WO2023195038A1 - Embolization coil - Google Patents

Embolization coil Download PDF

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Publication number
WO2023195038A1
WO2023195038A1 PCT/JP2022/017023 JP2022017023W WO2023195038A1 WO 2023195038 A1 WO2023195038 A1 WO 2023195038A1 JP 2022017023 W JP2022017023 W JP 2022017023W WO 2023195038 A1 WO2023195038 A1 WO 2023195038A1
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WO
WIPO (PCT)
Prior art keywords
coil
filament
pores
aneurysm
embolic
Prior art date
Application number
PCT/JP2022/017023
Other languages
French (fr)
Japanese (ja)
Inventor
崇王 安齊
Original Assignee
テルモ株式会社
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Publication date
Application filed by テルモ株式会社 filed Critical テルモ株式会社
Priority to PCT/JP2022/017023 priority Critical patent/WO2023195038A1/en
Publication of WO2023195038A1 publication Critical patent/WO2023195038A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord

Definitions

  • the present invention relates to embolic coils.
  • Vascular embolization using embolization coils is a treatment method that embolizes blood vessels that supply nutrients to aneurysms and cancers in the brain.
  • a microcatheter is placed in a target blood vessel, and a platinum embolization coil is advanced from within the placed microcatheter using a coil delivery wire. This fills the embolic coil into the target blood vessel and embolizes the target blood vessel, such as a cerebral aneurysm.
  • Embolic coils include platinum coils and biological reaction coils, which are used depending on the case. Platinum coils are made by wrapping platinum wire around a platinum core wire, and the degree of flexibility changes depending on the hardness of the core wire. For example, a coil with a coil diameter of 0.010 inch (hereinafter referred to as size 10 for convenience) is thin and flexible and is therefore often used for relatively small cerebral aneurysms or ruptured cerebral aneurysms. A coil with a coil diameter of 0.018 inches (hereinafter referred to as size 18 for convenience) is often selected for unruptured cerebral aneurysms of 10 mm or more.
  • Relatively soft coils such as size 10 cause less stress on the cerebral aneurysm wall and can reduce the risk of intraoperative rupture, but recanalization after embolization becomes a problem.
  • a bioreactive coil the surface of the platinum coil is coated with lactic acid-glycolic acid copolymer (PLGA), which is a copolymer of polyglycolic acid (PGA) and polylactic acid (PLA), which are components of bioabsorbable sutures.
  • PLGA lactic acid-glycolic acid copolymer
  • PDA polylactic acid
  • Coiled coils are known. It is said that the absorption process of PLGA promotes thrombosis and organization. Coils with a structure opposite to this, in which polyglycolic acid threads are incorporated into the coils, are also known.
  • the bioreactive coil aims to accelerate the inflammatory phase until complete occlusion of the cerebral aneurysm (the maturation phase of tissue repair).
  • the vascular embolization device contains a biochemically active substance (an organization-promoting substance) in a resin wire placed in the lumen of an embolization coil of a cerebral aneurysm, and the endothelium at the entrance (neck) of the aneurysm is This makes it possible to promote the development of
  • PGA, PLGA, biochemically active substances, etc. may decompose and peel off and flow into the blood vessels, occluding the periphery of the cerebral blood vessels and causing cerebral infarction.
  • PGA, PLGA, and biochemically active substances may cause an excessive inflammatory reaction, which may prolong the period required for endothelialization.
  • the present invention has been made in order to solve the problems associated with the above-mentioned prior art, and provides an embolic coil that can shorten the period until complete occlusion of an aneurysm and endothelialization of the aneurysm entrance.
  • the purpose is to provide.
  • An embolic coil according to the present invention that achieves the above object includes a coil and a stretch resistance disposed in the inner lumen of the coil to prevent stretching of the coil.
  • the stretch resistance is constructed by fixing both ends of a filament made of non-biodegradable material to both ends of the coil.
  • the filament has a tensile strength of 60 g or more and a large number of pores with a diameter in the range of 20 to 40 ⁇ m, all of the pores having diameters within ⁇ 10%, which are arranged side by side, Each of the pores is porous and communicates with at least three other pores.
  • the filament functions as a stretch resistance and prevents the coil from stretching. Due to the pore structure of the filament, the inner part of the filament exhibits the effect of containing a large number of M1 macrophages (pro-inflammatory response) among the macrophages in the blood, and as a result, the area around the embolization coil contains M2 macrophages (pro-healing). The ratio is relatively high. Such polarization of macrophages shortens the period until complete occlusion of the aneurysm and endothelialization of the aneurysm entrance.
  • the filament is made of a non-biodegradable material, there is no risk that the material will decompose and peel off, flow into the blood vessel, and occlude the periphery. Therefore, it is possible to provide an embolization coil that can shorten the period until complete occlusion of an aneurysm and endothelialization of the entrance portion of the aneurysm.
  • FIG. 2 is a diagram schematically showing how an aneurysm is filled with an embolic coil according to an embodiment.
  • FIG. 3 is a side view showing the main parts of the embolic coil.
  • FIG. 2 is a perspective view schematically showing filaments forming the stretch resistance of the embolic coil.
  • FIG. 4 is an enlarged view of the portion surrounded by reference numeral 4 in FIG. 3, showing the pore structure of the filament. It is a figure which shows typically the manufacturing method of a filament.
  • FIG. 6 is an enlarged cross-sectional view schematically showing a part of the cross section taken along line 6A-6A in FIG. 5;
  • FIG. 6 is an enlarged cross-sectional view schematically showing a part of the cross section taken along line 6B-6B in FIG. 5;
  • FIG. 1 is a diagram schematically showing how an aneurysm 100 is filled with an embolic coil 10 according to an embodiment.
  • the tip of the microcatheter 110 is placed in the aneurysm 100, and then the microcatheter 110 is inserted from the proximal end of the indwelled microcatheter 110.
  • a coil delivery wire with an embolic coil 10 fixed at the tip is inserted into the lumen and advanced.
  • the embolic coil 10 is placed within the aneurysm 100 from the tip of the microcatheter 110, it is remotely detached from the delivery wire. This detachment is performed, for example, by a method of melting the resin filament fixing the embolic coil 10 by applying electricity to an electric heating coil formed at the tip of the delivery wire.
  • the step of arranging the embolic coils 10 is repeated depending on the size of the aneurysm 100, and the aneurysm 100 is filled with a plurality of embolic coils 10 until it is densely filled.
  • FIG. 2 is a side view showing the main parts of the embolic coil 10.
  • 3 is a perspective view schematically showing a filament 40 constituting the stretch resistance 30 of the embolic coil 10
  • FIG. 4 is an enlarged view of the portion surrounded by the reference numeral 4 in FIG. 3, showing the pore structure of the filament 40. It is.
  • the embolic coil 10 generally includes a coil 20 and a stretch resistance 30 that is disposed in the lumen of the coil 20 and prevents the coil 20 from stretching.
  • the stretch resistance 30 is constructed by fixing both ends of a filament 40 made of a non-biodegradable material to both ends of the coil 20.
  • the filament 40 has a tensile strength of 60 g or more, and has a large number of pores 41 with a diameter in the range of 20 to 40 ⁇ m, all of which have diameters within ⁇ 10%, which are arranged side by side.
  • Each of the pores 41 is made of a porous body in communication with at least three other pores 41 .
  • the wire diameter of the wire 21 forming the coil 20 is approximately 0.02 to 0.12 mm from the viewpoint of insertion or retention in a tube.
  • the coil diameter of the coil 20 is approximately 0.1 to 1.0 mm.
  • the length of the coil 20 is approximately 20 mm to 400 mm.
  • the constituent material of the coil 20 is not particularly limited, but includes, for example, metals (radio-opaque materials) such as cobalt alloys, tantalum, tungsten, iridium, gold, platinum, and tungsten, or alloys containing these (for example, platinum-iridium alloys). ) and the like are preferably used.
  • metals radio-opaque materials
  • the embolic coil 10 has contrast properties, and the position of the embolic coil 10 and the aneurysm can be seen under radiofluoroscopy. This is preferable because it can be inserted into the living body while checking the filling status.
