
WO2012111309A1 (fr) * 2011-02-18 2012-08-23 福井経編興業株式会社 Tube double raschel tricoté pour vaisseaux sanguins synthétiques et son procédé de production

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014014697A (ja) * 2008-11-14 2014-01-30 Tokyo Univ Of Agriculture & Technology 人工血管の製造方法
JP2015214132A (ja) * 2014-04-21 2015-12-03 日立化成株式会社 フィブロイン複合体
JP2017000321A (ja) * 2015-06-08 2017-01-05 日本毛織株式会社 人工血管用組紐
CN112043875A (zh) * 2020-08-06 2020-12-08 苏州大学 一种原位内膜再生的血管支架覆膜及其制备方法
JP2023098873A (ja) * 2021-12-29 2023-07-11 鉄隆 西山 医療用の環状構造物の製造方法、医療用の環状構造物の製造方法で使用する芯材及び医療用の環状構造物
JP7407904B2 (ja) 2021-12-29 2024-01-04 鉄隆 西山 医療用の管状構造物の製造方法、医療用の管状構造物の製造方法で使用する芯材及び医療用の管状構造物

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