WO2024001718A1 - 封堵植入物及其制备方法 - Google Patents

封堵植入物及其制备方法 Download PDF

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Publication number
WO2024001718A1
WO2024001718A1 PCT/CN2023/099317 CN2023099317W WO2024001718A1 WO 2024001718 A1 WO2024001718 A1 WO 2024001718A1 CN 2023099317 W CN2023099317 W CN 2023099317W WO 2024001718 A1 WO2024001718 A1 WO 2024001718A1
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WO
WIPO (PCT)
Prior art keywords
coil
wire
degradable
implant according
occlusion implant
Prior art date
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PCT/CN2023/099317
Other languages
English (en)
French (fr)
Inventor
顾家镭
卢俊
刘伟
王雪琴
岳斌
Original Assignee
上海微创医疗器械（集团）有限公司
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Publication of WO2024001718A1 publication Critical patent/WO2024001718A1/zh

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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
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
    • A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
    • A61B17/12113—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel within an aneurysm
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • 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
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12099—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
    • A61B17/12109—Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder in a blood vessel
    • 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
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
    • A61B17/1214—Coils or wires
    • A61B17/12145—Coils or wires having a pre-set deployed three-dimensional shape
    • 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
    • A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
    • A61B17/1214—Coils or wires
    • A61B17/1215—Coils or wires comprising additional materials, e.g. thrombogenic, having filaments, having fibers, being coated
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/146—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00526—Methods of manufacturing

Definitions

  • the present application relates to the technical field of medical devices, and in particular to a blocking implant and a preparation method thereof.
  • Spring coil is a blocking implant for arterial fistulas and aneurysms. It is also commonly used for emergency closure of blood vessels when blood vessels are accidentally damaged and bleeding during surgical operations. The mechanism of action of spring coils is to reduce local blood flow velocity and promote thrombosis. , thereby playing a blocking role.
  • Commonly used spring coils are mainly divided into bare metal spring coils, hydrogel metal spring coils and metal spring coils with polymer fluff.
  • commonly used spring coils have mature and effective blocking effects, because the metal cannot be degraded, it will still remain in the body to form a mass effect after the arterial fistula or aneurysm heals, and the compression on other blood vessels or nerves cannot be relieved.
  • degradable spring coils have been developed in the field, the current degradable spring coil technology is not mature enough, and there is still a risk of blood vessel or aneurysm recanalization.
  • the present application provides a occlusion implant and a preparation method thereof.
  • An occlusive implant including:
  • a first coil is composed of a braided material, the braided material includes at least a first filament, and the first filament is an electrospun yarn prepared by electrospinning;
  • the second coil disposed inside the first coil, the second coil including a developing material and a polymer material;
  • An anti-unrotation component connected to at least one of the first coil and the second coil.
  • At least one of the proximal end and the distal end of the first coil is closed.
  • the braided material includes at least a first wire and a second wire, and the first wire and the second wire have different degradation rates.
  • the material of the first wire is selected from at least one of poly-L-lactic acid and polypropyl caproate
  • the material of the second wire is selected from the group consisting of polydioxanone, At least one of polylactic acid and polyglycolic acid.
  • At least a portion of the anti-unspin component is disposed inside the second coil.
  • the anti-untwisting component includes an anti-untwisting section and a connecting section, and the anti-untwisting section is located at the The connecting section is located inside the second coil, and the connecting section is located outside the proximal end of the second coil.
  • the material of the anti-unspin component is a degradable material.
  • the material of the anti-unspin component is selected from the group consisting of polydioxanone, racemic polylactic acid, polyglycolic acid, poly-L-lactic acid, polyglycolic acid, polylactic acid copolymer, and polypropylene caproate. At least one of ester and polydioxanone.
  • the mass ratio of the developing material to the polymer material in the second coil is approximately between 1:2 and 4:1.
  • the polymer material in the second coil includes a degradable wire, the degradable wire is wound into a spiral coil, and the coil pitch of the degradable wire is equal to the diameter of the degradable wire.
  • the ratio is between 1:1 and 4:1.
  • the polymer material in the second coil includes a non-degradable wire, the non-degradable wire is wound into a spiral coil, and the coil pitch of the non-degradable wire is equal to the diameter of the non-degradable wire.
  • the ratio is between 2:1 and 8:1.
  • a method for preparing a blocking implant including the following steps:
  • the first coil and the second coil are shaped, and an anti-unrotation component is connected to at least one of the first coil and the second coil.
  • At least one of the proximal end and the distal end of the first coil is sealed by hot melt sealing.
  • Degradable material is applied to at least one of the proximal and distal ends of the first coil after heat melting, and then at least one of the proximal and distal ends of the first coil is cooled by cooling the degradable material. Closed processing.
  • At least one of the proximal end and the distal end of the first coil is placed in the mold, and polydioxanone, racemic polylactic acid, polyglycolic acid, poly-L-lactic acid, polyglycolic acid, and polylactic acid are copolymerized
  • At least one of polypropylene caproate and polydioxanone is heat-melted in the mold, and at least one of the proximal end and the distal end of the first coil is cooled after heat-melting. Closed processing.
  • Figure 1 is a schematic cross-sectional view of the first part of the occlusion implant provided by some embodiments of the present application;
  • Figure 2 is a schematic cross-sectional view of the second part of the occlusion implant provided by some embodiments of the present application.
  • distal end is defined here to mean the end far away from the operator during the surgical operation
  • proximal end means the end close to the operator during the surgical operation.
  • the occlusion implant includes a first coil 100, a second coil 300 and an anti-unrotation component 200.
  • the first coil The coil 100 is composed of a braided material, the braided material includes at least a first filament, the first filament is an electrospun yarn prepared by electrospinning, and the second coil 300 is disposed on the Inside the first coil 100, the second coil includes a developing material and a polymer material, and the anti-unspin component is connected to at least one of the first coil and the second coil.
  • Occlusion implant package Including substances used to block arterial fistulas and aneurysms, such as medical spring coils, blocking nets and other structures.
  • the first coil 100 and the second coil of the blocking implant 300 refers to a spiral coil structure formed along a spiral shape.
  • the first coil 100 and the second coil 300 of the occlusion implant can also be formed along a mesh structure.
  • the first coil 100 may include at least one unit coil layer 110 , and the unit coil layer 110 may be knitted by at least one knitting material.
  • the first coil 100 may be made of multiple layers of unit coil layers 110 . Because each unit coil layer 110 is made of knitted material, the first coil 100 is also made of knitted material.
  • the interior of the first coil 100 and the second coil 300 can be understood as the inner coils of the first coil 100 and the second coil 300 and the gap between the coils and other structures, which are not limited here.
  • the first coil 100 of the occlusion implant is the main part of the occlusion implant that performs the occlusion function.
  • the first coil 100 is woven through a braiding process, and the braided material contains a first wire. Using the first wire
  • the surface of the first coil 100 formed by combining the knitting process has a rough texture and structure. The rough texture and structure can accelerate the speed of thrombosis and have a good thrombogenic effect, quickly promote thrombosis in a short period of time, and effectively reduce the risk of arterial fistulas.
  • the porous structure can support the growth and adhesion of cells, and can be used as a cell growth scaffold in the medium and long term, speeding up endothelialization and promoting lesion healing, which can effectively solve the risk of blood vessel or aneurysm recanalization.
  • the knitting process used to form the first coil 100 can be any weaving method.
  • the weaving process can be a two-ply braiding with one strand pressed against one strand, a three-ply braided with one strand pressed against two strands, or a two-ply braided with two strands pressed against two strands.
  • the spacing between braiding repeating units can be 0.5 to 10 times the diameter of the wire.