  • Both ends of the filament 40 are fixed to both ends of the coil 20.
  • the fixing method is not limited, for example, it may be fixed by being wrapped around the wire 21 of the coil 20 with a tungsten wire, or fixed to both ends of the coil 20 with an adhesive.
  • the material constituting the filament 40 is preferably a non-biodegradable and flexible material.
  • the constituent material of the filament 40 can be a metal or a resin material, but a resin material is preferable from the viewpoint of manufacturing a pore structure to be described later.
  • the resin material needs to be a material that is not decomposed in vivo.
  • the resin composition constituting the filament 40 includes polyolefin, polyethylene, polyolefin elastomer, ethylene-octene copolymer, polyethylene terephthalate (PET), nylon, and amide, which are materials used as coil elongation prevention filaments.
  • Base polymers, block copolymers, polyether block amide copolymers (for example, PEBAX (registered trademark) manufactured by Arkema), and polypropylene are preferably used.
  • the tensile strength of the stretch resistance is 60 g or more. Therefore, from the viewpoint of making the filament 40 function as a stretch resistance, it is preferable that the tensile strength of the filament 40 is 60 g or more. Tensile strength can be measured using a tensile strength tester.
  • the diameter of the filament 40 is not particularly limited as long as it can be inserted into the inner cavity of the coil 20, but the diameter is preferably 150 to 500 ⁇ m (micro meters) is preferred.
  • the filament 40 has a substantially uniform inner diameter with a large number of pores 41 ranging in diameter from 20 to 40 ⁇ m, with all diameters falling within ⁇ 10 percent. It is a porous body in which pores 41 having pores 41 are arranged in an array, and each pore 41 communicates with at least three other pores 41 .
  • FIG. 4 shows a cross-section perpendicular to the axis of a filament 40 of a porous body having the above-described pore structure.
  • the circle designated by numeral 41 indicates a large number of pores 41 with diameters in the range of 20-40 ⁇ m, all of which are within ⁇ 10 percent of the diameter.
  • the respective pores 41 are arranged in a close-packed array.
  • Three ellipses indicated by the reference numeral 42 in one pore 41 indicate communication holes 42 in which adjacent pores 41 contact each other and communicate with each other at the contact point. Furthermore, two ellipses indicated by the reference numeral 42a in one communication hole 42 indicate the communication hole 42a that can be seen further into the back side through the communication hole 42.
  • all diameters of the pores 41 fall within ⁇ 10%.
  • substantially all the pores 41 communicate with at least three other pores 41, but the pores 41 located on the outer surface of the filament 40 communicate with other adjacent pores 41. Since the number of pores 41 is limited, it is also permissible that the number of other pores communicating with each other is less than three.
  • Each of the pores 41 communicates with 3 to 12 other pores 41. Most preferably, excluding the pore 41 exposed on the outer surface of the filament 40, the filament 40 communicates with 6 or 12 other pores 41. In this embodiment, as shown in FIG. 4, the center communicates with three pores on the back side, communicates with three pores in the front, and further communicates with six pores surrounding the sides. It communicates with a total of 12 pores.
  • the tissue repair process after coil embolization is similar to the healing process of a skin wound, passing through the inflammatory phase ⁇ proliferation phase ⁇ maturation phase, and then neointimal formation and healing is completed.
  • the filament 40 of the porous body of this embodiment having the above-described pore structure has the effect of shortening the period required for tissue repair (neointimal formation) through the inflammatory phase ⁇ proliferation phase ⁇ maturation phase.
  • the mechanism is that due to the pore structure of the filament 40, the inner part of the filament 40 takes in a large number of M1 macrophages (inflammatory reaction promoting) among the macrophages in the blood, and as a result, the macrophages surrounding the embolic coil 10 become M2 macrophages.
  • M1 macrophages produce inflammatory cytokines and M2 macrophages produce anti-inflammatory cytokines. It is thought that the polarization of macrophages enables complete occlusion of the aneurysm 100, healing of the entrance of the aneurysm 100, and completion of endothelialization at an early stage. Such an effect is particularly noticeable in the diameter range of pores 41 of 20 to 40 ⁇ m.
  • the embolic coil 10 of this embodiment configured as described above promotes not only an inflammatory response but also a healing response to the occlusion of the aneurysm 100 due to the pore structure of the filament 40. Therefore, it is possible to reduce the possibility that the period until complete occlusion will be prolonged or that endothelialization will become insufficient due to the persistence of the inflammatory reaction.
  • the filament 40 has both a healing promoting function and a coil elongation prevention (stretch resistance) function, it is possible to maintain good operability as the embolic coil 10 and reduce the occurrence of aneurysm perforation, etc. due to the embolic coil 10 during surgery. .
  • the filament 40 is flexible, it can be applied to either a size 10 coil or a size 18 coil.
  • the filament 40 is made of a non-biodegradable material, there is no possibility that the material will decompose and flow into the bloodstream and occlude the periphery.
  • FIG. 5 is a diagram schematically showing a method of manufacturing the filament 40.
  • 6A is a cross-sectional view taken along line 6A-6A in FIG. 5
  • FIG. 6B is a cross-sectional view taken along line 6B-6B in FIG.
  • Each cross-sectional view schematically shows a portion of the cross section perpendicular to the longitudinal axis of the filament 40 in an enlarged manner.
  • the filament 40 manufacturing machine 200 includes a supply section 203 that supplies a raw material solution 201 of the resin composition constituting the filament 40 and a pore forming material 202 for forming pores 41, and a raw material solution A pore structure is formed by a nozzle 205 that discharges a mixed liquid 204 in the form of a thread, which is a mixture of 201 and a pore-forming material 202, and a tank 208 that stores a solvent 207 through which the raw material thread 206 discharged from the nozzle 205 passes. and a product roller 209 for winding up the filament 40.
  • the resin composition constituting the filament 40 is as described above.
  • the pore-forming material 202 preferably has a true spherical shape with a diameter in the range of 20 to 40 ⁇ m, and all diameters are within ⁇ 10%.
  • the pore-forming material 202 preferably has a hardness that allows it to maintain a true spherical shape during molding.
  • the pore-forming material 202 is dissolved in a solvent 207 that does not dissolve the resin composition constituting the filament 40.
  • the pore-forming material 202 is preferably formed from polymethyl methacrylate or polystyrene, and the solvent 207 used for dissolution is preferably, for example, tetrahydrofuran or chloroform.
  • the shape of the discharge port of the nozzle 205 and the discharge pressure for discharging the mixed liquid 204 are adjusted so that the pore formers 202 mixed in the raw material solution 201 are brought into uniform contact with each other.
  • the tank 208 is filled with a solvent 207 that dissolves only the pore-forming material 202 .
  • the inner diameter of the nozzle 205 defines the outer diameter of the filament 40, but the inner diameter of the nozzle 205 is an integral multiple of the outer diameter of the pore former 202 so that the pore former 202 is uniformly arranged within the filament 40. This is desirable.
  • the pore formers 202 mixed in the raw material solution 201 are in uniform contact with each other. While the raw material yarn 206 is being moved through the solvent 207 in the tank 208, only the pore-forming material 202 is gradually dissolved and removed from the raw material yarn 206. As shown in FIG. 6B, when the raw material yarn 206 is pulled up from the solvent 207 in the tank 208, all of the pore-forming material 202 has been dissolved and removed. As a result, a porous filament 40 having a pore structure in which a plurality of pores 41 are interconnected and arranged in an array is obtained.
  • the cross section of the filament 40 may not be circular but may be square or rectangular with one side being an integral multiple of the outer diameter of the pore forming material 202.
  • the filament 40 may be finished by polishing or cutting the surface of the ejection-molded filament. Also good.
  • the embolic coil 10 of this embodiment includes the coil 20 and the stretch resistance 30 that is disposed in the inner cavity of the coil 20 and prevents the coil 20 from being stretched.
