JP6154622B2 - Porous tube with core material and method for producing the same - Google Patents

Description

The present invention relates to a cored porous tube manufactured by an electrospinning method and a method for manufacturing the same .

  In the electrospinning method, by applying a high voltage with a potential difference between the injection hole (syringe needle, nozzle, etc.) of the polymer solution and the collector, the injection state of the polymer solution from the injection hole to the collector (on the collector side) In this process, the solution component is instantly evaporated during the injection process, and the polymer is shaped into ultrafine fibers and further stretched into nanofibers. It refers to a method of producing a molded body (a structure in which nanofibers are intertwined and a continuous vent is formed like a non-woven fabric, and can also be referred to as a “nonwoven fabric molded body”). The produced porous molded body can be suitably used as a high-density filter, a scaffold for regenerative medicine, and the like.

  In this electrospinning method, it has been proposed to use a cylindrical or cylindrical or rod-shaped collector as the collector, thereby making the porous molded body cylindrical or tubular (for example, Patent Documents). (See 1 and 2 etc.). By adopting such a shape, the porous molded body can be used as an artificial blood vessel.

Japanese Patent No. 4904083 Japanese Examined Patent Publication No. 62-61703

  In order to use the porous molded body produced by the electrospinning method in the field of regenerative medicine, it is necessary to perform sterilization (for example, autoclave sterilization) in advance. By performing this sterilization treatment, the porous molded body tends to shrink. In the case where the porous molded body is formed into a tubular shape, the pipe diameter (inner diameter and outer diameter) is reduced at once, the wall thickness is decreased, and the length is increased immediately after the porous molded body is taken out from the collector immediately after production. Will be shortened. Therefore, in some cases, there is a possibility that it may lead to a serious problem in quality (external accuracy).

On the other hand, the porous molded body is in a soft state in which flexibility and stretchability are allowed to some extent. However, in other words, if the porous molded body is not handled well, there is a possibility that creases, crushing deformation, etc. will occur relatively easily. Also, once the porous molded body is broken or crushed, it cannot be restored to its original shape, so it becomes unusable and must be discarded. For these reasons, when the porous molded body is formed into a tubular shape, bulky strict packaging and packaging are required to prevent deformation, and there is a problem that the distribution cost increases.

  When the porous molded body is formed into a tubular shape and used as an artificial blood vessel or the like, the required length varies depending on the treatment site and is not always constant. However, in general, a porous molded body produced for an artificial blood vessel is set to a fixed size (for example, 100 to 300 mm), and is distributed as a sterilized package in units of this fixed size. It has become. Therefore, the problem that cut loss (cutting and discarding useless length) often occurs has been pointed out.

The present invention has been made in view of the above circumstances, and is capable of causing shrinkage that may occur after production in a tubular molded body (hereinafter referred to as “porous tube material”) produced by an electrospinning method. A porous tube material with a core material and a method for manufacturing the same that can maintain high quality by suppressing as much as possible, achieve reduction of distribution cost by preventing creases and crushing deformation, and solve the problem of cut loss The purpose is to provide.

In order to achieve the above object, the present invention has taken the following measures.
That is, the porous tube material with a core material according to the present invention satisfies a porous tube material having a tubular shape in which a tube wall is formed by an accumulation layer of nanofibers, and a hollow portion surrounded by the tube wall with respect to the porous tube material. The tube wall is totally backed up from the inside and has a conductive core material necessary for the collector of the electrospinning method when the tube wall is formed, and the shrinking deformation is stably terminated during the circulation of the porous tube material. It is characterized by having a packaging material or a packaging material that keeps the porous tube material in a sterilized state with the conductive core material remaining as a shape-retaining material for preventing deformation and breakage deformation .