  • the proximal end 120 of the first coil or the distal end 130 of the first coil may be sealed, when at least one of the proximal end 120 of the first coil and the distal end 130 of the first coil is sealed. Afterwards, the blocking effect on the blood vessels can be formed.
  • the sealing treatment method can adopt various forms, for example, the proximal end 120 of the first coil and the distal end 130 of the first coil are sealed by hot melt sealing.
  • polydioxanone (PPDO), racemic polylactic acid (PDLLA), polyglycolic acid (PGA), poly-L-lactic acid (PLLA), polyglycolic acid/polylactic acid copolymer can be used for hot melt sealing.
  • Degradable materials such as (PLGA), polypropyl caproate (PCL) and polydioxanone (PDO) are heat-melted in the mold, and then the proximal end 120 of the first coil and the first coil are cooled.
  • the distal end 130 of a coil is sealed.
  • This sealing method can also improve the performance of the proximal end 120 of the first coil or the distal end 130 of the first coil.
  • the softness forms a relatively soft end structure, so that when the proximal end 120 of the first coil or the distal end 130 of the first coil contacts the blood vessel wall, the blood vessel will not be damaged or punctured.
  • the braided material used for braiding the first coil 100 can also be braided by combining the first wire material with other second wire materials.
  • the braided material It contains at least two materials: a first wire material and a second wire material, wherein the materials of the first wire material and the second wire material can be respectively selected as degradable materials with different degradation rates. Therefore, the first coil 100 It has a degradable effect and can reduce the long-term space-occupying effect.
  • first wire and the second wire in the braided material have different degradation rates, which can cause the first coil 100 to form a relay degradation effect in the body, that is, The first wire and the second wire in the braided material degrade successively at different degradation rates, which can shorten the patient's recovery period while reducing the risk of sealing failure and blood flow recanalization.
  • the first wire material and the second wire material have different degradation rates.
  • the material of the first wire material may include a degradable material with a degradation rate of 2 to 4 years, and the second wire material
  • the material of the material can include degradable materials with a degradation rate within 1.5 years. Therefore, when the sealing implant passes through the body within 1.5 years, the braided wire material can degrade first. At this time, the first wire material has not completely degraded, and the second wire material has not yet completely degraded.
  • the degradation of the second wire can reduce the mass effect, while the retention of the first wire can continue to perform the blocking function and reduce the risk of blocking failure and blood flow recanalization. Therefore, through two different degradation rates, the occupying effect can be balanced. The problem of recanalization risk due to position effect has resulted in good therapeutic effects.
  • the material of the first wire includes any one or a combination of poly-L-lactic acid and polypropyl caproate, and the material of the second wire includes polydioxanone,
  • the material of the second wire includes polydioxanone
  • any one or combination of polylactic acid and polyglycolic acid those skilled in the art can also select other materials according to needs, which are not limited here.
  • the anti-untwisting component 200 can prevent the first coil 100 from being straightened under the action of external force to achieve the anti-untwisting function.
  • the anti-untwisting component 200 can adopt any structural form.
  • the anti-untwisting component 200 includes an anti-untwisting section 210 and a connecting section 220.
  • the anti-untwisting section 210 is located inside the first coil 100
  • the connecting section 220 is located inside the first coil.
  • the outside of the proximal end 120, wherein the anti-untwisting component 200 can be composed of one or more anti-untwisting wires, for example, one anti-untwisting wire is folded in half, and the two ends of the anti-untwisting wire are merged Together, it can be called the distal end of the anti-untwisting thread.
  • the anti-untwisting thread can be seen on the right side in Figure 1. At this time, the anti-untwisting thread will form a ring structure on the left side in Figure 2.
  • the proximal end of the anti-untwisting wire can be called the proximal end of the anti-untwisting wire, and the distal end of the anti-untwisting wire can be threaded along the inside of the first coil 100 from the proximal end to the distal direction, and the distal end of the anti-untwisting wire can be fixed on The distal end 130 of the first coil, and the proximal end of the anti-untwisting wire is used to form an annular structure outside the proximal end 120 of the first coil.
  • the length of the annular structure can be between 0.5-3 mm and is located inside the first coil 100
  • the portion may constitute the anti-untwisting section 210 of the anti-untwisting component 200
  • the exposed annular structure may constitute the connecting section 220 of the anti-untwisting component 200 .
  • the material of the anti-unspin part 200 can be degradable materials or non-degradable materials.
  • the material of the anti-unspin component 200 may include degradable polydioxanone, racemic polylactic acid, polyglycolic acid, poly-L-lactic acid, polyglycolic acid, polylactic acid copolymer, polycapric acid Any one or combination of propyl ester and polydioxanone.
  • the anti-untwisting component may be connected to the first coil or the second coil, wherein the connection of the anti-untwisting component may be a detachable connection or a non-detachable connection.
  • the anti-unrotation component 200 can also be At least a part may be disposed inside the first coil 100 .
  • the material of the second coil 300 can be selected according to functional requirements.
  • the material of the second coil 300 is a degradable material, or the material of the second coil 300 is a non-degradable material, or , the material of the second coil 300 includes a developing material and a polymer material, and the polymer can be a degradable material or a non-degradable material.
  • the material of the second coil 300 includes a developing material and a polymer material. It can be understood that the material of the second coil 300 includes a layered structure formed by a developing material and a layered structure formed by a polymer material.
  • the layered structure composed of the developing material can be arranged on the inner or outer layer of the layered structure composed of the polymer material, and the layered structure composed of the developing material and the layered structure composed of the polymer material can be one or more layers, so that the developing material is formed into The layer structure and the layer structure composed of polymer materials are spaced apart in various arrangements.
  • the material of the second coil 300 includes a developing material and a polymer material. It can also be understood that the material of the second coil 300 is a developing material and a polymer material that are formed by blending and extrusion molding.
  • the developing material and the polymer material can be mixed according to a certain ratio.
  • the developing material can be iodine-based contrast agent, barium sulfate, tantalum powder, etc.
  • the second coil 300 is wound with a degradable wire to form a spiral coil structure, and the ratio of the coil pitch of the second coil 300 to the diameter of the degradable wire is between 1:1 and Between 4:1, for example, the ratio of the coil pitch of the second coil 300 to the diameter of the degradable silk thread is 1:1, 2:1, 3:1, 4:1, etc.
  • the second coil 300 is wound with a non-degradable wire to form a spiral coil structure, and the ratio of the coil pitch of the second coil 300 to the diameter of the non-degradable wire is between 2:1 and 8:1,
  • the ratio of the coil pitch of the second coil 300 to the diameter of the non-degradable wire is 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, etc.
  • the second coil 300 is composed of a developing material and a polymer material, and the mass ratio of the developing material to the polymer material in the second coil 300 is between 1:2 and 4:1, as described in the third coil 300 .
  • the mass ratio of the developing material to the polymer material in the secondary coil 300 is 1:2, 1:1, 2:1, 3:1, 4:1, etc.
  • the mass ratio of the developing material to the polymer material that is, the material suitable for the second coil 300 includes a layer structure formed by the developing material and a layer structure formed by the polymer material, and is also suitable for the second coil 300 .
  • the material is a developing material and a polymer material that are blended and extruded.
  • This application also provides a method for preparing a occlusion implant, which includes the following steps: dissolving degradable polymers in a solvent to prepare a homogeneous solution, using electrospinning to prepare a spinning film, and stretching the spinning film The film forms an electrospun yarn, and the first coil 100 is woven using the electrospun yarn;
  • the first coil 100 and the second coil 300 are shaped, and an anti-unrotation component 200 is connected to the first coil 100 and/or the second coil 300 .
  • the first coil 100 is knitted by a knitting process, and the knitting material includes a first wire.
  • the surface of the first coil 100 formed by using the first wire combined with the knitting process has a rough texture and structure.
