JP6487783B2 - Artificial blood braid - Google Patents

Description

  The present invention relates to an artificial blood vessel material. More specifically, the present invention relates to a braid for an artificial blood vessel that has a high yarn density and is suitable for a small-diameter artificial blood vessel.

  Polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) used for large-diameter artificial blood vessels have a problem that they tend to block after transplantation when applied to small-diameter artificial blood vessels having an inner diameter (hollow diameter) of 6 mm or less. . This is said to be due to thickening of the intima due to incompatibility of the vascular material and occlusion due to thrombus formation. Therefore, at present, autologous vein transplantation is performed for bypass to the knee joint periphery, etc., but there are many patients who do not have compatible blood vessels and cannot perform autologous vein transplantation because of heavy burden on the patient. There are many problems. In recent years, with the aging of patients and the increase in diabetes, the demand for regenerative treatment of small blood vessels is increasing. Therefore, development of an artificial blood vessel having antithrombotic properties that can be used particularly for small-diameter blood vessels such as peripheral blood vessels has been desired.

  On the other hand, silk thread has high biocompatibility, is thin, strong, has moderate elasticity and flexibility, has good sliding properties, and is easy to tie and hard to fray. It is a natural fiber used as Various regenerated silk materials that utilize the high biocompatibility of silk have been developed so far, and are expected to be used in a wide range of fields such as medicine, biochemistry, food, and cosmetics. In particular, it is attracting attention as a material for regenerative medicine. As an attempt to produce an artificial blood vessel using silk, braided structures have been proposed (Patent Documents 1 to 3).

JP 2004-173772 A JP 2009-279214 A JP 2014-050412 A

  However, the prior art as described above has not been optimized in the fineness of the braid, the yarn angle, the number of braids, and the like, and further improvement has been demanded particularly regarding the strength necessary for transplantation.

  In order to solve the above-mentioned conventional problems, the present invention provides a braid for an artificial blood vessel that is suitable for a small-diameter artificial blood vessel having a high yarn density and excellent strength by optimizing the fineness, yarn angle, the number of times of braiding, etc. To do.

  The braid for artificial blood vessels of the present invention is a braid for artificial blood vessels in which a biocompatible fiber yarn is made into a braid, and the single yarn fineness of the braid constituting the braid is in a range of 117 to 932 dtex, and the braid Is a braid of 24 or more punches, and the braid angle forming the braid is arranged at a predetermined angle in the range of 35 to 45 ° with respect to the circumferential direction, and the number of braids per inch is 25 or more It is characterized by having a cylindrical shape as a whole.

  The braid for artificial blood vessels of the present invention is a braid for artificial blood vessels in which a biocompatible fiber yarn is made into a braid, and the fineness of the single yarn constituting the braid is in the range of 117 to 932 dtex, and the braid Is a braid of 24 or more punches, and the braid angle forming the braid is arranged at a predetermined angle in the range of 35 to 45 ° with respect to the circumferential direction, and the number of braids per inch is 25 or more In addition, since the overall shape is cylindrical, the braided cord for artificial blood vessels suitable for small-diameter artificial blood vessels can be provided. Furthermore, the braid for artificial blood vessels of the present invention has strength that does not rupture with blood pressure and elasticity equivalent to that of a blood vessel in a living body.

FIG. 1 is a side view of a trace obtained by observing an artificial blood braid according to an embodiment of the present invention with an optical microscope (magnification 10 times). FIG. 2 is a schematic perspective view of the braid. FIG. 3A is a schematic explanatory view showing the braid manufacturing apparatus, and FIG. 3B is an operation diagram showing the movement of the bobbin. FIGS. 4A and 4B are schematic explanatory diagrams of a measuring device for measuring the peripheral axis breaking strength and the peripheral axis breaking elongation (strain) of the braid for artificial blood vessels in one embodiment of the present invention. FIG. 5 is a photograph showing a state in which the flaw-prevented artificial blood vessel braid according to another embodiment of the present invention does not fray and the hole does not widen even if it is strongly pulled with a wire. FIG. 6A is a photograph showing an end portion of the braid for artificial blood vessels in which fraying is prevented according to the same embodiment, and FIG.

  As a result of examining the fineness of the braided single yarn, the number of braids to be launched, and the angle of the braided yarn, the present inventors found that the yarn density and stitch density are high and strong within the scope of the present invention. The present inventors have found that an artificial blood braid suitable for a caliber artificial blood vessel can be obtained.

  The braid for artificial blood vessels of the present invention is a braid for artificial blood vessels in which a biocompatible fiber yarn is made into a braid. When it is a braid, it is easy to form in a cylindrical shape. Biocompatible fiber yarns are silk yarn, polylactic acid yarn, pocaprolactone, polyglycolic acid and the like, and their own safety is known for surgical yarns and the like. The useful life in the human body is said to be several years for silk, about 6 months for polylactic acid, 1 to 2 years for polycaprolactone, and about 2 weeks for polyglycol.