It is preferable that a release layer that facilitates axial movement of the conductive core member is provided between the inner peripheral surface of the tube wall and the outer peripheral surface of the conductive core member.
The conductive core material is preferably formed of a flexible metal wire.
On the other hand, in the method for manufacturing a core-containing porous tube according to the present invention, the conductive core material is formed in the tube wall by forming a tube wall with an accumulation layer of nanofibers around the conductive core material by electrospinning. Forming a porous tube in a state where the hollow portion to be formed is totally backed up from the inside, sterilizing the porous tube with the conductive core material remaining in the hollow portion, and sterilizing the porous tube The porous tube material is packaged or packed together with the conductive core material.

In the cored porous tube according to the present invention and the manufacturing method thereof , shrinkage that can occur after manufacturing can be suppressed as much as possible to maintain high quality, and folding costs and deformation can be prevented, thereby reducing distribution costs. In addition, the problem of cut loss can be solved.

It is the perspective view which showed the porous tube material with a core material which concerns on this invention. It is the figure which showed typically the manufacturing apparatus of the porous tube material with a core material which concerns on this invention. It is the perspective view explaining the manufacturing method of the porous tube material with a core material which concerns on this invention.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 shows a cored porous tube 1 according to the present invention. The porous tube 1 is formed in a tubular shape having a circular cross section (ring shape) and a continuous cross section in the tube axis direction. A conductive core member 3 is inserted into a hollow portion in the tube surrounded by the tube wall 2 in a skewered manner. A release layer 4 is provided between the inner peripheral surface of the tube wall 2 and the outer peripheral surface of the conductive core member 3.

The porous tube 1 can be applied to a human artificial blood vessel. In this case, for example, the inner diameter of the hollow portion surrounded by the tube wall 2 (substantially the same as the outer diameter of the conductive core material 3). Is preferably about 0.5 mm to several mm. However, this dimension is variously changed when applied to artificial blood vessels of animals other than humans, or when the porous tube 1 is used for other purposes such as a filter, and is not limited in the present invention. Is not to be done. The same applies to the wall thickness of the tube wall 2, and the present invention is not limited in any way.

Such a tube wall 2 is formed by electrospinning, and is an integrated layer formed by integrating nanofibers generated from a polymer solution. In this way, the tube wall 2 formed by the accumulation of nanofibers has a structure in which nanofibers are entangled and a continuous vent is formed like a non-woven fabric.
Various polymers that can be used in the electrospinning method can be used as they are as the polymer used as the material for forming the tube wall 2 and the solvent thereof.

For example, as the polymer, those exemplified below can be used. That is,
[Natural Polymer] At least one selected from the group consisting of collagen, gelatin, proteoglycan, dextran, chitin, chitosan, silk, hyaluronic acid, albumin, elastin, nucleic acid, heparin and heparan sulfate, and the like.
[Synthetic Polymer] Polylactic acid, polyglycolic acid, polylactide, polyglutamic acid, poly-ε-caprolactone, poly-p-dioxane, polyα-malic acid and poly-β-hydroxybutyric acid, and polylactic acid and polycaprolactone At least one selected from the group consisting of copolymers, or polyethylene, polypropylene, polyamide, polyester, polyethylene glycol, polycarbonate, polyvinylidene fluoride, polyurethane, polystyrene, polyacrylonitrile, polytetrafluoroethylene, polyvinyl alcohol, polyethylene Group consisting of terephthalate, nylon, poly N isopropyl acrylamide, polyvinyl chloride, polymethyl methacrylate, polydimethyl siloxane, polyallyl sulfone and polysulfone Al least one selected, and so on.

  As the solvent, HFIP (1,1,1-3,3,3 hexafluoroisopropanol), DMF (N, N dimethylformamide), sulfuric acid, hydrochloric acid, formic acid, methanol, ethanol, DMSO (dimethyl sulfoxide) , THF (tetrahydrofuran), acetone, MEK (methyl ethyl ketone), toluene, cyclohexane, and the like.