  • the rough texture and structure can accelerate the speed of thrombosis, have good thrombogenic effect, quickly promote thrombosis in the short term, effectively reduce the packing density required in arterial fistulas, aneurysms and other locations, and improve the blocking efficiency. Reduce the amount of blocking implants and reduce the high pressure on the blood vessel wall or tumor wall during the operation.
  • the rough texture and structure will produce a porous structure.
  • the porous structure can support the growth and adhesion of cells and can be used as a cell growth scaffold in the medium and long term. , accelerate the endothelialization speed and promote lesion healing, which can effectively solve the risk of blood vessel or aneurysm recanalization.
  • the first silk material is prepared by the following steps: dissolving the degradable polymer in a solvent to prepare a homogeneous solution, using a collection device to perform a spinning operation to obtain the first silk film, and using the The first silk material is made from electrospun films.
  • various process parameters during the preparation process can be defined to obtain the expected first wire material.
  • the weight average molecular weight of the degradable polymer can be limited to between 5W and 20W.
  • the weight average molecular weight of the degradable polymer can be limited to 5W, 6W, 7W, 8W, 9W, 10W, 11W, 12W, 13W. , 14W, 15W, 16W, 17W, 18W, 19W or 20W, etc.
  • the solvent may include any one or a combination of dichloromethane, chloroform, acetone, ethyl acetate, dimethylacetamide, dimethyl sulfoxide, and hexafluoroisopropanol.
  • the concentration of the homogeneous solution can be limited to between 2% and 15%.
  • the concentration of the homogeneous solution can be limited to 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%. , 10%, 11%, 12%, 13%, 14% or 15%, etc.
  • the spinning operation can be limited to a spinning voltage of 5kV to 30kV.
  • the spinning voltage conditions during the spinning operation can be limited to 5kV, 6kV, 7kV, 8kV, 9kV, 10kV, 11kV, 12kV, 13kV.
  • the spinning operation can be limited to a bolus speed of 0.005ml/min to 0.05ml/min.
  • the bolus speed during the spinning operation can be limited to 0.005ml/min, 0.01ml/min, 0.015 ml/min, 0.02ml/min, 0.025ml/min, 0.03ml/min, 0.035ml/min, 0.04ml/min, 0.045ml/min or 0.05ml/min, etc.
  • the spinning operation can be limited to a bolus translation speed of 50mm/min to 5000mm/min.
  • the bolus translation speed during the spinning operation can be limited to 50mm/min, 300mm/min, or 500mm/min. , 800mm/min, 1000mm/min, 2000mm/min, 3000mm/min, 4000mm/min or 5000mm/min, etc.
  • the spinning operation can be limited to a temperature condition of 15°C to 35°C.
  • the temperature condition during the spinning operation can be limited to 15°C, 20°C, 25°C, 30°C or 35°C.
  • the spinning operation may be limited to a humidity of 25% to 45%.
  • the humidity during the spinning operation may be limited to 25%, 30%, 35%, 40% or 45%.
  • the thickness of the electrospun film can be limited to between 1 micron and 10 microns.
  • the thickness of the electrospun film can be limited to 1 micron, 2 microns, 3 microns, 4 microns, 5 microns, 6 microns, 7 microns, 8 micron, 9 micron or 10 micron.
  • the fiber diameter of the electrospun film can be limited to between 300nm and 2000nm.
  • the fiber diameter of the electrospun film can be limited to 300nm, 500nm, 800nm, 1000nm, 1300nm, 1500nm, 1800nm or 2000nm.
  • the electrospun film can have one or more layers of structure. When the electrospun film has a multi-layer structure, different layers of the electrospun film can have different fiber diameters.
  • the diameter of the first wire material can be limited to between 0.02mm and 0.1mm.
  • the diameter of the first wire material can be limited to 0.02mm, 0.03mm, 0.04mm, 0.05mm, 0.06mm, 0.07mm, 0.08mm, 0.09mm or 0.1mm.
  • the collection device can be selected as a collection cylinder with a certain rotation speed and diameter size, and with the ability to separate.
  • the rotation speed of the collection cylinder can be between 10-2000rpm, and the diameter size can be between 2-30cm.
  • the collection cylinder can pass through
  • the release capability can be obtained by setting a release coating, laying a release film or release paper, etc.
  • the electrospun film After the electrospun film is formed through the collection tube, the electrospun film can be removed, cut to a suitable size and shape, stretched and twisted using a stretching and twisting device at a certain temperature, and finally prepared into a diameter of
  • the first wire material is 0.02mm to 0.1mm, wherein the temperature can be maintained at 50-100°C during the stretching and twisting process, and the stretching degree can be limited to 200%-1000%, and the twisting degree can be limited to 1-100%. 5 turns/mm.
  • the collection device can also replace the collection tube through a collection cage or yarn collection port. If the collection device is a yarn collection port, then the subsequent stretching and twisting of the electrospun film can be omitted.
  • a suitable mold can be used to mold the above first mold at a setting temperature of 50 to 100°C.
  • the coil 100 or the second coil 300 is shaped, and then placed at a temperature of -20 to 25°C to cool for 5-60 minutes to complete the final shaping.
  • the first coil 100 is woven using a braided material including at least a first wire material and a second wire material, and the first wire material and the second wire material have different degradation rates, which will cause the anti-untwisting wire to Both ends are threaded along the inside of the first coil 100 from the proximal end to the distal direction, the two ends of the anti-untwisting wire are fixed at the distal end 130 of the first coil, and the anti-untwisting wire is used near the first coil.
  • the outside of end 120 forms a ring-shaped structure.
  • the spinning voltage is 12kV
  • the injection speed is 0.015mm/min
  • the injection translation speed is 400mm/min
  • the surface of the collection tube is wrapped with a silicone oil release film for release
  • the diameter of the collection tube is 12mm
  • the rotation speed of the collection tube is 120rpm.
  • the collection distance is 15cm
  • the temperature is 25°C
  • the humidity is 45%
  • the spinning time is 4min
  • the thickness of the electrospun film is about 2 microns
  • the fiber diameter measured by scanning electron microscopy is about 1500nm.
  • the electrospun film was peeled off and stretched by 400% using a stretching and twisting device, and twisted to 2.5 turns/mm to obtain a first polylactic acid filament yarn with a diameter of 0.09mm.
  • PLA polylactic acid
  • second coil 300 platinum-tungsten alloy coil
  • PGA polyglycolic acid
  • a first coil 100 with an outer diameter of 0.45 mm and two unit coil layers 110 is obtained.
  • the first coil 100 is terminated in the mold using molten 8W molecular weight polyparadioxanone (PPDO).
  • PPDO molten 8W molecular weight polyparadioxanone
  • the first coil 100 is wound on a mold with a predetermined shape and shaped at 90° C. for 15 minutes. After cooling to room temperature, the preparation of the first coil 100 is completed.
  • Iohexol powder and poly-L-lactic acid with a weight average molecular weight of 12W are blended, melted, extruded and drawn into uniform fibers with a diameter of about 0.08mm according to a mass ratio of 1.6:1.
  • This fiber was wound into a developable polymer coil with an external pitch of 0.10mm and an external diameter of 0.30mm.
  • the spinning voltage is 19kV
  • the bolus speed is 0.018mm/min
  • the bolus translation speed is 400mm/min
  • the surface of the collection tube is coated with polytetrafluoroethylene for release
  • the diameter of the collection tube is 12mm
  • the rotation speed of the collection tube is 120rpm.
  • the collection distance is 15cm
  • the temperature is 25°C
  • the humidity is 45%
  • the spinning time is 4min
  • the thickness of the electrospun film obtained is about 2 microns
  • the fiber diameter is about 1200nm measured by scanning electron microscope.
  • the thickness of the electrospun film obtained is about 2.5 microns.
  • the fiber diameter measured by scanning electron microscopy is about 650nm.