  The fineness of the single braid constituting the braid of the present invention is in the range of 117 to 932 dtex, preferably 117 to 700 dtex, and more preferably 117 to 467 dtex. If it is the said range, it can be set as the braid for artificial blood vessels suitable for a small diameter artificial blood vessel.

The braid number is 24 or more. Preferably 24-64 beating, even more preferably braids beating 32 to 64. Thereby, the stitch density can be increased. The angle of the braid constituting the braid is adjusted to a predetermined angle in the range of 35 to 45 ° with respect to the circumferential direction. A preferred angle is 37-45 °. If the angle of the braid is within the above range, there is no distortion and a braid arranged in a cylindrical shape can be obtained. The number of sets is 25 / inch or more, preferably 25 to 54 / inch. Thereby, the yarn density and the stitch density are high and the strength is high, and the elasticity is equivalent to that of a living blood vessel .

  The braided yarn may be a multifilament yarn or a spun yarn. The multifilament yarn may be raw yarn or processed yarn. These yarns can also be used as a mixture.

  The braid of the present invention preferably has a hollow diameter (inner diameter) of 1 to 6 mm, more preferably 2 to 5 mm. Such braided artificial blood vessels can be formed with braids.

  The braid has a length of preferably 10 to 50 mm, more preferably 10 to 40 mm. Within this range, it is convenient for transplanting in vivo.

  The braid preferably has a wall thickness of 0.32 to 1.20 mm. Within this range, the strength is high, and even when stress is applied, the hollow space can be maintained and sufficient strength as an artificial blood vessel can be maintained.

  The braid may be prevented from fraying. Fraying prevention is performed by incorporating a heat-fusible biocompatible fiber yarn into the braid and bonding or heat-sealing the ends. When the braid is a silk thread, a polylactic acid thread may be sewn and bonded to the end of the braid, and fraying prevention treatment is preferably performed by welding or melting. Polylactic acid is thermoplastic and melts at 180-195 ° C. When bonding, add chloroform to the ends and dissolve. In the case of a braid of polylactic acid yarn, pocaprolactone, and polyglycolic acid, a fraying prevention treatment can be performed by bonding or melting the end of itself. It is preferable to use a copolymer such as polylactic acid yarn, pocaprolactone, polyglycolic acid and the like, and bond or heat-seal at a temperature of 100 ° C. or less without deteriorating the silk.

  It is preferable that the braid has a hollow diameter of 3.5 mm and a length of 10 mm and has a circumferential breaking strength of 1 N or more. The above strength is practically sufficient. It is preferable that the peripheral axis breaking elongation (strain) is 79 to 175% with a hollow diameter of 3.5 mm and a length of 10 mm. If it is the said elongation, it can be used as a braid for artificial blood vessels.

  The braid of the present invention is preferably a braid assembled with 24 or more braids. A preferable number of hits is 24 to 64. 24, 32, 40, 48, 56, 64, 72, 80, 88, 96 can be adopted as the number of strikes of the assembling machine (the number of bobbins set up when assembling the braid). The number of strokes 24 can produce an inner diameter of 1 to 3 mm, the number of strokes 32 can produce an inner diameter of 2 to 4 mm, and the number of strokes 64 can produce a diameter of about 3 to 6 mm. The braid includes round punching and square punching, but the braid assembled by round punching is hollow and suitable for a braid for an artificial blood vessel.

  The string making machine can mainly change the thickness (inner diameter, outer diameter) of the braid depending on the number of hits. When assembling in the string making process, the string is moved vertically in the center of the string making machine by moving a round or polygonal metal or wooden rod with a rounded end whose tip is roughly equivalent to the inner diameter of the string in the vertical direction. However, a cylindrical braid can be obtained by assembling (pushing up).

  When the tension is lowered during the string making process, a braid with good coverage and clogged with the stitches is obtained. When it is pulled with tension applied, care must be taken because the braid is stretched, the inner diameter becomes thinner, and the stitches may be displaced in some cases. In addition, when the single yarn fineness is larger than that of the present invention, the yarn becomes hard, so that there is a tendency that the stitches are not sufficiently clogged even in the pushing-up operation and a void portion is easily formed. Further, the shape can be stabilized by installing a heater in a stage from pushing up to taking-out and performing non-contact heat treatment.