  • the stretch resistance 30 is constructed by fixing both ends of a filament 40 made of a non-biodegradable material to both ends of the coil 20.
  • the filament 40 has a tensile strength of 60 g or more, and has a large number of pores 41 with a diameter in the range of 20 to 40 ⁇ m, all of which have diameters within ⁇ 10%, which are arranged side by side. It is a porous body in which each of the pores 41 communicates with at least three other pores 41 .
  • the filament 40 since the filament 40 has a tensile strength of 60 g or more, the filament 40 can function as the stretch resistance 30 and the coil 20 can be prevented from stretching. There is no need to provide a separate stretch resistance. Further, due to the characteristic pore structure of the filament 40, the inner part of the filament 40 takes in many M1 macrophages (inflammatory reaction promoting) among macrophages in the blood, and as a result, the outer part of the filament 40 (the embolic coil 10 The blood around the area has a high proportion of M2 macrophages (promoting healing).
  • Such polarization of macrophages has the effect of shortening the period required for tissue repair (neointimal formation) through the inflammatory phase, proliferation phase, and maturation phase.
  • tissue repair neointimal formation
  • the period until the aneurysm 100 is completely occluded and the entrance of the aneurysm 100 becomes endothelialized is shortened.
  • the filament 40 is made of a non-biodegradable material, there is no risk that the material will decompose and peel off, flow into the blood vessel, and occlude the periphery. Therefore, it is possible to provide an embolic coil 10 that can shorten the period until complete occlusion of the aneurysm 100 and endothelialization of the entrance portion of the aneurysm 100.
  • all of the pores 41 have a substantially uniform inner diameter, such that the diameter is within ⁇ 10 percent.
  • the pore structure of the filament 40 becomes uniform, and the effect of shortening the period required for tissue repair (neointimal formation) can be reliably exerted.
  • the filament 40 has a diameter of 150 to 500 ⁇ m. With this configuration, a good balance of characteristics such as the function of preventing expansion of the coil 20 and flexibility can be achieved.
  • Each of the pores 41 communicates with 3 to 12 other pores 41.
  • the pores excluding the pores near the surface of the filament 40 communicate with the other 6 or 12 pores 41 .
  • the resin composition constituting the filament 40 is selected from polyolefin, polyethylene, polyolefin elastomer, ethylene-octene copolymer, polyethylene terephthalate, nylon, amide-based polymer, block copolymer, polyether block amide copolymer, and polypropylene.
  • a flexible filament 40 made of a non-biodegradable material can be obtained.
  • the shape of the coil 20 is easily changed, and intra-aneurysmal embolization in which the embolic coil 10 is filled into the aneurysm 100 can be easily performed.
  • embolic coil according to the present invention has been described above through the embodiments and modified examples, the present invention is not limited to each configuration described, and can be modified as appropriate based on the description of the claims. It is.
  • Embolic coil 20 Coil 21 Wire 30 Stretch resistance 40 Filament 41 Pore 42 Communication hole 42a Communication hole 100 Aneurysm 110 Microcatheter 200 Manufacturing machine 201 Raw material solution 202 Pore-forming material 203 Supply section 204 Mixed liquid 205 Nozzle 206 Raw material thread 207 Manufacturing Solvent 208 that dissolves only the porous material Tank 209 Product roller

Abstract

The purpose the present invention is to provide an embolization coil that can shorten the period until complete occlusion of an aneurysm or endothelialization of an aneurysm entry point is reached. This embolization coil (10) comprises a coil (20) and a stretch resistance (30) that is disposed in the inner cavity of the coil and prevents stretching of the coil. The stretch resistance is formed by fixing both ends of a filament (40) comprising a non-biodegradable material to both ends of the coil. The filament has a tensile strength of 60 g or higher and comprises a porous body in which a plurality of pores (41) having a diameter in the range of 20-40 μm, with all of the pore diameters ranging within ±10 percent of one another, are disposed in rows and each pore communicates with at least three other pores.

Description

塞栓コイルembolic coil
　本発明は、塞栓コイルに関する。 The present invention relates to embolic coils.
　脳などの動脈瘤や癌に養分を供給する血管を塞栓する治療法として、塞栓コイルを使用する血管塞栓術がある。このような血管塞栓術においては、マイクロカテーテルを標的となる血管内に留置し、留置したマイクロカテーテル内からプラチナ製の塞栓コイルをコイルデリバリーワイヤーによって前進させる。これによって、塞栓コイルを標的血管内に充填し、脳動脈瘤などの標的血管を塞栓する。 Vascular embolization using embolization coils is a treatment method that embolizes blood vessels that supply nutrients to aneurysms and cancers in the brain. In such vascular embolization, a microcatheter is placed in a target blood vessel, and a platinum embolization coil is advanced from within the placed microcatheter using a coil delivery wire. This fills the embolic coil into the target blood vessel and embolizes the target blood vessel, such as a cerebral aneurysm.
　塞栓コイルには、プラチナコイルと、生体反応コイルとがあり、症例に応じて使い分けられている。プラチナコイルは、プラチナ芯線にプラチナ線を巻き付けたもので芯線の硬さにより柔軟度が変わる。例えば、コイル径０．０１０インチ（以下、便宜的に１０サイズと呼ぶ）のコイルは細くて柔軟であるため比較的小さな脳動脈瘤や破裂脳動脈瘤で用いられることが多い。コイル径０．０１８インチ（以下、便宜的に１８サイズと呼ぶ）のコイルは１０ｍｍ以上の未破裂脳動脈瘤において選択されることが多い。１０サイズのような比較的柔らかいコイルは脳動脈瘤壁に対するストレスが少なく術中破裂の危険性を減少することができるが、塞栓後の再開通が問題となる。生体反応コイルとしては、生体吸収性縫合糸の成分であるポリグリコール酸（ＰＧＡ）とポリ乳酸（ＰＬＡ）との共重合体である乳酸・グリコール酸共重合体（ＰＬＧＡ）によってプラチナコイルの表面を被ったコイルが知られている。ＰＬＧＡの吸収過程で血栓化、器質化を促進すると言われている。これとは逆の構造となった、ポリグリコール酸糸をコイルに組み込んだコイルも知られている。生体反応コイルは、脳動脈瘤の完全閉塞（組織修復でいう成熟期）までにおける炎症期を亢進させることを狙ったものである。 Embolic coils include platinum coils and biological reaction coils, which are used depending on the case. Platinum coils are made by wrapping platinum wire around a platinum core wire, and the degree of flexibility changes depending on the hardness of the core wire. For example, a coil with a coil diameter of 0.010 inch (hereinafter referred to as size 10 for convenience) is thin and flexible and is therefore often used for relatively small cerebral aneurysms or ruptured cerebral aneurysms. A coil with a coil diameter of 0.018 inches (hereinafter referred to as size 18 for convenience) is often selected for unruptured cerebral aneurysms of 10 mm or more. Relatively soft coils such as size 10 cause less stress on the cerebral aneurysm wall and can reduce the risk of intraoperative rupture, but recanalization after embolization becomes a problem. As a bioreactive coil, the surface of the platinum coil is coated with lactic acid-glycolic acid copolymer (PLGA), which is a copolymer of polyglycolic acid (PGA) and polylactic acid (PLA), which are components of bioabsorbable sutures. Coiled coils are known. It is said that the absorption process of PLGA promotes thrombosis and organization. Coils with a structure opposite to this, in which polyglycolic acid threads are incorporated into the coils, are also known. The bioreactive coil aims to accelerate the inflammatory phase until complete occlusion of the cerebral aneurysm (the maturation phase of tissue repair).