  • a unit coil layer 110 of the first coil 100 is knitted around the developable polymer coil using a 0.04 mm polydioxanone (PDO) wire that is pressed one by one and the repeating unit spacing is 2 times the wire diameter.
  • PDO polydioxanone
  • the above-mentioned left-handed polylactic acid first filament yarn is pressed one by one and woven three times to form another three unit coil layers 110 in such a manner that the repeating unit spacing is 2 times the wire diameter.
  • a first coil 100 having four unit coil layers 110 with an outer diameter of 0.35 mm is obtained.
  • the first coil 100 is terminated in the mold using molten 5W molecular weight polyparadioxanone (PPDO).
  • PPDO molten 5W molecular weight polyparadioxanone
  • the first coil 100 is wound on a mold with a predetermined shape, and is shaped at 70° C. for 15 minutes. After cooling to room temperature, the preparation of the first coil 100 is completed.
  • the spinning voltage is 19kV
  • the bolus speed is 0.018mm/min
  • the bolus translation speed is 400mm/min
  • the surface of the collection cylinder is wrapped with a silicone oil release film for release
  • the diameter is 12mm
  • the rotation speed is 120rpm
  • the collection distance is 15cm
  • the temperature was 25°C
  • the humidity was 45%
  • the spinning time was 2 minutes.
  • the thickness of the electrospun film was about 1.2 microns, and the fiber diameter was about 1200nm measured by scanning electron microscopy. Then, adjust the collection distance to 10cm, the temperature to 34°C, and the humidity to 40%. Use a 4% solution for spinning for 16 minutes.
  • the thickness of the electrospun film obtained is about 4 microns
  • the fiber diameter is about 650nm as measured by scanning electron microscopy.
  • the electrospun film was peeled off and stretched by 800% using a stretching and twisting device, and twisted to 3 turns/mm to obtain a first polylactic acid filament yarn with a diameter of 0.035 mm.
  • the platinum-tungsten alloy coil (second coil 300) is placed twice and a connecting ring is reserved at one end.
  • PDO polydioxanone
  • the alloy coil is knitted into one unit coil layer 110 of the first coil 100 .
  • a first coil 100 having four unit coil layers 110 with an outer diameter of 0.30-0.40 mm is obtained.
  • the first coil 100 is wound on a mold with a preset shape and shaped at 70°C for 15 minutes, and then cooled to After room temperature, the preparation of the first coil 100 is completed.
  • PPDO molten polydioxanone
  • the spinning voltage is 13kV
  • the bolus speed is 0.015mm/min
  • the bolus translation speed is 400mm/min
  • the surface of the collection cylinder is wrapped with a silicone oil release film for release
  • the diameter is 12mm
  • the rotation speed is 130rpm
  • the collection distance is 15cm
  • the temperature was 25°C
  • the humidity was 45%
  • the spinning time was 4 minutes
  • the thickness of the electrospun film was about 2 microns
  • the fiber diameter was about 1300nm measured by scanning electron microscopy.
  • a 0.04mm polydioxanone (PDO) wire through a platinum-tungsten alloy coil (second coil 300 ) with a wire diameter of 0.03mm, a pitch of 0.09mm, and an outer diameter of 0.20mm twice and reserve a connecting ring at one end.
  • PDO polydioxanone
  • use the above-mentioned first polypropylene caproate filament yarn to knit the other two unit coil layers 110 of the first coil 100 using one pressing and one repeating unit spacing of 2 times the wire diameter to obtain the outer diameter.