  The conductive core material 3 is supposed to be able to fill the hollow portion surrounded by the tube wall 2, and in the present embodiment, the cross-sectional shape of the porous tube material 1 is annular as described above. The cross-sectional shape of the core material 3 is circular. In this way, the conductive core material 3 can back up the tube wall 2 from the inner surface side thereof (circumferential direction and tube axis direction) via the release layer 4, and thereby the shape retaining effect on the tube wall 2 can be obtained. can get. However, the peeling layer 4 can be omitted depending on circumstances, and if it is omitted, the conductive core member 3 can be in direct contact with the inner peripheral surface of the tube wall 2 and directly backed up.

The cross-sectional shape of the porous tube 1 is not limited to an annular shape in the first place, and may be an elliptical or oval annular shape or a rectangular hollow shape. Therefore, as a matter of course, the cross-sectional shape of the conductive core material 3 may be a shape corresponding to the cross-sectional shape of the porous tube material 1.
Such a conductive core material 3 can be used as a collector (electrode) when the tube wall 2 is formed by performing the electrospinning method. For example, a metal wire can be used. As the metal wire, it is preferable to adopt a flexible one. Specifically, a wire such as stainless steel, copper, aluminum, or gold may be used. In particular, by selecting gold, silver, platinum or the like having high purity, even if metal ions remain on the inner surface side of the hollow portion when the porous tube material 1 is used for an artificial blood vessel, this metal The effect of preventing the onset of metal allergy caused by ions can be expected.

When the conductive core material 3 is made conductive, the use of a metal wire is not limited. For example, a metal foil is attached to the outer peripheral surface of a non-conductive material such as a resin wire or elastic silicon or rubber, or a coating containing a metal component is applied (including deposition, vapor deposition, plating, etc.) ) To form a metal film, thereby forming the conductive core material 3.

Conductive cores can also be obtained by impregnating impregnated materials containing metal components into yarns (which may be multifilaments or monofilaments), woven fabrics or non-woven fabrics that are formed into yarns, strips, or twisted cords. The material 3 can also be formed.
Furthermore, a conductive filler (for example, graphite) is kneaded into a main material (for example, fluororesin) for shaping the conductive core 3 to form the conductive core 3. The method can also be adopted.

  The conductive core material 3 is left inserted into the hollow portion of the porous tube material 1 even after being used as a collector (that is, after the formation of the tube wall 2 and more specifically, after the production of the porous tube material 1). The Therefore, when the porous tube material 1 is distributed in this state (including the stock state), the conductive core material 3 acts as a shape-retaining material for the tube wall 2 as described above. In this way, the conductive core material 3 is expected to act as a shape-retaining material, and in that sense, it needs to be strong enough to back up the tube wall 2.

The release layer 4 is for urging the axial movement of the conductive core material 3. That is, when the porous tube material 1 is used, the conductive core material 3 can be easily removed (pulled out) from the hollow portion.
For example, the release layer 4 can be formed of a fluororesin or the like. Specific examples include polytetrafluoroethylene and tetrafluoroethylene / perfluoroalkyl vinyl ether copolymer. Many fluororesins have non-adhesive properties, and this property is preferable in that it is difficult for bacteria to adhere and mix. However, these are merely examples, and are not limited in any way, including the use of a resin other than a fluororesin (for example, a silicon resin). For example, the antibacterial property may be positively imparted to the release layer 4 by dispersing an antibacterial substance in the fluororesin.

  Various methods can be adopted as a method of providing the release layer 4 on the conductive core material 3. For example, a melt extrusion method in which a molten fluororesin is supplied toward a die passing through the conductive core material 3 and a fluororesin film is attached to the outer peripheral surface of the conductive core material 3, or the molten fluororesin is electrically conductive core A spraying method for spraying and adhering to the material 3 can be employed. In addition, it is possible to employ a dove dipping method by passing the conductive core material 3 through a pool in which a molten fluororesin is stored.

In these various methods, it is also possible to use a soluble resin (solution) instead of the meltable resin. When a soluble resin is used, a drying step, a curing agent application step, or the like may be attached as necessary in order to accelerate removal of the solvent and cause rapid and reliable curing.
In addition, when a wire material such as a covered electric wire (a wire material provided with an insulating coating such as a resin material from the beginning) is employed as the conductive core material 3, this coating portion can be made to act as the peeling layer 4.