　下記特許文献１に係る血管塞栓用具は、脳動脈瘤の塞栓コイルのルーメンに配置する樹脂線材に生化学的活性物質（器質化促進物質）を含有させ、動脈瘤の入口（ネック）部の内皮化を促進可能としている。 The vascular embolization device according to Patent Document 1 below contains a biochemically active substance (an organization-promoting substance) in a resin wire placed in the lumen of an embolization coil of a cerebral aneurysm, and the endothelium at the entrance (neck) of the aneurysm is This makes it possible to promote the development of
特許６７０８２００号公報Patent No. 6708200
　しかしながら、ＰＧＡ、ＰＬＧＡ、生化学的活性物質などが分解剥離、血管内に流出し、脳血管の末梢を閉塞し脳梗塞を起こす虞がある。また、ＰＧＡ、ＰＬＧＡ、生化学的活性物質によって、炎症反応が過剰なものとなり、内皮化までの所要期間がかえって長期化してしまう虞がある。 However, there is a risk that PGA, PLGA, biochemically active substances, etc. may decompose and peel off and flow into the blood vessels, occluding the periphery of the cerebral blood vessels and causing cerebral infarction. In addition, PGA, PLGA, and biochemically active substances may cause an excessive inflammatory reaction, which may prolong the period required for endothelialization.
　本発明は、上記従来技術に伴う課題を解決するためになされたものであり、動脈瘤の完全閉塞、動脈瘤の入口部の内皮化に至るまでの期間を短縮することが可能な塞栓コイルを提供することを目的とする。 The present invention has been made in order to solve the problems associated with the above-mentioned prior art, and provides an embolic coil that can shorten the period until complete occlusion of an aneurysm and endothelialization of the aneurysm entrance. The purpose is to provide.
　上記目的を達成する本発明に係る塞栓コイルは、コイルと、前記コイルの内腔に配置され前記コイルの伸張を防止するストレッチレジスタンスと、を有する。前記ストレッチレジスタンスは、非生分解性材料からなるフィラメントの両端を前記コイルの両端に固定することによって構成される。前記フィラメントは、引張強度が６０ｇ以上であり、かつ、直径が２０～４０μｍの範囲内の多数の細孔であって、すべての直径が±１０パーセント以内に収まる前記細孔が並べて配置され、前記細孔のそれぞれが少なくとも他の３つの前記細孔と連通している多孔質からなる。 An embolic coil according to the present invention that achieves the above object includes a coil and a stretch resistance disposed in the inner lumen of the coil to prevent stretching of the coil. The stretch resistance is constructed by fixing both ends of a filament made of non-biodegradable material to both ends of the coil. The filament has a tensile strength of 60 g or more and a large number of pores with a diameter in the range of 20 to 40 μm, all of the pores having diameters within ±10%, which are arranged side by side, Each of the pores is porous and communicates with at least three other pores.
　本発明に係る塞栓コイルによれば、フィラメントがストレッチレジスタンスとしての機能を発揮し、コイルの伸張を防止する。フィラメントの細孔構造によって、フィラメント内方部分が血液中のマクロファージのうちのＭ１マクロファージ（炎症反応促進性）を多く含む作用を発揮し、その結果、塞栓コイルの周囲はＭ２マクロファージ（治癒促進性）の比率が比較的高い状態になる。このようなマクロファージの極性化によって、動脈瘤の完全閉塞や動脈瘤の入口部の内皮化に至るまでの期間が短縮される。しかも、フィラメントは非生分解性材料からなるため、材料が分解剥離して血管内に流出し末梢を閉塞する虞もない。よって、動脈瘤の完全閉塞、動脈瘤の入口部の内皮化に至るまでの期間を短縮することが可能な塞栓コイルを提供できる。 According to the embolic coil according to the present invention, the filament functions as a stretch resistance and prevents the coil from stretching. Due to the pore structure of the filament, the inner part of the filament exhibits the effect of containing a large number of M1 macrophages (pro-inflammatory response) among the macrophages in the blood, and as a result, the area around the embolization coil contains M2 macrophages (pro-healing). The ratio is relatively high. Such polarization of macrophages shortens the period until complete occlusion of the aneurysm and endothelialization of the aneurysm entrance. Furthermore, since the filament is made of a non-biodegradable material, there is no risk that the material will decompose and peel off, flow into the blood vessel, and occlude the periphery. Therefore, it is possible to provide an embolization coil that can shorten the period until complete occlusion of an aneurysm and endothelialization of the entrance portion of the aneurysm.
実施形態に係る塞栓コイルを動脈瘤内に充填している様子を模式的に示す図である。FIG. 2 is a diagram schematically showing how an aneurysm is filled with an embolic coil according to an embodiment. 塞栓コイルの要部を示す側面図である。FIG. 3 is a side view showing the main parts of the embolic coil. 塞栓コイルのストレッチレジスタンスを構成するフィラメントを模式的に示す斜視図である。FIG. 2 is a perspective view schematically showing filaments forming the stretch resistance of the embolic coil. 図３の符号４によって囲まれる部分を拡大し、フィラメントの細孔構造を示す図である。FIG. 4 is an enlarged view of the portion surrounded by reference numeral 4 in FIG. 3, showing the pore structure of the filament. フィラメントの製造法を模式的に示す図である。It is a figure which shows typically the manufacturing method of a filament. 図５の６Ａ－６Ａ線に沿う断面の一部分を拡大して模式的に示す断面図である。FIG. 6 is an enlarged cross-sectional view schematically showing a part of the cross section taken along line 6A-6A in FIG. 5; 図５の６Ｂ－６Ｂ線に沿う断面の一部分を拡大して模式的に示す断面図である。FIG. 6 is an enlarged cross-sectional view schematically showing a part of the cross section taken along line 6B-6B in FIG. 5;
　以下、添付した図面を参照しながら、本発明の実施形態およびその変形例を説明する。なお、以下の記載は特許請求の範囲に記載される技術的範囲や用語の意義を限定するものではない。また、図面の寸法比率は説明の都合上誇張されており、実際の比率とは異なる場合がある。 Hereinafter, embodiments of the present invention and modifications thereof will be described with reference to the attached drawings. Note that the following description does not limit the technical scope or meaning of terms described in the claims. Further, the dimensional ratios in the drawings are exaggerated for convenience of explanation and may differ from the actual ratios.
　（塞栓コイル１０）
　図１は、実施形態に係る塞栓コイル１０を動脈瘤１００内に充填している様子を模式的に示す図である。 (Embolization coil 10)
FIG. 1 is a diagram schematically showing how an aneurysm 100 is filled with an embolic coil 10 according to an embodiment.
　図１に示すように、塞栓コイル１０を動脈瘤１００内に充填する場合、マイクロカテーテル１１０の先端を動脈瘤１００内に留置し、続いて、留置したマイクロカテーテル１１０の基端からマイクロカテーテル１１０のルーメン内に塞栓コイル１０が先端に固定されたコイルデリバリーワイヤーを挿入し、前進させる。塞栓コイル１０は、マイクロカテーテル１１０の先端から動脈瘤１００内に配置されるとデリバリーワイヤーから遠隔的に離脱される。この離脱は、例えばデリバリーワイヤーの先端に形成された電熱コイルに通電することによって塞栓コイル１０を固定していた樹脂製フィラメントを溶融する方法により行われる。塞栓コイル１０の配置工程は、動脈瘤１００のサイズに応じて繰り返し行われ、複数の塞栓コイル１０により動脈瘤１００内が密になるまで充填される。 As shown in FIG. 1, when filling the aneurysm 100 with the embolic coil 10, the tip of the microcatheter 110 is placed in the aneurysm 100, and then the microcatheter 110 is inserted from the proximal end of the indwelled microcatheter 110. A coil delivery wire with an embolic coil 10 fixed at the tip is inserted into the lumen and advanced. Once the embolic coil 10 is placed within the aneurysm 100 from the tip of the microcatheter 110, it is remotely detached from the delivery wire. This detachment is performed, for example, by a method of melting the resin filament fixing the embolic coil 10 by applying electricity to an electric heating coil formed at the tip of the delivery wire. The step of arranging the embolic coils 10 is repeated depending on the size of the aneurysm 100, and the aneurysm 100 is filled with a plurality of embolic coils 10 until it is densely filled.