  • the first coil 100 has four unit coil layers 110 of 0.35 mm.
  • the first coil 100 is terminated in the mold using molten 5W molecular weight polyparadioxanone (PPDO).
  • PPDO molten 5W molecular weight polyparadioxanone
  • the first coil 100 is wound on a mold with a predetermined shape and shaped at 50° C. for 15 minutes. After cooling to room temperature, the preparation of the first coil 100 is completed.

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Abstract

本申请涉及一种封堵植入物及其制备方法，包括第一线圈（100）和抗解旋部件（200），第一线圈（100）包括至少一层单元线圈层（110），单元线圈层（110）通过至少一种编织材料编织构成，编织材料至少包含第一丝材，抗解旋部件（200）的至少一部分设置在第一线圈（100）的内部。

Description

封堵植入物及其制备方法
相关申请
本申请要求2022年06月30日申请的，申请号为2022107639805，名称为“封堵植入物及其制备方法”的中国专利申请的优先权，在此将其全文引入作为参考。
技术领域
本申请涉及医疗器械技术领域，特别是涉及一种封堵植入物及其制备方法。
背景技术
弹簧圈是一种针对动脉瘘管、动脉瘤的封堵植入物，同时也常用于外科手术中血管意外损伤出血时的血管紧急封闭，弹簧圈的作用机理为减低局部血流速度、促进血栓形成，从而起到封堵的作用。
常用的弹簧圈主要分为裸金属弹簧圈、水凝胶金属弹簧圈与带高分子绒毛的金属弹簧圈。虽然常用的弹簧圈具有成熟且有效的封堵效果，但是由于金属无法降解，所以在动脉瘘管或动脉瘤愈合后，仍然会留在体内形成占位效应，对其他血管或神经的压迫无法缓解。对此，虽然本领域内发展了可降解的弹簧圈，但是，目前具备可降解能力的弹簧圈技术不够成熟，仍旧存在血管或动脉瘤再通的风险。
发明内容
根据本申请的各种实施例，本申请提供了一种封堵植入物及其制备方法。
一种封堵植入物，包括：
第一线圈，所述第一线圈通过编织材料编织构成，所述编织材料至少包含第一丝材，所述第一丝材为通过静电纺丝方式制备而成的电纺纱线；
第二线圈，所述第二线圈设置在所述第一线圈的内部，所述第二线圈包括显影材料和聚合物材料；及
抗解旋部件，所述抗解旋部件与所述第一线圈和所述第二线圈中的至少一者连接。
在其中一个实施例中，所述第一线圈的近端和远端中的至少一端封闭。
在其中一个实施例中，所述编织材料至少包含第一丝材和第二丝材，所述第一丝材和所述第二丝材的降解速率不同。
在其中一个实施例中，所述第一丝材的材料选自聚左旋乳酸和聚已酸丙酯中的至少一者，所述第二丝材的材料选自聚二氧六环酮、消旋聚乳酸和聚羟基乙酸中的至少一者。
在其中一个实施例中，所述抗解旋部件的至少一部分设置在所述第二线圈的内部。
在其中一个实施例中，所述抗解旋部件包括抗解旋段和连接段，所述抗解旋段处于所 述第二线圈的内部，所述连接段位于所述第二线圈的近端的外部。
在其中一个实施例中，所述抗解旋部件的材料为可降解材料。
在其中一个实施例中，所述抗解旋部件的材料选自聚二氧六环酮、消旋聚乳酸、聚羟基乙酸、聚左旋乳酸、聚羟基乙酸、聚乳酸共聚物、聚已酸丙酯和聚对二氧环已酮中的至少一者。
在其中一个实施例中，所述第二线圈中的显影材料与聚合物材料的质量比约在1：2至4：1之间。
在其中一个实施例中，所述第二线圈中的聚合物材料包括可降解丝线，所述可降解丝线卷绕成螺旋线圈，且所述可降解丝线的线圈螺距与所述可降解丝线的直径的比值在1：1至4：1之间。
在其中一个实施例中，所述第二线圈中的聚合物材料包括不可降解丝线，所述不可降解丝线卷绕成螺旋线圈，且所述不可降解丝线的线圈螺距与所述不可降解丝线的直径的比值在2：1至8：1之间。
一种封堵植入物的制备方法，包括如下步骤：
将可降解高分子溶解在溶剂中制备均质溶液，利用静电纺丝方式制备纺丝薄膜，拉伸所述纺丝薄膜形成电纺纱线，利用所述电纺纱线编织第一线圈；
利用显影材料和聚合物材料制备第二线圈，将所述第二线圈设置在所述第一线圈的内部；及
对所述第一线圈和所述第二线圈进行定型处理，并在所述第一线圈和所述第二线圈中的至少一者上连接抗解旋部件。
在其中一个实施例中，包括如下步骤：
采用热熔封闭的方式对所述第一线圈的近端和远端中的至少一端进行封闭处理。
在其中一个实施例中，包括如下步骤：
将可降解材料在热熔后施加在所述第一线圈的近端和远端中的至少一端，然后通过可降解材料的冷却对所述第一线圈的近端和远端中的至少一端进行封闭处理。
在其中一个实施例中，包括如下步骤：
将所述第一线圈的近端和远端中的至少一端放置在模具中，将聚对二氧环已酮、消旋聚乳酸、聚羟基乙酸、聚左旋乳酸、聚羟基乙酸、聚乳酸共聚物、聚已酸丙酯和聚二氧六环酮中的至少一者在所述模具中热熔，通过热熔后的冷却对所述第一线圈的近端和远端中的至少一端进行封闭处理。
本申请的一个或多个实施例的细节在下面的附图和描述中提出，本申请的其他特征、 目的和优点将从说明书、附图以及权利要求书中变得明显。
附图说明
为了更清楚地说明本申请实施例或传统技术中的技术方案，下面将对实施例或传统技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据公开的附图获得其他的附图。
图1为本申请一些实施例提供的封堵植入物的第一部分截面示意图；
图2为本申请一些实施例提供的封堵植入物的第二部分截面示意图。
附图标号：
100、第一线圈；200、抗解旋部件；300、第二线圈；
110、单元线圈层；120、第一线圈的近端；130、第一线圈的远端；
210、抗解旋段；220、连接段。
具体实施方式
下面将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
为使本申请的上述目的、特征和优点能够更加明显易懂，下面结合附图对本申请的实施方式做详细的说明。在下面的描述中阐述了很多细节以便于充分理解本申请。但是本申请能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本申请内涵的情况下做类似改进，因此本申请不受下面公开的实施例的限制。
为了更加清楚地描述封堵植入物的结构，此处限定术语“远端”表示手术操作过程中远离操作人员的一端，“近端”表示手术操作过程中靠近操作人员的一端。除非另有定义，本申请所使用的所有的技术和科学术语与属于本申请的技术领域的技术人员通常理解的含义相同。本申请在说明书中所使用的术语只是为了描述实施例的目的，不是旨在于限制本申请。
参阅图1和图2，本申请一实施例提供了一种封堵植入物，所述封堵植入物包括第一线圈100、第二线圈300和抗解旋部件200，所述第一线圈100通过编织材料编织构成，所述编织材料至少包含第一丝材，所述第一丝材为通过静电纺丝方式制备而成的电纺纱线，所述第二线圈300设置在所述第一线圈100的内部，所述第二线圈包括显影材料和聚合物材料，所述抗解旋部件与所述第一线圈和所述第二线圈中的至少一者连接。封堵植入物包 括用于封堵动脉瘘管、动脉瘤的物质，例如医用弹簧圈、封堵网等结构，如封堵植入物为医用弹簧圈时，封堵植入物的第一线圈100、第二线圈300便是沿着螺旋形状构成的螺旋线圈结构，如封堵植入物为医用封堵网时，封堵植入物的第一线圈100、第二线圈300也可以是沿着网状结构构成的网状线圈或沿着其他轨迹或弧面构成的线圈结构，本领域技术人员可以根据实际需求选择设置封堵植入物的结构，在此不做限定。