Next, a method for manufacturing the porous tube material 1 according to the present invention (a method for forming the tube wall 2 by electrospinning) will be described.
In the electrospinning method, as shown in FIG. 2, a core material feeding device 10 that supplies the conductive core material 3 while keeping it in a straight state, and an injection hole that injects a polymer solution toward the linearly held conductive core material 3. And a charging device 12 that applies a high voltage with a potential difference between the conductive core member 3 and the nozzle 11 so that the conductive core member 3 becomes a collector. In addition, it is suitable for the nozzle 11 to connect the pump apparatus 13 which pressurizes and supplies a polymer solution toward an injection hole as needed.

  The core material feeding device 10 is configured to take up the conductive core material 3 with the take-up reel 16 while unwinding the conductive core material 3 from the take-up reel 15. Presented in the spinning method. The rotation of the take-up reel 15 and the take-up reel 16 is controlled by a drive control unit 17. In this drive control unit 17, the conductive core 3 is controlled by controlling the speed difference between the take-up reel 15 and the take-up reel 16 in principle such that [wind-up reel 15] ≦ [take-up reel 16]. Make sure to have proper tension.

  In FIG. 2, the charging device 12 is illustrated as applying the nozzle 11 side as a positive electrode and the conductive core material 3 side as a negative electrode. However, these polarities may be reversed, the positive electrode side, or the negative electrode. Either side may be grounded. In addition, a direct energization structure by sliding contact of an energization shoe or the like may be adopted for the conductive core material 3, or the reel drum 15 (or take-up reel 16) is made of metal and these reel cylinders are used. An indirect energization structure or the like may be employed.

  For the conductive core material 3 unwound from the unwinding reel 15, a melt extrusion device 18 or the like is installed on the primary side (left side of the nozzle 11 in FIG. 2) from the position where the electrospinning method is performed. The release layer 4 is formed on the material 3. Needless to say, when a conductive core material 3 having a release layer 4 from the beginning (such as a covered electric wire) is used, the step of forming the release layer 4 can be omitted.

  Under such an apparatus configuration, the conductive core material 3 is linearly fed from the unwinding reel 15 to the take-up reel 16 by the core material feeding device 10, and the conductive core material 3 and the nozzle 11 are A high voltage with a potential difference is applied between the two. As needed, the pump apparatus 13 is operated and the polymer solution supplied to the injection hole of the nozzle 11 is pressurized. When the conductive core material 3 is not provided with the release layer 4, the release layer 4 is formed on the conductive core material 3 in advance by the operation of the melt extrusion device 18 or the like.

  In the process in which the polymer solution is sprayed from the nozzle 11 toward the conductive core material 3 (sucked toward the conductive core material 3 side), the solution components are evaporated instantaneously and the polymer is further shaped while being shaped into ultrafine fibers. Nanofibers are formed, and the nanofibers are entangled and accumulated on the outer peripheral surface of the conductive core material 3. Thus, continuous air holes are formed in the nanofiber accumulation layer, and the tube wall 2 is formed (that is, the porous tube material 1 according to the present invention is manufactured).

  In such a manufacturing method of the porous tube 1, the electrospinning method is simultaneously performed while unwinding and winding the conductive core material 3 using the core material feeding device 10. This makes it possible to significantly reduce manufacturing costs. Therefore, for example, if a winding reel 15 having a long conductive core material 3 exceeding 100 m is prepared, a porous tube material 1 having the same length can be manufactured. It is excellent in productivity and enables cost reduction.

  The porous tube 1 wound around the take-up reel 16 is packaged or packed in a roll state in which the take-up reel 16 is removed from the wound state while being wound around the take-up reel 16. At this time, it is preferable that the porous tube material 1 is subjected to a sterilization process such as an autoclave sterilization process or an ultraviolet irradiation sterilization process, and then packaged or packed using a sterilized packaging material having low cytotoxicity.