  When the artificial blood braid is used as it is as an artificial blood vessel as it is, blood leaks. Therefore, it is preferable to perform a coating treatment with a material having biocompatibility. Biocompatible materials include silk fibroin, bio-absorbable polymers such as poly-L lactic acid, polycaprolactone, and polyglycolic acid, and copolymers thereof. Silk fibroin aqueous solution, poly-L lactic acid, polycaprolactone Polyglycolic acid can be coated by dissolving in an organic solvent such as acetic acid, immersing the braid in the resulting solution, and freeze-drying at −30 ° C. For coating, the obtained nanofiber can be coated on the braid by electrospinning the above solution.

  This will be described below with reference to the drawings. FIG. 1 is a trace drawing of the side surface of an artificial blood vessel braid in one embodiment of the present invention observed with an optical microscope (magnification 10 times). The braid 1 is assembled with the braids 2 and 3, but no opening (gap) is observed on the surface thereof. No gaps are seen when the stitches of the braids are tightly packed. The braids 2, 3 are arranged at a predetermined angle in the range of 35-45 ° with respect to the circumferential method. The angle Θ in the lower right of FIG. 1 is the assembly angle. FIG. 2 is a schematic perspective view of a braid in one embodiment of the present invention. The braid 4 has a cylindrical shape as a whole, the cylindrical portion is composed of the braided yarn 5, and both ends are fraying prevention processing portions 6a and 6b. In this state, it becomes a braid for artificial blood vessels.

  FIG. 3A is a schematic explanatory view showing an apparatus for manufacturing a round braid used in one embodiment of the present invention, and FIG. 3B is an operation diagram showing the movement of the bobbin. The manufacturing apparatus 10 includes a gantry 11, a bobbin (carrier) 12, a mandrel 14, and a driving device (not shown). As the bobbin 12 rotates on the solid line of the track 19 on the gantry 11, the yarn 13 wound around the bobbin 12 is braided on the mandrel 14 that pushes up to create a braid. The push-up portion 16 includes a hemispherical head that moves up and down in conjunction with the rotational movement of the bobbin 12 and a cylindrical (or polygonal) cylindrical portion 15 at the center thereof. The outer diameter of the cylindrical portion 15 is substantially equal to the inner diameter of the braid 17. If necessary, the braid 17 is sent to a heater and heat set. The braid 17 passes through the take-out guide (pulley) 18 and is shaken off by the storage container. In the above, the mandrel 14 stroke length and the number of strokes are set as appropriate. Heat set is not essential for silk braids, but heat set is effective for braids using yarns made of thermoplastic resin.

  EXAMPLES Hereinafter, although this invention is demonstrated further more concretely using an Example and a comparative example, this invention is not limited to a following example. Various measurements in the following Examples and Comparative Examples were performed as follows.

<Inner diameter, thickness (wall thickness), number of groups>
Inner diameter: Conical taper gauge (Measuring instrument: Niigata Seiki Taper Gauge 710B type (4-15mm) with the tip of the taper facing up, insert the braid and put it lightly, read the gauge on the braid end face Braid (eyes / inch): A magnifying glass (linen tester) having a frame of 1 inch on each side is lightly brought into contact with the side of the braid so that the braid does not deform, and the braid between 1 inch (25.4 mm) The number was measured to 0.5.Thickness (thickness): Using a caliper, it was sandwiched between the inside and outside of the braid, and the thickness (mm) was measured.
<Weight per 10mm braid (g / 10mm)>
A braid that was allowed to stand for 24 hours in a standard state (temperature 20 ± 3 ° C., relative humidity 65 ± 3%) was cut into a predetermined length. The weight was measured and the weight per 10 mm was computed.
<Braid angle>
The side surface of the braid was observed with an optical microscope (magnification 10 times), and the angle of the braid with respect to the circumferential direction (X direction in FIG. 1) was measured. The angle of the braid was measured a total of 10 times and made the average value.
<Circumferential fracture strength and circumferential elongation at break (strain)>
An L-shaped jig is sandwiched between the top and bottom of a tensile tester (EZ-graph (manufactured by SHIMAZU)), through an artificial blood vessel cut to a length of 10 mm, and a peripheral axis under the conditions of a load cell 100N and a tensile speed of 2 mm / min. The tensile strength in the direction of the peripheral axis was calculated from the breaking strength and displacement of the artificial blood vessel. FIGS. 4A and 4B are schematic explanatory diagrams of a measuring device for measuring the peripheral axis breaking strength and the peripheral axis breaking elongation (strain) of the braid for artificial blood vessels in one embodiment of the present invention. L-shaped jigs 23 and 24 are fixed to the upper and lower load cells 21 and 22, respectively, and a braid 25 is attached. The arrow in FIG. 4A shows a state in which the wrinkle is not pulled. From this state, the upper and lower load cells 21 and 22 are pulled apart as shown in FIG. 4B, and the braid 25 is pulled in parallel by the L-shaped jigs 23 and 24. Thus, the circumferential axis breaking strength and the circumferential axis breaking elongation (strain) are measured.
<Coating properties>
The side of the braid was observed with an optical microscope (magnification 10 times) and judged as follows.
A There is no gap B B There is a gap between the yarns C The braid-constituting yarn arrangement is disordered, and the gaps between the yarns are also large.
Hold the braid with your thumb and forefinger, compress it several times, repeat the recovery operation, and evaluate the presence / absence of elasticity based on the shape retention / recovery and followability (familiarity). Good B Recoverability is low, somewhat hard and inadequate, and lacks elasticity C Crushes due to lack of elasticity