所述第一线圈100可以包括至少一层单元线圈层110，而所述单元线圈层110通过至少一种编织材料编织构成，例如，所述第一线圈100可以通过多层单元线圈层110套装而成，因为每层单元线圈层110均通过编织材料构成，因此第一线圈100也相当于通过编织材料构成。第一线圈100和第二线圈300的内部可以理解为第一线圈100和第二线圈300的内圈以及线圈之间的间隙等结构，在此不做限定。
封堵植入物的第一线圈100为封堵植入物发挥封堵功能的主要部分，第一线圈100通过编织工艺编织构成，并且编织材料中包含了第一丝材，利用第一丝材结合编织工艺构成的第一线圈100的表面具有粗糙的纹理与结构，粗糙的纹理与结构能够加快血栓形成的速度、具备良好的致栓效果，在短期内迅速促进血栓形成，有效地降低动脉瘘管、动脉瘤等位置内所需要的填塞密度，提高封堵效率，减少封堵植入物的用量，降低术中较高的血管壁或瘤壁压力，而且，粗糙的纹理与结构会产生多孔结构，多孔结构能够支持细胞的生长攀附，中长期可作为细胞生长支架，加快内皮化速度，促进病灶愈合，这均能够有效地解决血管或动脉瘤再通的风险。
需要说明的是，编织构成第一线圈100的编织工艺可以为任意编织方式，例如编织工艺可以采用一股压一股的双股编织，也可以采用一股压二股的三股编织，二股压二股的四股编织、一股压三股的四股编织以及其他常见的编织方式，其中，编织构成的第一线圈100中，编织重复单元之间的间距可以为0.5倍至10倍的丝材直径，本领域技术人员可以根据需求选择合适的编织方式，进而构成粗糙的纹理与结构，在此不做限定。
所述第一线圈的近端120或所述第一线圈的远端130可以进行封闭处理，当所述第一线圈的近端120和所述第一线圈的远端130中至少一端被封闭处理后，就能够形成对血管的封堵效果，封闭处理的方式可以采用多种形式，例如采用热熔封闭的方式将所述第一线圈的近端120和所述第一线圈的远端130进行封闭处理，热熔封闭时可以利用聚对二氧环已酮(PPDO)、消旋聚乳酸(PDLLA)、聚羟基乙酸(PGA)、聚左旋乳酸(PLLA)、聚羟基乙酸/聚乳酸共聚物(PLGA)、聚已酸丙酯(PCL)和聚二氧六环酮(PDO)等可降解材料在模具进行热熔处理，然后通过冷却对所述第一线圈的近端120和所述第一线圈的远端130进行封闭，这种封闭处理方式还能够提高所述第一线圈的近端120或所述第一线圈的远端130的 柔软度，形成较为柔软的端部结构，使所述第一线圈的近端120或所述第一线圈的远端130接触血管壁的时候不会损伤或刺破血管。
用于编织第一线圈100的编制材料除了包含第一丝材以外，还可以通过将第一丝材与其他第二丝材结合的方式进行编织，例如在其中一个实施例中，所述编织材料至少包含第一丝材和第二丝材两种材料，其中，所述第一丝材和所述第二丝材的材料可以分别选择为降解速率不同的可降解材料，因此，第一线圈100具备可降解的效果，能够降低长期占位效应，而且，所述编织材料中第一丝材和第二丝材具有不同的降解速率，能够使第一线圈100在体内形成接力降解的效果，即编织材料中第一丝材和第二丝材分别以不同的降解速率接力降解，者能够在缩短患者康复周期的同时降低封堵失效、血流再通的风险。
第一丝材和第二丝材具有不同的降解速率，例如在其中一个实施例中，所述第一丝材的材料可以包括降解速率在2至4年的可降解材料，所述第二丝材的材料可以包括降解速率在1.5年内的可降解材料，因此，当封堵植入物在体内经过1.5年内的时间，编制丝材可以首先降解，此时第一丝材还没有完全降解，第二丝材的降解能够降低占位效应，而第一丝材的存留能够继续发挥封堵功能，降低封堵失效、血流再通的风险，因此，通过两种不同的降解速率，可以平衡占位效应的再通风险的问题，得到良好的治疗效果。
在其中一个实施例中，所述第一丝材的材料包括聚左旋乳酸和聚已酸丙酯中的任意一种或组合，所述第二丝材的材料包括聚二氧六环酮、消旋聚乳酸和聚羟基乙酸中的任意一种或组合，除此之外，本领域技术人员也可以根据需求选择其他的材料，在此不做限定。
抗解旋部件200能够避免第一线圈100在外力作用下被拉直，达到抗解旋的作用，抗解旋部件200可以采用任意结构形式，例如结合图1和图2所示，在其中一个实施例中，所述抗解旋部件200包括抗解旋段210和连接段220，所述抗解旋段210处于所述第一线圈100的内部，所述连接段220位于所述第一线圈的近端120的外部，其中，抗解旋部件200可以通过一股或两股以上的抗解旋丝线构成，例如将一股抗解旋丝线进行对折，该股抗解旋丝线的两端合并到一起，可以称之为抗解旋丝线的远端，抗解旋丝线可见于图1中的右侧位置，此时，该股抗解旋丝线会在图2中的左侧形成一个环形结构，可以称之为抗解旋丝线的近端，可以将抗解旋丝线的远端沿着第一线圈100的内部由近端向远端方向穿设，将抗解旋丝线的远端固定在第一线圈的远端130，并利用抗解旋丝线的近端在第一线圈的近端120的外部形成环形结构，环形结构的长度可以在0.5-3mm之间，位于第一线圈100的内部的部分可以构成抗解旋部件200的抗解旋段210，外露的环形结构可以构成抗解旋部件200的连接段220。
所述抗解旋部件200的材料可以采用可降解材料或不可降解材料，例如在其中一个实 施例中，所述抗解旋部件200的材料可以包括可降解的聚二氧六环酮、消旋聚乳酸、聚羟基乙酸、聚左旋乳酸、聚羟基乙酸、聚乳酸共聚物、聚已酸丙酯、聚对二氧环已酮中的任意一种或组合。
在其中一个实施例中，所述抗解旋部件可以与所述第一线圈连接、也可以与所述第二线圈连接，其中，抗解旋部件的连接可以为可拆卸连接或非可拆卸连接，例如采用固定连接形式或卡扣、绑接等连接形式，在此不做限定，而且借助于第一线圈100和第二线圈300之间的装配关系，所述抗解旋部件200也可以将至少一部分可以设置在所述第一线圈100的内部。
第二线圈300的材料可以根据功能需求进行选择，例如在其中一个实施例中，所述第二线圈300的材料为可降解材料，或者，所述第二线圈300的材料为不可降解材料，或者，所述第二线圈300的材料包括显影材料和聚合物材料，聚合物可以为可降解材料或不可降解材料。
需要说明的是，所述第二线圈300的材料包括显影材料和聚合物材料，可理解为所述第二线圈300的材料包括了通过显影材料构成的层面结构以及通过聚合物材料构成层面结构，例如显影材料构成的层面结构可以设置在聚合物材料构成层面结构的内层或外层，并且，显影材料构成的层面结构以及聚合物材料构成层面结构可以为一层或多层，使显影材料构成的层面结构以及聚合物材料构成层面结构之间以多种排布方式间隔设置。
除此之外，所述第二线圈300的材料包括显影材料和聚合物材料，也可理解为所述第二线圈300的材料为显影材料以及聚合物材料采用共混挤出成型的方式构成，显影材料以及聚合物材料能够按照一定的比例配比而成，其中，显影材料可以采用如碘系造影剂、硫酸钡、钽粉等。
例如在其中一个实施例中，所述第二线圈300通过可降解丝线卷绕构成螺旋线圈结构，且所述第二线圈300的线圈螺距与所述可降解丝线的直径的比值在1：1至4：1之间，如所述第二线圈300的线圈螺距与所述可降解丝线的直径的比值为1：1、2：1、3：1、4：1等。或者，所述第二线圈300通过不可降解丝线卷绕构成螺旋线圈结构，且所述第二线圈300的线圈螺距与所述不可降解丝线的直径的比值在2：1至8：1之间，如所述第二线圈300的线圈螺距与所述不可降解丝线的直径的比值为2：1、3：1、4：1、5：1、6：1、7：1、8：1等。或者，所述第二线圈300通过显影材料和聚合物材料构成，且所述第二线圈300中的显影材料与聚合物材料的质量比在1：2至4：1之间，如所述第二线圈300中的显影材料与聚合物材料的质量比为1：2、1：1、2：1、3：1、4：1等，本领域技术人员可以根据需求设置，在此不做限定。
其中，显影材料与聚合物材料的质量比即适用于所述第二线圈300的材料包括了通过显影材料构成的层面结构以及通过聚合物材料构成层面结构，也适用于所述第二线圈300的材料为显影材料以及聚合物材料采用共混挤出成型的方式构成。
本申请还提供了一种封堵植入物的制备方法，包括如下步骤：将可降解高分子溶解在溶剂中制备均质溶液，利用静电纺丝方式制备纺丝薄膜，拉伸所述纺丝薄膜形成电纺纱线，利用所述电纺纱线编织第一线圈100；
利用显影材料和聚合物材料制备第二线圈300，将所述第二线圈300设置在所述第一线圈100的内部；
对所述第一线圈100和所述第二线圈300进行定型处理，并在所述第一线圈100和/或所述第二线圈300上连接抗解旋部件200。