　図２は、塞栓コイル１０の要部を示す側面図である。図３は、塞栓コイル１０のストレッチレジスタンス３０を構成するフィラメント４０を模式的に示す斜視図、図４は、図３の符号４によって囲まれる部分を拡大し、フィラメント４０の細孔構造を示す図である。 FIG. 2 is a side view showing the main parts of the embolic coil 10. 3 is a perspective view schematically showing a filament 40 constituting the stretch resistance 30 of the embolic coil 10, and FIG. 4 is an enlarged view of the portion surrounded by the reference numeral 4 in FIG. 3, showing the pore structure of the filament 40. It is.
　図２、図３、および図４に示すように、塞栓コイル１０は、概説すると、コイル２０と、コイル２０の内腔に配置されコイル２０の伸張を防止するストレッチレジスタンス３０と、を有する。ストレッチレジスタンス３０は、非生分解性材料からなるフィラメント４０の両端をコイル２０の両端に固定することによって構成される。フィラメント４０は、引張強度が６０ｇ以上であり、かつ、直径が２０～４０μｍの範囲内の多数の細孔４１であって、すべての直径が±１０パーセント以内に収まる細孔４１が並べて配置され、細孔４１のそれぞれが少なくとも他の３つの細孔４１と連通している多孔質体からなる。以下、塞栓コイル１０の構成を詳述する。 As shown in FIGS. 2, 3, and 4, the embolic coil 10 generally includes a coil 20 and a stretch resistance 30 that is disposed in the lumen of the coil 20 and prevents the coil 20 from stretching. The stretch resistance 30 is constructed by fixing both ends of a filament 40 made of a non-biodegradable material to both ends of the coil 20. The filament 40 has a tensile strength of 60 g or more, and has a large number of pores 41 with a diameter in the range of 20 to 40 μm, all of which have diameters within ±10%, which are arranged side by side. Each of the pores 41 is made of a porous body in communication with at least three other pores 41 . The configuration of the embolic coil 10 will be described in detail below.
　（コイル２０）
　コイル２０を形成する線材２１の素線径は、管内に挿入または留置する観点から、０．０２～０．１２ｍｍ程度である。コイル２０のコイル径としては、０．１～１．０ｍｍ程度である。コイル２０の長さは、２０ｍｍ～４００ｍｍ程度である。 (Coil 20)
The wire diameter of the wire 21 forming the coil 20 is approximately 0.02 to 0.12 mm from the viewpoint of insertion or retention in a tube. The coil diameter of the coil 20 is approximately 0.1 to 1.0 mm. The length of the coil 20 is approximately 20 mm to 400 mm.
　コイル２０の構成材料としては、特に限定されないが、例えば、コバルト系合金、タンタル、タングステン、イリジウム、金、白金、タングステン等の金属（放射線不透過材料）またはこれらを含む合金（例えば白金－イリジウム合金）等のような化学的に安定な材料を用いるのが好ましい。特に、Ｘ線等の放射線を実質的に透過しない放射線不透過材料からコイル２０を構成した場合には、塞栓コイル１０に造影性が得られ、放射線透視下で塞栓コイル１０の位置や動脈瘤の充填状況などを確認しつつ生体内に挿入することができ、好ましい。 The constituent material of the coil 20 is not particularly limited, but includes, for example, metals (radio-opaque materials) such as cobalt alloys, tantalum, tungsten, iridium, gold, platinum, and tungsten, or alloys containing these (for example, platinum-iridium alloys). ) and the like are preferably used. In particular, when the coil 20 is made of a radiopaque material that does not substantially transmit radiation such as X-rays, the embolic coil 10 has contrast properties, and the position of the embolic coil 10 and the aneurysm can be seen under radiofluoroscopy. This is preferable because it can be inserted into the living body while checking the filling status.
　（フィラメント４０）
　フィラメント４０は、その両端がコイル２０の両端に固定される。固定方法は問わないが、例えば、タングステンワイヤによってコイル２０の線材２１に巻き付け固定されたり、接着剤によってコイル２０の両端に固定されたりする。 (filament 40)
Both ends of the filament 40 are fixed to both ends of the coil 20. Although the fixing method is not limited, for example, it may be fixed by being wrapped around the wire 21 of the coil 20 with a tungsten wire, or fixed to both ends of the coil 20 with an adhesive.
　フィラメント４０を構成する材料は、非生分解性材料であって、柔軟な材料であることが好ましい。フィラメント４０の構成材料は、金属または樹脂材料を適用できるが、後述する細孔構造を製造する観点からは樹脂材料であることが好ましい。樹脂材料の材質は、生体内では分解されない材料とすることが必要である。具体的には、フィラメント４０を構成する樹脂組成物は、コイル伸長防止用フィラメントとして用いられている材料である、ポリオレフィン、ポリエチレン、ポリオレフィンエラストマー、エチレン－オクテンコポリマー、ポリエチレンテレフタレート（ＰＥＴ）、ナイロン、アミドベースのポリマー、ブロックコポリマー、ポリエーテルブロックアミド共重合体（例えば、アルケマ社製のＰＥＢＡＸ（登録商標））、ポリプロピレンが好適に用いられる。 The material constituting the filament 40 is preferably a non-biodegradable and flexible material. The constituent material of the filament 40 can be a metal or a resin material, but a resin material is preferable from the viewpoint of manufacturing a pore structure to be described later. The resin material needs to be a material that is not decomposed in vivo. Specifically, the resin composition constituting the filament 40 includes polyolefin, polyethylene, polyolefin elastomer, ethylene-octene copolymer, polyethylene terephthalate (PET), nylon, and amide, which are materials used as coil elongation prevention filaments. Base polymers, block copolymers, polyether block amide copolymers (for example, PEBAX (registered trademark) manufactured by Arkema), and polypropylene are preferably used.
　一般的な塞栓コイル１０のプラチナコイルにあっては、ストレッチレジスタンスの引張強度は６０ｇ以上である。そこで、フィラメント４０をストレッチレジスタンスとして機能させる観点から、フィラメント４０の引張強度は６０ｇ以上であることが好ましい。引張強度は、引張強度試験機により測定することができる。 In the platinum coil of the general embolic coil 10, the tensile strength of the stretch resistance is 60 g or more. Therefore, from the viewpoint of making the filament 40 function as a stretch resistance, it is preferable that the tensile strength of the filament 40 is 60 g or more. Tensile strength can be measured using a tensile strength tester.
　フィラメント４０の直径は、コイル２０の内腔に挿入できる大きさであればよく、特に制限されないが、コイル２０の伸張を防止する機能や柔軟性などの特性バランスから、直径が１５０～５００μｍ（マイクロメートル）であることが好ましい。 The diameter of the filament 40 is not particularly limited as long as it can be inserted into the inner cavity of the coil 20, but the diameter is preferably 150 to 500 μm (micro meters) is preferred.
　図３および図４に示すように、フィラメント４０は、直径が２０～４０μｍの範囲内の多数の細孔４１であって、すべての直径が±１０パーセント以内に収まるような実質的に均一の内径を有する細孔４１がアレイ状に並べて配置され、細孔４１のそれぞれが少なくとも他の３つの細孔４１と連通している多孔質体である。図４には、上記した細孔構造を有する多孔質体のフィラメント４０の軸直交断面が示される。符号４１によって示される円は、直径が２０～４０μｍの範囲内の多数の細孔４１であって、すべての直径が±１０パーセント以内に収まる細孔４１を示している。それぞれの細孔４１は最密状態にアレイ状に並べて配置された状態となっている。１つの細孔４１の中に符号４２によって示される３個の楕円は、隣り合う細孔４１同士が接触し、接点において隣り合う細孔４１同士を連通する連通孔４２を示している。さらに、１つの連通孔４２の中に符号４２ａによって示される２個の楕円は、連通孔４２を通してさらに奥側に見える連通孔４２ａを示している。 As shown in FIGS. 3 and 4, the filament 40 has a substantially uniform inner diameter with a large number of pores 41 ranging in diameter from 20 to 40 μm, with all diameters falling within ±10 percent. It is a porous body in which pores 41 having pores 41 are arranged in an array, and each pore 41 communicates with at least three other pores 41 . FIG. 4 shows a cross-section perpendicular to the axis of a filament 40 of a porous body having the above-described pore structure. The circle designated by numeral 41 indicates a large number of pores 41 with diameters in the range of 20-40 μm, all of which are within ±10 percent of the diameter. The respective pores 41 are arranged in a close-packed array. Three ellipses indicated by the reference numeral 42 in one pore 41 indicate communication holes 42 in which adjacent pores 41 contact each other and communicate with each other at the contact point. Furthermore, two ellipses indicated by the reference numeral 42a in one communication hole 42 indicate the communication hole 42a that can be seen further into the back side through the communication hole 42.