  The porous tube material 1 that has been packaged or packed is preferably distributed (including a stock state) in that state. Then, in each use site (for example, a regenerative medical treatment site), the necessary length is cut out from the sterilization packaging or sterilization packaging each time, and the conductive core material 3 is taken out from the cut out and used. The take-out of the conductive core material 3 is facilitated by the release layer 4, and no effort is required.

  Note that the porous tube material 1 may be circulated as a wound state on the take-up reel 16 or a roll state removed from the take-up reel 16, or after the electrospinning without taking up the take-up reel 16. It is possible to circulate in the state of this sterilization packaging by performing sterilization packaging (packing, laminating, etc.) simultaneously in a constant size unit while cutting as it is with a constant size (for example, 100 to 300 mm).

Note that the feed speed of the conductive core material 3 in the core material feeding device 10 (drive control unit 17), the hole diameter and injection distance of the nozzle 11, the supply pressure of the pump device 13, the voltage of the charging device 12, and the like are as follows. The thickness can be appropriately changed according to the thickness, conductivity, and the required thickness of the tube wall 2 as the porous tube material 1.
For example, as shown in FIG. 3, a plurality of nozzles 11 may be provided in a ring arrangement around the conductive core material 3. In FIG. 3, four nozzles 11 are used and are arranged at equal intervals in the circumferential direction. Further, the two nozzles 11 facing each other with the conductive core material 3 interposed therebetween are arranged so as to face each other. With such an arrangement of the nozzles 11, nanofibers can be sprayed from a plurality of directions to the outer peripheral surface of the conductive core material 3, so that the thickness of the integrated layer (tube wall 2) is required. It can be said that it is preferable from the viewpoint of securing the amount (including the meaning of thickening) and increasing the production efficiency.

In FIG. 3, the number of the nozzles 11 is four, but there is no limitation in terms of the number. For example, the number of the nozzles 11 is only two in an opposing arrangement with the conductive core material 3 interposed therebetween, or six, eight, and twelve. For example, the number of nozzles 11 can be increased.
When the nozzles 11 are arranged opposite to each other with the conductive core material 3 interposed therebetween as described above, an action that makes it easier for the nanofibers to concentrate on the conductive core material 3 can be obtained. Therefore, there is an effect that a high-quality tube wall 2 can be obtained in which the generation of continuous pores is uniform as the accumulation layer and the wall thickness is uniform. However, it is not particularly limited to have an opposing arrangement with the conductive core material 3 interposed therebetween, and it is also possible to use an odd number (for example, three or five) of the nozzles 11 so as not to face each other. is there.

In addition, regarding the provision of the nozzles 11 in a ring-shaped arrangement around the conductive core material 3, the number of ring-shaped arrangements may be increased to a plurality in the length direction of the conductive core material 3. In this case, as the adjacent ring-shaped arrangement bodies, the arrangement angles of the respective nozzles 11 may be shifted.
For example, in the case where four nozzles 11 are provided in one ring-shaped arrangement, the nozzles 11 are arranged horizontally and vertically (0 °, 90 °, 180 °, 270 °) in the vertical ring-shaped arrangement. In the adjacent ring-shaped arrangement, the nozzle 11 is arranged by shifting the arrangement angle of the nozzle 11 by 45 ° (45 °, 135 °, 225 °, 315 °).

Of course, the number of ring-shaped arrangements is not limited, and can be three or four. Even in such a case, the arrangement angle of the nozzle 11 may be changed by 30 ° or 22.5 ° between the adjacent ring-shaped arrangements.
Furthermore, the plurality of nozzles 11 included in the ring-shaped arrangement body may be rotated around the conductive core member 3 (see arrow A in FIG. 3). When a plurality of ring-shaped arrangement bodies are provided, adjacent ring-shaped arrangement bodies may be rotated in reverse with each other, or may be integrally rotated.