在其中一个实施例中，第一线圈100通过编织工艺编织构成，并且编织材料中包含了第一丝材，利用第一丝材结合编织工艺构成的第一线圈100的表面具有粗糙的纹理与结构，粗糙的纹理与结构能够加快血栓形成的速度、具备良好的致栓效果，在短期内迅速促进血栓形成，有效地降低动脉瘘管、动脉瘤等位置内所需要的填塞密度，提高封堵效率，减少封堵植入物的用量，降低术中较高的血管壁或瘤壁压力，而且，粗糙的纹理与结构会产生多孔结构，多孔结构能够支持细胞的生长攀附，中长期可作为细胞生长支架，加快内皮化速度，促进病灶愈合，这均能够有效地解决血管或动脉瘤再通的风险。
在其中一个实施例中，所述第一丝材通过如下步骤制备：将可降解高分子溶解在溶剂中制备均质溶液，利用收集装置进行纺丝操作，得到第一丝材薄膜，利用所述电纺丝薄膜制作第一丝材。通过上述步骤制备第一丝材时，可以限定制备过程中的各种工艺参数，以能够获得预期的第一丝材。
例如，所述可降解高分子的重均分子量可以限定在5W至20W之间，例如可降解高分子的重均分子量可以限定为5W、6W、7W、8W、9W、10W、11W、12W、13W、14W、15W、16W、17W、18W、19W或20W等。
所述溶剂可以限定包括二氯甲烷、三氯甲烷、丙酮、乙酸乙酯、二甲基乙酰胺、二甲基亚砜、六氟异丙醇中的任意一种或组合。
所述均质溶液的浓度可以限定在2％至15％之间，例如均质溶液的浓度可以限定为2％、3％、4％、5％、6％、7％、8％、9％、10％、11％、12％、13％、14％或15％等。所述纺丝操作可以限定在5kV至30kV的纺丝电压条件下进行，例如纺丝操作过程中的纺丝电压条件可以限定为5kV、6kV、7kV、8kV、9kV、10kV、11kV、12kV、13kV、14kV、15kV、16kV、17kV、18kV、19kV、20kV、21kV、22kV、23kV、24kV、25kV、26kV、27kV、 28kV、29kV或30kV。
所述纺丝操作可以限定在0.005ml/min至0.05ml/min的推注速度条件下进行，例如纺丝操作过程中的推注速度条件可以限定为0.005ml/min、0.01ml/min、0.015ml/min、0.02ml/min、0.025ml/min、0.03ml/min、0.035ml/min、0.04ml/min、0.045ml/min或0.05ml/min等。
所述纺丝操作可以限定在50mm/min至5000mm/min的推注平移速度条件下进行，例如纺丝操作过程中的推注平移速度条件可以限定为50mm/min、300mm/min、500mm/min、800mm/min、1000mm/min、2000mm/min、3000mm/min、4000mm/min或5000mm/min等。
所述纺丝操作可以限定在15℃至35℃的温度条件下进行，例如纺丝操作过程中的温度条件可以限定为15℃、20℃、25℃、30℃或35℃。
所述纺丝操作可以限定在25％至45％的湿度条件下进行，例如纺丝操作过程中的湿度条件可以限定为25％、30％、35％、40％或45％。
所述电纺丝薄膜的厚度可以限定在1微米至10微米之间，例如电纺丝薄膜的厚度可以限定为1微米、2微米、3微米、4微米、5微米、6微米、7微米、8微米、9微米或10微米。
所述电纺丝薄膜的纤维直径可以限定在300nm至2000nm之间，例如电纺丝薄膜的纤维直径可以限定为300nm、500nm、800nm、1000nm、1300nm、1500nm、1800nm或2000nm。同时，电纺丝薄膜可以具有一层或多层结构，当电纺丝薄膜具有多层结构时，电纺丝薄膜的不同层可以具有不同的纤维直径。
所述第一丝材的直径可以限定在0.02mm至0.1mm之间，例如第一丝材的直径可以限定为0.02mm、0.03mm、0.04mm、0.05mm、0.06mm、0.07mm、0.08mm、0.09mm或0.1mm。
收集装置可以选择为具有一定转速和直径尺寸，且具有离型能力的收集筒，例如收集筒的转速可以在10-2000rpm之间、直径尺寸可以在2-30cm之间，根据需求收集筒可以通过设置离型涂层、铺设离型膜或离型纸等方式获得离型能力。通过收集筒形成电纺丝薄膜后，可以将电纺丝薄膜取下，剪裁至合适的尺寸和形状，在一定温度下使用拉伸加捻设备将其拉伸、加捻，最终制备成直径为0.02mm至0.1mm的第一丝材，其中，拉伸加捻过程中可以保持温度在50-100℃，而且，拉伸程度可以限定在200％-1000％，加捻程度可以限定在1-5圈/mm。
除此之外，收集装置也可以通过收集笼或纱线收集口替代收集筒，此时收集装置若为纱线收集口，那么便可以省略掉后续电纺丝薄膜的拉伸与加捻。
完成上述制备工序后，可以使用适配的模具，在50至100℃的定型温度下将上述第一 线圈100或第二线圈300定型，然后再放置到-20至25℃的温度下冷却5-60min完成最终定型。
在其中一个实施例中，利用至少包含第一丝材和第二丝材的编织材料编织构成第一线圈100，且第一丝材和第二丝材的降解速率不同，将抗解旋丝线的两端沿着第一线圈100的内部由近端向远端方向穿设，将抗解旋丝线的两端固定在第一线圈的远端130，并利用抗解旋丝线在第一线圈的近端120的外部形成环形结构。
实施例1：
将12W重均分子量聚左旋乳酸溶解于六氟异丙醇中，配置成9％质量浓度的均质溶液。使用此均质溶液根据如下工艺参数进行第一丝材：
纺丝电压为12kV，推注速度为0.015mm/min，推注平移速度为400mm/min，收集筒表面包裹硅油离型膜进行离型，收集筒的直径为12mm，收集筒的转速为120rpm，收集距离为15cm，温度为25℃，湿度为45％，纺丝时间为4min，电纺丝薄膜厚度约为2微米，纤维直径经扫描电镜测量约为1500nm。
将负载有电纺丝薄膜的硅油离型膜从收集筒上取下并剪裁成2cm长条状。将电纺丝薄膜剥离并使用拉伸加捻装置将其拉伸400％，加捻至2.5圈/mm，获得直径为0.09mm的聚乳酸第一丝材纱线。
将0.07mm的聚乳酸(PLA)丝材穿越丝径0.03mm，螺距0.09mm，外径0.30mm的铂钨合金线圈(第二线圈300)两次并在一端预留连接环。使用0.06mm的聚羟基乙酸(PGA)丝材使用一压一，重复单元间距为2倍线径的方式围绕铂钨合金线圈编织成第一线圈100的一个单元线圈层110。在此基础上，使用上述聚左旋乳酸第一丝材纱线使用一压一，重复单元间距为2倍线径的方式编织成第一线圈100的另一个单元线圈层110。获得外径为0.45mm，且具有两层单元线圈层110的第一线圈100。
使用熔融的8W分子量聚对二氧环已酮(PPDO)在模具内完成第一线圈100的封端。将第一线圈100绕制在预先设定形状的模具上进行90℃定型15min，冷却至室温后完成第一线圈100的制备。
实施例2：
将碘海醇粉末与12W重均分子量的聚左旋乳酸按照质量比1.6：1的配比进行共混熔融挤出并拉制成为直径约0.08mm的均匀纤维。将此纤维卷绕成外螺距0.10mm，外径0.30mm的可显影聚合物线圈。
将12W重均分子量聚左旋乳酸溶解于六氟异丙醇中，配置成9％与4％两种不同质量 浓度的均质溶液，使用9％的均质溶液根据如下工艺参数进行第一丝材：
纺丝电压为19kV，推注速度为0.018mm/min，推注平移速度为400mm/min，收集筒表面涂覆聚四氟乙烯进行离型，收集筒的直径为12mm，收集筒的转速为120rpm，收集距离为15cm，温度为25℃，湿度为45％，纺丝时间为4min，获得电纺丝薄膜厚度约为2微米，纤维直径经扫描电镜测量约为1200nm。紧接着，调整收集距离为10cm，温度为34℃，湿度为40％，使用4％的均质溶液进行纺丝8min，获得电纺丝薄膜厚度约为2.5微米，纤维直径经扫描电镜测量约为650nm。
将电纺丝薄膜从收集筒上取下并剪裁成2cm长条状，使用拉伸加捻装置将其拉伸800％，加捻至4圈/mm，获得直径为0.035mm的左旋聚乳酸第一丝材纱线。
将0.04mm的聚二氧六环酮(PDO)丝材穿越可显影聚合物线圈(第二线圈300)两次并在一端预留连接环。使用0.04mm的聚二氧六环酮(PDO)丝材使用一压一，重复单元间距为2倍线径的方式围绕可显影聚合物线圈编织成第一线圈100的一个单元线圈层110。在此基础上，使用上述左旋聚乳酸第一丝材纱线使用一压一，重复单元间距为2倍线径的方式编织三次形成另外三层单元线圈层110。获得外径为0.35mm的具有四层单元线圈层110的第一线圈100。