　均一な細孔構造とするため、細孔４１のすべての直径が±１０パーセント以内に収まることが好ましい。 In order to have a uniform pore structure, it is preferable that all diameters of the pores 41 fall within ±10%.
　なお、本実施形態において、実質的にすべての細孔４１がそれぞれ少なくとも他の３つの細孔４１と連通しているが、フィラメント４０の外表面に位置する細孔４１については、隣り合う他の細孔４１の数に限りがあるため、連通する他の細孔の数が３より少ない場合も許容される。 In this embodiment, substantially all the pores 41 communicate with at least three other pores 41, but the pores 41 located on the outer surface of the filament 40 communicate with other adjacent pores 41. Since the number of pores 41 is limited, it is also permissible that the number of other pores communicating with each other is less than three.
　細孔４１のそれぞれは、他の３～１２個の細孔４１と連通する。最も好ましくは、フィラメント４０の外表面に露出した細孔４１を除いて、他の６個もしくは１２個の細孔４１と連通するものである。本実施形態においては、図４に示されるように中心より奥側に３個の細孔と連通し、手前に同様に３個の細孔と連通し、さらに側面を囲む６個の細孔と連通するため、計１２個の細孔と連通している。 Each of the pores 41 communicates with 3 to 12 other pores 41. Most preferably, excluding the pore 41 exposed on the outer surface of the filament 40, the filament 40 communicates with 6 or 12 other pores 41. In this embodiment, as shown in FIG. 4, the center communicates with three pores on the back side, communicates with three pores in the front, and further communicates with six pores surrounding the sides. It communicates with a total of 12 pores.
　コイル塞栓術後の組織修復過程は、皮膚創傷の治癒過程と同様であり、炎症期→増殖期→成熟期を経て、新生内膜化して治癒が完了する。上記した細孔構造を有する本実施形態の多孔質体のフィラメント４０は、炎症期→増殖期→成熟期を経て、組織修復（新生内膜化）するのに要する期間を短縮する作用がある。そのメカニズムは、フィラメント４０の細孔構造によって、フィラメント４０の内方部分が血中のマクロファージのうちのＭ１マクロファージ（炎症反応促進性）を多く取り込み、その結果、塞栓コイル１０の周囲のマクロファージはＭ２マクロファージ（治癒促進性）の比率が高い状態に極性化されるからであると考えられる。Ｍ１マクロファージは炎症性サイトカインを産生し、Ｍ２マクロファージは抗炎症性サイトカインを産生する。マクロファージの極性化によって、動脈瘤１００の完全閉塞や動脈瘤１００の入口部の治癒、内皮化が早期に完了すると考えられる。このような作用は、細孔４１の直径２０～４０μｍの範囲において特に顕著に現れる。 The tissue repair process after coil embolization is similar to the healing process of a skin wound, passing through the inflammatory phase → proliferation phase → maturation phase, and then neointimal formation and healing is completed. The filament 40 of the porous body of this embodiment having the above-described pore structure has the effect of shortening the period required for tissue repair (neointimal formation) through the inflammatory phase → proliferation phase → maturation phase. The mechanism is that due to the pore structure of the filament 40, the inner part of the filament 40 takes in a large number of M1 macrophages (inflammatory reaction promoting) among the macrophages in the blood, and as a result, the macrophages surrounding the embolic coil 10 become M2 macrophages. This is thought to be because the ratio of macrophages (promoting healing) is polarized to a high state. M1 macrophages produce inflammatory cytokines and M2 macrophages produce anti-inflammatory cytokines. It is thought that the polarization of macrophages enables complete occlusion of the aneurysm 100, healing of the entrance of the aneurysm 100, and completion of endothelialization at an early stage. Such an effect is particularly noticeable in the diameter range of pores 41 of 20 to 40 μm.
　なお、現在のところ、特定の細孔構造においてマクロファージの極性化が生じる詳細なメカニズムについては明確に解明するには至っていない。 Note that, at present, the detailed mechanism by which macrophage polarization occurs in a specific pore structure has not been clearly elucidated.
　上記のように構成される本実施形態の塞栓コイル１０は、フィラメント４０の細孔構造によって、動脈瘤１００の閉塞に対し、炎症反応の亢進のみならず、治癒反応の促進を促すものである。そのため、炎症反応の持続による完全閉塞までの期間が延長したり、内皮化が不全になったりする虞を軽減できる。 The embolic coil 10 of this embodiment configured as described above promotes not only an inflammatory response but also a healing response to the occlusion of the aneurysm 100 due to the pore structure of the filament 40. Therefore, it is possible to reduce the possibility that the period until complete occlusion will be prolonged or that endothelialization will become insufficient due to the persistence of the inflammatory reaction.
　また、フィラメント４０が治癒促進機能とコイル伸長防止（ストレッチレジスタンス）機能を併せ持つことによって、塞栓コイル１０としての操作性を良好に保ち、術中の塞栓コイル１０による瘤穿孔等の発生を減らすことができる。 Furthermore, since the filament 40 has both a healing promoting function and a coil elongation prevention (stretch resistance) function, it is possible to maintain good operability as the embolic coil 10 and reduce the occurrence of aneurysm perforation, etc. due to the embolic coil 10 during surgery. .
　また、フィラメント４０は柔軟であるため、１０サイズのコイル、１８サイズのコイルのいずれにも適用できる。 Furthermore, since the filament 40 is flexible, it can be applied to either a size 10 coil or a size 18 coil.
　また、フィラメント４０は非生分解性材料から構成されているため、材料が分解し、血流中に流れて末梢を閉塞するといった事態が生じない。 Furthermore, since the filament 40 is made of a non-biodegradable material, there is no possibility that the material will decompose and flow into the bloodstream and occlude the periphery.
　（フィラメント４０の製造方法）
　図５は、フィラメント４０の製造法を模式的に示す図である。図６Ａは、図５の６Ａ－６Ａ線に沿う断面図であり、図６Ｂは、図５の６Ｂ－６Ｂ線に沿う断面図である。いずれの断面図もフィラメント４０の長手軸に直交する断面の一部分を拡大して模式的に示すものである。 (Method for manufacturing filament 40)
FIG. 5 is a diagram schematically showing a method of manufacturing the filament 40. 6A is a cross-sectional view taken along line 6A-6A in FIG. 5, and FIG. 6B is a cross-sectional view taken along line 6B-6B in FIG. Each cross-sectional view schematically shows a portion of the cross section perpendicular to the longitudinal axis of the filament 40 in an enlarged manner.
　図５に示すように、フィラメント４０の製造機２００は、フィラメント４０を構成する樹脂組成物の原料溶液２０１および細孔４１を形成するための造孔材２０２を供給する供給部２０３と、原料溶液２０１と造孔材２０２とを混和させた混合液２０４を糸状に吐出するノズル２０５と、ノズル２０５から吐出された原料糸２０６を通過させる溶媒２０７を貯めたタンク２０８と、細孔構造が形成されたフィラメント４０を巻き取る製品ローラ２０９と、を有する。 As shown in FIG. 5, the filament 40 manufacturing machine 200 includes a supply section 203 that supplies a raw material solution 201 of the resin composition constituting the filament 40 and a pore forming material 202 for forming pores 41, and a raw material solution A pore structure is formed by a nozzle 205 that discharges a mixed liquid 204 in the form of a thread, which is a mixture of 201 and a pore-forming material 202, and a tank 208 that stores a solvent 207 through which the raw material thread 206 discharged from the nozzle 205 passes. and a product roller 209 for winding up the filament 40.