In some cases, the conductive core member 3 may be rotated without rotating the ring-shaped arrangement body. That is, the conductive core material 3 is rotated by rotating the core material feeding device 10 as a whole (the unwinding reel 15 is rotated B and the take-up reel 16 is rotated C at the same speed).
As is apparent from the above description, in the porous tube 1 with a core material according to the present invention, the hollow portion of the porous tube material 1 is formed by the conductive core material 3 from the production through the distribution stage until it is used. The shape-retaining material is inserted. For this reason, even if an excessive external force is applied to the porous tube material 1 during distribution or the like, it is possible to prevent the porous tube material 1 from being broken or crushed. Therefore, it is not necessary to bulky and tightly package or pack the porous tube material 1 for distribution (to prevent deformation), and the distribution cost can be reduced. Naturally, the porous tube material 1 can be prevented from being discarded due to creases, crushing deformation, and the like, leading to cost reduction.

In addition, when using the porous tube 1 as an artificial blood vessel, the necessary length according to the treatment location can be cut and used each time, so cut loss (cutting and discarding useless length) is almost eliminated. There are advantages you can do.
In addition, the shape-retaining material used when the conductive core material 3 is distributed until the shape stabilization (so-called aging) is obtained against the shrinkage that occurs in the tube wall 2 of the porous tube material 1 due to sterilization treatment. Will act as. That is, even if the conductive core material 3 is removed at the site where the porous tube material 1 is used, shrinkage deformation hardly occurs, leading to the advantage that a high-quality porous tube material 1 can be obtained in terms of outer shape.

By the way, the present invention is not limited to the above-described embodiment, and can be appropriately changed according to the embodiment.
For example, the use as the porous tube material 1 is not limited at all. Further, the material for forming the porous tube 1 and the material used are not limited.
In the method for producing the porous tube 1 according to the present invention, when performing the electrospinning method, it is possible to combine some or all of the various methods (apparatuses) exemplified in FIG.

  In the cross-sectional shape in the longitudinal direction of the porous tube material 1, it is not limited that the thickness is constant (straight shape). For example, a thick portion and a thin portion are alternately or randomly generated, or a groove that is subdivided into a parallel or spiral shape in the longitudinal direction with respect to the inner peripheral surface (surface on the side in contact with the conductive core material 3) It may be a deformed type such as a streak or a continuous groove or streak. As described above, even when the radial layer is provided with an irregular shape, slipping property can be secured between the conductive core material 3 and the porous tube material 1 if the release layer 4 is provided. Therefore, there is no problem in pulling the conductive core material 3 from the porous tube material 1 during use.

DESCRIPTION OF SYMBOLS 1 Porous tube material 2 Tube wall 3 Conductive core material 4 Release layer 10 Core material feeder 11 Nozzle 12 Charging device 13 Pump device 15 Unwinding reel 16 Take-up reel 17 Drive control part 18 Melt extrusion apparatus

Claims (4)

A porous tubular material having a tubular shape in which a tube wall is formed by a nanofiber accumulation layer ;
A conductive core that fills a hollow portion surrounded by the tube wall with respect to the porous tube material and backs up the tube wall as a whole from the inside and has conductivity necessary as a collector of an electrospinning method when the tube wall is formed Material,
A packaging material or a packaging material for maintaining the porous tube material in a sterilized state with the conductive core material remaining as a shape retaining material for stabilizing the end of shrinkage deformation and preventing collapse deformation during circulation of the porous tube material; A porous tube material containing a core material, characterized by comprising:   The core material containing the core material according to claim 1, wherein a peeling layer is provided between the inner peripheral surface of the tube wall and the outer peripheral surface of the conductive core material to promote the axial movement of the conductive core material. Porous tube material.   The said core material is formed with the flexible metal wire, The core-containing porous pipe material of Claim 1 or Claim 2 characterized by the above-mentioned. By forming a tube wall with an accumulation layer of nanofibers by electrospinning around the conductive core material, the conductive core material fills the hollow portion formed in the tube wall and is totally backed up from the inside. Forming a porous tube,
Sterilizing the porous tube with the conductive core remaining in the hollow portion;
A method for producing a porous tube containing a core material, wherein the sterilized porous tube material is packaged or packed together with the conductive core material.

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