Example 1
Ten silk filament yarns (fineness: 23.3 decitex) were twisted as a braid. The twist was 40 / m and the twist direction was S, and it was wound on a bobbin. A braid having an inner diameter of 1.5 mm was manufactured by round punching 24 times using the braid manufacturing apparatus 30 shown in FIG. The characteristics of the braid obtained are summarized in Table 1.

(Examples 2-10, Comparative Examples 1-2)
The same procedure as in Example 1 was performed except that the fineness, the number of braids, and the inner diameter of the silk filament yarn were shown in Table 1. The above conditions and results are summarized in Table 1.

  As is apparent from Table 1, Examples 1 to 10 have high yarn density and strength, strength that does not rupture with blood pressure, elasticity equivalent to that of living blood vessels, and a braid for artificial blood vessels that is suitable for small-diameter artificial blood vessels. We were able to.

  On the other hand, in Comparative Examples 1 and 2, since the braid angle or the number of braids was low, the circumferential fracture strength was not preferable.

(Example 11)
A single piece of polylactic acid (PLLA) and a diameter of 0.0075 mm as a bioabsorbable yarn is drawn to five silk yarns having a fineness of 23.3 decitex of Example 9 to produce a braid, and chloroform is attached to the ends. Bonding was performed at 25 ° C. for 10 seconds. As a result, it was possible to produce a braid having elasticity without being frayed even when a suture needle was applied to the end portion of less than 1 mm. The photograph of FIG. 5 is a photograph showing a state in which the fraying-prevented braid for artificial blood vessel according to this embodiment does not fray even if it is strongly pulled with a wire and the hole does not expand. FIG. 6A is a photograph showing an end portion of a braid for artificial blood vessels in which fraying is prevented in this embodiment, and FIG.

  The braid for artificial blood vessels of the present invention is suitable as a material for artificial blood vessels of animals such as human bodies, pets and livestock.

DESCRIPTION OF SYMBOLS 1,4 Artificial blood vessel braid 2,3,5 Braid 6a, 6b End fray processing part 30 Braid manufacturing apparatus 11 Base 12 Bobbin 13 Thread 14 Mandrel 15 Cylindrical part 16 Raised part 17 Braid 18 Takeout guide (pulley)
19 Track θ Assembly angle 21, 22 Load cell 23, 24 L-shaped jig 25 Braid

Claims (10)

A braid for artificial blood vessels in which a biocompatible fiber yarn is made into a braid,
The single yarn fineness of the braid constituting the braid is in the range of 117 to 932 dtex,
The braids are braids of 24 or more strikes, and the braids constituting the braids are arranged at a predetermined angle in a range of 35 to 45 ° with respect to the circumferential direction, and the number of stitches per inch A braid for artificial blood vessels, which is 25 or more and has a cylindrical shape as a whole.   The braid for artificial blood vessels according to claim 1, wherein the braid has a hollow diameter of 1 to 6 mm.   The braid for artificial blood vessels according to claim 1 or 2, wherein the braid has a length of 10 to 50 mm.   The braid for artificial blood vessels according to any one of claims 1 to 3, wherein the braid has a thickness of 0.32 to 1.20 mm.   5. The braid for artificial blood vessels according to claim 1, wherein the biocompatible fiber yarn is at least one selected from silk yarn, polylactic acid yarn, polycaprolactone, and polyglycolic acid.   The braid for artificial blood vessels according to any one of claims 1 to 5, wherein an end portion of the braid is prevented from fraying.   7. The braid for artificial blood vessels according to claim 6, wherein the fraying prevention is formed by incorporating a heat-fusible biocompatible fiber yarn into the braid and bonding or heat-sealing the ends.   The braided cord for artificial blood vessels according to any one of claims 1 to 7, wherein the braided cord has a hollow diameter of 3.5 mm and a length of 10 mm, and a peripheral axis breaking strength is 1 N or more.   The braided cord for artificial blood vessels according to any one of claims 1 to 8, wherein the braided cord has a hollow diameter of 3.5 mm and a length of 10 mm, and has a circumferential fracture elongation (strain) of 79 to 175%.   The braid for artificial blood vessels according to any one of claims 1 to 9, wherein the braid is round-punched.