使用熔融的5W分子量聚对二氧环已酮(PPDO)在模具内完成第一线圈100的封端。将第一线圈100绕制在预先设定形状的模具上进行70℃定型15min，冷却至室温后完成第一线圈100的制备。
实施例3：
将12W重均分子量聚左旋乳酸溶解于六氟异丙醇中，配置成9％与4％两种不同质量浓度的均质溶液。使用9％的溶液根据如下工艺参数进行第一丝材：
纺丝电压为19kV，推注速度为0.018mm/min，推注平移速度为400mm/min，收集筒表面包裹硅油离型膜进行离型，直径为12mm，转速为120rpm，收集距离为15cm，温度为25℃，湿度为45％，纺丝时间为2min，获得电纺丝薄膜厚度约为1.2微米，纤维直径经扫描电镜测量约为1200nm。紧接着，调整收集距离为10cm，温度为34℃，湿度为40％，使用4％的溶液进行纺丝16min，获得电纺丝薄膜厚度约为4微米，纤维直径经扫描电镜测量约为650nm。
将负载有电纺丝薄膜的硅油离型膜从收集筒上取下并剪裁成2cm长条状。将电纺丝薄膜剥离并使用拉伸加捻装置将其拉伸800％，加捻至3圈/mm，获得直径为0.035mm的聚乳酸第一丝材纱线。
将0.04mm的聚二氧六环酮(PDO)丝材穿越丝径0.03mm，螺距0.09mm，外径0.20mm 的铂钨合金线圈(第二线圈300)两次并在一端预留连接环。使用一根0.04mm的聚二氧六环酮(PDO)丝材与两根聚左旋聚乳酸第一丝材纱线使用一压二，重复单元间距为3-5倍线径的方式围绕铂钨合金线圈编织成第一线圈100的一个单元线圈层110。在此基础上，使用一根上述聚二氧六环酮(PDO)丝材与一根聚左旋乳酸第一丝材纱线使用一压一，重复单元间距为2倍线径的方式编织三次形成第一线圈100的另外三个单元线圈层110。获得外径为0.30-0.40mm的具有四层单元线圈层110的第一线圈100。
使用熔融的5W分子量聚对二氧环已酮(PPDO)在模具内完成第一线圈100的封端，将第一线圈100绕制在预先设定形状的模具上进行70℃定型15min，冷却至室温后完成第一线圈100的制备。
实施例4：
将8W重均分子量聚已酸丙酯溶解于六氟异丙醇中，配置成9％的均质溶液。使用此溶液根据如下工艺参数进行第一丝材：
纺丝电压为13kV，推注速度为0.015mm/min，推注平移速度为400mm/min，收集筒表面包裹硅油离型膜进行离型，直径为12mm，转速为130rpm，收集距离为15cm，温度为25℃，湿度为45％，纺丝时间为4min，电纺丝薄膜厚度约为2微米，纤维直径经扫描电镜测量约为1300nm。
将负载有电纺丝薄膜的硅油离型膜从收集筒上取下并剪裁成2cm长条状，将电纺丝薄膜剥离并使用拉伸加捻装置将其拉伸1000％，加捻至5圈/mm，获得直径为0.035mm的聚已酸丙酯第一丝材纱线。
将0.04mm的聚二氧六环酮(PDO)丝材穿越丝径0.03mm，螺距0.09mm，外径0.20mm的铂钨合金线圈(第二线圈300)两次并在一端预留连接环。使用0.04mm的聚二氧六环酮(PDO)丝材使用一压一，重复单元间距为2倍线径的方式围绕铂钨合金线圈编织两次成第一线圈100的两个单元线圈层110。在此基础上，使用上述聚已酸丙酯第一丝材纱线使用一压一，重复单元间距为2倍线径的方式编织第一线圈100的另外两个单元线圈层110，获得外径为0.35mm的具有四层单元线圈层110的第一线圈100。
使用熔融的5W分子量聚对二氧环已酮(PPDO)在模具内完成第一线圈100的封端。将第一线圈100绕制在预先设定形状的模具上进行50℃定型15min，冷却至室温后完成第一线圈100的制备。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为详细，但并不能因此而理解为对发明专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请专利的保护范围应以所附权利要求为准。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为详细，但并不能因此而理解为对申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请专利的保护范围应以所附权利要求为准。

Claims (15)

  1. 一种封堵植入物，其特征在于，包括：
    第一线圈，所述第一线圈通过编织材料编织构成，所述编织材料至少包含第一丝材，所述第一丝材为通过静电纺丝方式制备而成的电纺纱线；
    第二线圈，所述第二线圈设置在所述第一线圈的内部，所述第二线圈包括显影材料和聚合物材料；及
    抗解旋部件，所述抗解旋部件与所述第一线圈和所述第二线圈中的至少一者连接。
  2. 根据权利要求1所述的封堵植入物，其特征在于，所述第一线圈的近端和远端中的至少一端封闭。
  3. 根据权利要求1所述的封堵植入物，其特征在于，所述编织材料至少包含第一丝材和第二丝材，所述第一丝材和所述第二丝材的降解速率不同。
  4. 根据权利要求3所述的封堵植入物，其特征在于，所述第一丝材的材料选自聚左旋乳酸和聚已酸丙酯中的至少一者，所述第二丝材的材料选自聚二氧六环酮、消旋聚乳酸和聚羟基乙酸中的至少一者。
  5. 根据权利要求1所述的封堵植入物，其特征在于，所述抗解旋部件的至少一部分设置在所述第二线圈的内部。
  6. 根据权利要求5所述的封堵植入物，其特征在于，所述抗解旋部件包括抗解旋段和连接段，所述抗解旋段处于所述第二线圈的内部，所述连接段位于所述第二线圈的近端的外部。
  7. 根据权利要求1所述的封堵植入物，其特征在于，所述抗解旋部件的材料为可降解材料。
  8. 根据权利要求7所述的封堵植入物，其特征在于，所述抗解旋部件的材料选自聚二氧六环酮、消旋聚乳酸、聚羟基乙酸、聚左旋乳酸、聚羟基乙酸、聚乳酸共聚物、聚已酸丙酯、聚对二氧环已酮中的至少一者。
  9. 根据权利要求1所述的封堵植入物，其特征在于，所述第二线圈中的显影材料与聚合物材料的质量比约在1：2至4：1之间。
  10. 根据权利要求1所述的封堵植入物，其特征在于，所述第二线圈中的聚合物材料包括可降解丝线，所述可降解丝线卷绕成螺旋线圈，且所述可降解丝线的线圈螺距与所述可降解丝线的直径的比值在1：1至4：1之间。
  11. 根据权利要求1所述的封堵植入物，其特征在于，所述第二线圈中的聚合物材料包括不可降解丝线，所述不可降解丝线卷绕成螺旋线圈，且所述不可降解丝线的线圈螺距 与所述不可降解丝线的直径的比值在2：1至8：1之间。
  12. 一种封堵植入物的制备方法，其特征在于，包括如下步骤：
    将可降解高分子溶解在溶剂中制备均质溶液，利用静电纺丝方式制备纺丝薄膜，拉伸所述纺丝薄膜形成电纺纱线，利用所述电纺纱线编织第一线圈；
    利用显影材料和聚合物材料制备第二线圈，将所述第二线圈设置在所述第一线圈的内部；及
    对所述第一线圈和所述第二线圈进行定型处理，并在所述第一线圈和所述第二线圈中的至少一者上连接抗解旋部件。
  13. 根据权利要求12所述的制备方法，其特征在于，包括如下步骤：
    采用热熔封闭的方式对所述第一线圈的近端和远端中的至少一端进行封闭处理。
  14. 根据权利要求13所述的制备方法，其特征在于，包括如下步骤：
    将可降解材料在热熔后施加在所述第一线圈的近端和远端中的至少一端，然后通过可降解材料的冷却对所述第一线圈的近端和远端中的至少一端进行封闭处理。
  15. 根据权利要求14所述的制备方法，其特征在于，包括如下步骤：
    将所述第一线圈的近端和远端中的至少一端放置在模具中，将聚对二氧环已酮、消旋聚乳酸、聚羟基乙酸、聚左旋乳酸、聚羟基乙酸、聚乳酸共聚物、聚已酸丙酯和聚二氧六环酮中的至少一者在所述模具中热熔，通过热熔后的冷却对所述第一线圈的近端和远端中的至少一端进行封闭处理。
PCT/CN2023/099317 2022-06-30 2023-06-09 封堵植入物及其制备方法 WO2024001718A1 (zh)

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