　フィラメント４０を構成する樹脂組成物は上記したとおりである。造孔材２０２は、直径が２０～４０μｍの範囲内の真球形状を有し、すべての直径が±１０パーセント以内に収まることが好ましい。造孔材２０２は、成形時に真球状を維持できる硬度を有することが好ましい。造孔材２０２は、フィラメント４０を構成する樹脂組成物を溶解しない溶媒２０７に溶解する。造孔材２０２は、例えば、ポリメチルメタクリレートやポリスチレンから形成することが好ましく、溶解に使用する溶媒２０７は、例えば、テトラヒドロフラン、クロロホルムなどが好ましい。ノズル２０５の吐出口形状や混合液２０４を吐出させる吐出圧は、原料溶液２０１に混和した造孔材２０２同士を均一に接触させるように調整されている。タンク２０８には、造孔材２０２のみを溶解させる溶媒２０７が充填されている。ノズル２０５の内径は、フィラメント４０の外径を定義するが、フィラメント４０内に均一に造孔材２０２が配置されるように、ノズル２０５の内径は造孔材２０２の外径の整数倍とすることが望ましい。 The resin composition constituting the filament 40 is as described above. The pore-forming material 202 preferably has a true spherical shape with a diameter in the range of 20 to 40 μm, and all diameters are within ±10%. The pore-forming material 202 preferably has a hardness that allows it to maintain a true spherical shape during molding. The pore-forming material 202 is dissolved in a solvent 207 that does not dissolve the resin composition constituting the filament 40. The pore-forming material 202 is preferably formed from polymethyl methacrylate or polystyrene, and the solvent 207 used for dissolution is preferably, for example, tetrahydrofuran or chloroform. The shape of the discharge port of the nozzle 205 and the discharge pressure for discharging the mixed liquid 204 are adjusted so that the pore formers 202 mixed in the raw material solution 201 are brought into uniform contact with each other. The tank 208 is filled with a solvent 207 that dissolves only the pore-forming material 202 . The inner diameter of the nozzle 205 defines the outer diameter of the filament 40, but the inner diameter of the nozzle 205 is an integral multiple of the outer diameter of the pore former 202 so that the pore former 202 is uniformly arranged within the filament 40. This is desirable.
　図６Ａに示すように、ノズル２０５から吐出された原料糸２０６は、原料溶液２０１に混和した造孔材２０２同士が均一に接触している。この原料糸２０６をタンク２０８内の溶媒２０７中を移動させている間に、造孔材２０２のみが徐々に溶解し、原料糸２０６から除去される。図６Ｂに示すように、原料糸２０６をタンク２０８内の溶媒２０７から引き上げたときには、すべての造孔材２０２が溶解除去されている。これにより、複数の細孔４１が相互に連通しアレイ状に配置された細孔構造を有する多孔質体のフィラメント４０が得られる。 As shown in FIG. 6A, in the raw material yarn 206 discharged from the nozzle 205, the pore formers 202 mixed in the raw material solution 201 are in uniform contact with each other. While the raw material yarn 206 is being moved through the solvent 207 in the tank 208, only the pore-forming material 202 is gradually dissolved and removed from the raw material yarn 206. As shown in FIG. 6B, when the raw material yarn 206 is pulled up from the solvent 207 in the tank 208, all of the pore-forming material 202 has been dissolved and removed. As a result, a porous filament 40 having a pore structure in which a plurality of pores 41 are interconnected and arranged in an array is obtained.
　なお、上記した製造工程で可能な限り細孔４１を隙間無く形成するため、フィラメント４０の断面を円形ではなく、一辺が造孔材２０２の外径の整数倍となる正方形もしくは長方形としても良い。また、製造されたフィラメント４０の外表面に造孔材２０２が配置されず、細孔４１が形成されない場合には、吐出成形されたフィラメントの表面を研磨もしくは切除するなどしてフィラメント４０を仕上げても良い。 Note that in order to form the pores 41 as closely as possible in the above manufacturing process, the cross section of the filament 40 may not be circular but may be square or rectangular with one side being an integral multiple of the outer diameter of the pore forming material 202. In addition, if the pore-forming material 202 is not placed on the outer surface of the manufactured filament 40 and the pores 41 are not formed, the filament 40 may be finished by polishing or cutting the surface of the ejection-molded filament. Also good.
　（塞栓コイル１０の効果）
　以上説明したように、本実施形態の塞栓コイル１０は、コイル２０と、コイル２０の内腔に配置されコイル２０の伸張を防止するストレッチレジスタンス３０と、を有する。ストレッチレジスタンス３０は、非生分解性材料からなるフィラメント４０の両端をコイル２０の両端に固定することによって構成されている。フィラメント４０は、引張強度が６０ｇ以上であり、かつ、直径が２０～４０μｍの範囲内の多数の細孔４１であって、すべての直径が±１０パーセント以内に収まる細孔４１が並べて配置され、細孔４１のそれぞれが少なくとも他の３つの細孔４１と連通している多孔質体である。 (Effect of embolic coil 10)
As described above, the embolic coil 10 of this embodiment includes the coil 20 and the stretch resistance 30 that is disposed in the inner cavity of the coil 20 and prevents the coil 20 from being stretched. The stretch resistance 30 is constructed by fixing both ends of a filament 40 made of a non-biodegradable material to both ends of the coil 20. The filament 40 has a tensile strength of 60 g or more, and has a large number of pores 41 with a diameter in the range of 20 to 40 μm, all of which have diameters within ±10%, which are arranged side by side. It is a porous body in which each of the pores 41 communicates with at least three other pores 41 .
　このように構成した塞栓コイル１０によれば、フィラメント４０は引張強度が６０ｇ以上であるため、フィラメント４０にストレッチレジスタンス３０としての機能を発揮させ、コイル２０の伸張を防止することができる。別途のストレッチレジスタンスを設ける必要はない。また、フィラメント４０の特徴的な細孔構造によって、フィラメント４０の内方部分が血中のマクロファージのうちのＭ１マクロファージ（炎症反応促進性）を多く取り込み、その結果、フィラメント４０の外側（塞栓コイル１０の周囲）の血液はＭ２マクロファージ（治癒促進性）の比率が高い状態になる。このようなマクロファージの極性化によって、炎症期→増殖期→成熟期を経て、組織修復（新生内膜化）するのに要する期間を短縮する作用が発揮される。この結果、動脈瘤１００の完全閉塞や動脈瘤１００の入口部の内皮化に至るまでの期間が短縮される。しかも、フィラメント４０は非生分解性材料からなるため、材料が分解剥離して血管内に流出し末梢を閉塞する虞もない。よって、動脈瘤１００の完全閉塞、動脈瘤１００の入口部の内皮化に至るまでの期間を短縮することが可能な塞栓コイル１０を提供できる。 According to the embolic coil 10 configured in this way, since the filament 40 has a tensile strength of 60 g or more, the filament 40 can function as the stretch resistance 30 and the coil 20 can be prevented from stretching. There is no need to provide a separate stretch resistance. Further, due to the characteristic pore structure of the filament 40, the inner part of the filament 40 takes in many M1 macrophages (inflammatory reaction promoting) among macrophages in the blood, and as a result, the outer part of the filament 40 (the embolic coil 10 The blood around the area has a high proportion of M2 macrophages (promoting healing). Such polarization of macrophages has the effect of shortening the period required for tissue repair (neointimal formation) through the inflammatory phase, proliferation phase, and maturation phase. As a result, the period until the aneurysm 100 is completely occluded and the entrance of the aneurysm 100 becomes endothelialized is shortened. Furthermore, since the filament 40 is made of a non-biodegradable material, there is no risk that the material will decompose and peel off, flow into the blood vessel, and occlude the periphery. Therefore, it is possible to provide an embolic coil 10 that can shorten the period until complete occlusion of the aneurysm 100 and endothelialization of the entrance portion of the aneurysm 100.
　細孔４１のすべては、直径が±１０パーセント以内に収まるような実質的に均一の内径を有することが好ましい。このように構成すれば、フィラメント４０の細孔構造が均一になり、組織修復（新生内膜化）するのに要する期間を短縮する作用を確実に発揮させることができる。 Preferably, all of the pores 41 have a substantially uniform inner diameter, such that the diameter is within ±10 percent. With this configuration, the pore structure of the filament 40 becomes uniform, and the effect of shortening the period required for tissue repair (neointimal formation) can be reliably exerted.
　フィラメント４０は、直径が１５０～５００μｍである。このように構成すれば、コイル２０の伸張を防止する機能や柔軟性などの特性バランスが良好にできる。 The filament 40 has a diameter of 150 to 500 μm. With this configuration, a good balance of characteristics such as the function of preventing expansion of the coil 20 and flexibility can be achieved.
　細孔４１のそれぞれは、他の３～１２個の細孔４１と連通してなる。特に好ましくは、フィラメント４０の表面近くの細孔を除いて、他の６個もしくは１２個の細孔４１と連通するものである。 Each of the pores 41 communicates with 3 to 12 other pores 41. Particularly preferably, the pores excluding the pores near the surface of the filament 40 communicate with the other 6 or 12 pores 41 .
　フィラメント４０を構成する樹脂組成物がポリオレフィン、ポリエチレン、ポリオレフィンエラストマー、エチレン－オクテンコポリマー、ポリエチレンテレフタレート、ナイロン、アミドベースのポリマー、ブロックコポリマー、ポリエーテルブロックアミド共重合体、ポリプロピレンから選択されてなる。このように構成すれば、非生分解性材料からなる柔軟なフィラメント４０を得ることができる。その結果、コイル２０の形状が変化し易くなり、塞栓コイル１０を動脈瘤１００内に充填する瘤内塞栓術を容易に実施できる。 The resin composition constituting the filament 40 is selected from polyolefin, polyethylene, polyolefin elastomer, ethylene-octene copolymer, polyethylene terephthalate, nylon, amide-based polymer, block copolymer, polyether block amide copolymer, and polypropylene. With this configuration, a flexible filament 40 made of a non-biodegradable material can be obtained. As a result, the shape of the coil 20 is easily changed, and intra-aneurysmal embolization in which the embolic coil 10 is filled into the aneurysm 100 can be easily performed.
　以上、実施形態および変形例を通じて本発明に係る塞栓コイルを説明したが、本発明は説明した各構成のみに限定されるものでなく、特許請求の範囲の記載に基づいて適宜変更することが可能である。 Although the embolic coil according to the present invention has been described above through the embodiments and modified examples, the present invention is not limited to each configuration described, and can be modified as appropriate based on the description of the claims. It is.
１０　　塞栓コイル
２０　　コイル
２１　　線材
３０　　ストレッチレジスタンス
４０　　フィラメント
４１　　細孔
４２　　連通孔
４２ａ　連通孔
１００　動脈瘤
１１０　マイクロカテーテル
２００　製造機
２０１　原料溶液
２０２　造孔材
２０３　供給部
２０４　混合液
２０５　ノズル
２０６　原料糸
２０７　造孔材のみを溶解する溶媒
２０８　タンク
２０９　製品ローラ 10 Embolic coil 20 Coil 21 Wire 30 Stretch resistance 40 Filament 41 Pore 42 Communication hole 42a Communication hole 100 Aneurysm 110 Microcatheter 200 Manufacturing machine 201 Raw material solution 202 Pore-forming material 203 Supply section 204 Mixed liquid 205 Nozzle 206 Raw material thread 207 Manufacturing Solvent 208 that dissolves only the porous material Tank 209 Product roller

Claims (4)

  1. 　コイルと、
    　前記コイルの内腔に配置され前記コイルの伸張を防止するストレッチレジスタンスと、を有する塞栓コイルであって、
    　前記ストレッチレジスタンスは、非生分解性材料からなるフィラメントの両端を前記コイルの両端に固定することによって構成され、
    　前記フィラメントは、
    　　引張強度が６０ｇ以上であり、かつ、
    　　直径が２０～４０μｍの範囲内の多数の細孔であって、すべての直径が±１０パーセント以内に収まる前記細孔が並べて配置され、前記細孔のそれぞれが少なくとも他の３つの前記細孔と連通している多孔質体である、塞栓コイル。     coil and
    an embolic coil having a stretch resistance disposed in a lumen of the coil to prevent stretching of the coil;
    The stretch resistance is constructed by fixing both ends of a filament made of a non-biodegradable material to both ends of the coil,
    The filament is
    has a tensile strength of 60 g or more, and
    a plurality of pores having diameters in the range of 20 to 40 μm, all having diameters within ±10 percent, arranged side by side, each of said pores having at least three other said pores; An embolic coil is a porous body that communicates with the body.
  2. 　前記フィラメントは、直径が１５０～５００μｍである、請求項１に記載の塞栓コイル。 The embolic coil according to claim 1, wherein the filament has a diameter of 150 to 500 μm.
  3. 　前記細孔は、前記フィラメントの表面に設けられたものを除いて、それぞれが他の６個もしくは１２個の前記細孔と連通してなる、請求項２に記載の塞栓コイル。 The embolic coil according to claim 2, wherein each of the pores, excluding those provided on the surface of the filament, communicates with the other 6 or 12 pores.
  4. 　前記フィラメントを構成する樹脂組成物がポリオレフィン、ポリエチレン、ポリオレフィンエラストマー、エチレン－オクテンコポリマー、ポリエチレンテレフタレート、ナイロン、アミドベースのポリマー、ブロックコポリマー、ポリエーテルブロックアミド共重合体、ポリプロピレンから選択されてなる、請求項１～３のいずれか１項に記載の塞栓コイル。 The resin composition constituting the filament is selected from polyolefin, polyethylene, polyolefin elastomer, ethylene-octene copolymer, polyethylene terephthalate, nylon, amide-based polymer, block copolymer, polyether block amide copolymer, polypropylene. The embolic coil according to any one of Items 1 to 3.
PCT/JP2022/017023 2022-04-04 2022-04-04 Embolization coil WO2023195038A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009525137A (en) * 2006-02-02 2009-07-09 ボストン サイエンティフィック リミテッド Porous material used in aneurysms
US20120253381A1 (en) * 2011-03-31 2012-10-04 Codman & Shurtleff, Inc. Occlusive device with porous structure and stretch resistant member
US20170245865A1 (en) * 2014-09-15 2017-08-31 Donald K. Jones Intralumenal Occlusion Devices Having Improved Properties

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009525137A (en) * 2006-02-02 2009-07-09 ボストン サイエンティフィック リミテッド Porous material used in aneurysms
US20120253381A1 (en) * 2011-03-31 2012-10-04 Codman & Shurtleff, Inc. Occlusive device with porous structure and stretch resistant member
US20170245865A1 (en) * 2014-09-15 2017-08-31 Donald K. Jones Intralumenal Occlusion Devices Having Improved Properties

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHAU SARAH M., HERTING SCOTT M., NOLTENSMEYER DILLON A., AHMED HAMZAH, MAITLAND DUNCAN J., RAGHAVAN SHREYA: "Macrophage activation in response to shape memory polymer foam-coated aneurysm occlusion devices", JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B: APPLIED BIOMATERIALS, JOHN WILEY & SONS , HOBOKEN NJ, US, vol. 110, no. 7, 1 July 2022 (2022-07-01), US , pages 1535 - 1544, XP093097126, ISSN: 1552-4973, DOI: 10.1002/jbm.b.35015 *
JAMES D. BRYERS; CECILIA M. GIACHELLI; BUDDY D. RATNER: "Engineering biomaterials to integrate and heal: The biocompatibility paradigm shifts", BIOTECHNOLOGY AND BIOENGINEERING, JOHN WILEY, HOBOKEN, USA, vol. 109, no. 8, 24 May 2012 (2012-05-24), Hoboken, USA, pages 1898 - 1911, XP071096655, ISSN: 0006-3592, DOI: 10.1002/bit.24559 *

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