WO2023116498A1 - 一种栓塞物 - Google Patents

一种栓塞物 Download PDF

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Publication number
WO2023116498A1
WO2023116498A1 PCT/CN2022/138570 CN2022138570W WO2023116498A1 WO 2023116498 A1 WO2023116498 A1 WO 2023116498A1 CN 2022138570 W CN2022138570 W CN 2022138570W WO 2023116498 A1 WO2023116498 A1 WO 2023116498A1
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WIPO (PCT)
Prior art keywords
embolism
plug body
developing
plug
developing element
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PCT/CN2022/138570
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English (en)
French (fr)
Inventor
张朔
杨瑞
郭远益
钱少君
余画
Original Assignee
神遁医疗科技(上海)有限公司
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Publication of WO2023116498A1 publication Critical patent/WO2023116498A1/zh

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    • 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
    • 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
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/148—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00004—(bio)absorbable, (bio)resorbable, resorptive
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00867—Material properties shape memory effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B2017/00831—Material properties
    • A61B2017/00902—Material properties transparent or translucent
    • A61B2017/00915—Material properties transparent or translucent for radioactive radiation
    • A61B2017/0092—Material properties transparent or translucent for radioactive radiation for X-rays

Definitions

  • the invention relates to the technical field of medical devices, in particular to an embolism.
  • Intracranial aneurysm is a common cerebrovascular disease, which is caused by a variety of factors to destroy the structure of the intracranial artery wall and abnormal bulge of the wall, and is one of the important causes of subarachnoid hemorrhage.
  • coil embolization is a common treatment method.
  • Coil embolization of aneurysms can reduce the impact of blood flow on the aneurysm wall, on the other hand, it can induce thrombus formation and thrombus organization in the aneurysm cavity, and realize the occlusion of the aneurysm.
  • the endothelialization time is about 6 months, so when using these biomodified coil products for interventional treatment of aneurysms, if the volume ratio of polymer materials in the product is relatively low High, when the polymer material is completely degraded, the tumor cavity has not yet fully organized to form fibrous tissue, and there is a risk of aneurysm recanalization due to the decrease in embolism density caused by the degradation of the polymer material. However, if the polymer material in the product The volume ratio is small, and the mass effect cannot be effectively alleviated after the tumor cavity is fully organized.
  • the object of the present invention is to provide an embolism, which is used for implanting into the tumor cavity of the hemangioma to promote thrombus organization in the tumor cavity, avoid recanalization of the aneurysm, and effectively alleviate the mass effect after the tumor cavity is completely occluded.
  • the present invention provides a plug, including a plug body, the plug body is a helical part, and the material of the plug body is polylactic acid-glycolic acid copolymer, and by weight percentage, lactic acid The proportion is 80%-85%, so that the degradation time of the plug body at a predetermined temperature is longer than 6 months.
  • the intrinsic viscosity of the polylactic acid-glycolic acid copolymer is 1.2dL/g-2.0dL/g, and the weight average molecular weight is 200000g/mol-500000g/mol.
  • the plug body is formed by helically winding wires, the breaking strength of the wires is greater than or equal to 200 MPa, the elongation at break is greater than or equal to 10%, and the heat shrinkage rate is less than or equal to 25%.
  • the polylactic acid-glycolic acid copolymer has a crystallinity greater than or equal to 40%.
  • the polylactic acid-glycolic acid copolymer has a glass transition temperature of 50°C to 60°C.
  • the plug body is a tubular component with a first lumen; the plug further includes a developing element, which is disposed in the first lumen and connected to the plug body.
  • the developing element is a metal part made of radiopaque metal; or, the developing element is a composite material part doped with a developing substance in the matrix, wherein the developing substance is iodine contrast agent or sulfuric acid Barium, the matrix is any one or more of polylactic acid, polycaprolactone polyglycolic acid, lactic acid-glycolic acid copolymer, polydioxanone, polyurethane, chitosan and hyaluronic acid .
  • the developing element is a tubular member with a second lumen, and the length of the developing element matches the length of the plug body.
  • the developing element is a spiral component, or the developing element is a tube mesh component.
  • the ratio of the volume of the developing element to the volume of the plug body is less than or equal to 50%.
  • the plug further includes a shaping element, which is disposed in the second lumen, connected to the plug body, and used to keep the plug in a preset shape.
  • a shaping element which is disposed in the second lumen, connected to the plug body, and used to keep the plug in a preset shape.
  • the plug body is a tubular component with a first lumen; the plug also includes a shaping element, the shaping element is arranged in the first lumen and connected with the plug body, and is used To keep the emboli in a predetermined shape.
  • the ratio of the volume of the shaping element to the volume of the plug body is less than or equal to 10%.
  • the embolism of the present invention has the following advantages:
  • the aforementioned embolism includes a plug body, the plug body is a helical part, and the material of the plug body is polylactic acid-glycolic acid copolymer, and in terms of weight percentage, the proportion of lactic acid is 80% to 85%, so that The degradation time of the plug body at a predetermined temperature is greater than 6 months.
  • the predetermined temperature refers to the temperature of the environment inside the human body, and the specific value is about 37°C, for example, 36.8°C-37.2°C.
  • the embolism is used to be implanted in the tumor cavity of the hemangioma, and promotes the thrombusization and organization of the hemangioma, and the degradation rate of the embolism body is relatively suitable, which can match the time of tumor cavity occlusion and tumor neck endothelialization, and will not The degradation is completed before the tumor cavity is fully organized, which can effectively avoid the recanalization of the hemangioma, and can also alleviate or even relieve the mass effect.
  • the intrinsic viscosity of the polylactic acid-glycolic acid copolymer is 1.2dL/g-2.0dL/g, and the weight-average molecular weight is 200000g/mol-500000g/mol.
  • the plug body is helically wound from a wire, and the breaking strength of the wire is greater than or equal to 200MPa, the elongation at break is greater than or equal to 10%, and the heat shrinkage rate is less than or equal to 25%.
  • the plug body can Maintain the stability of the structure at the predetermined temperature and avoid untwisting, that is to say, the embolism can be kept as a helical part in the body, and can effectively fill the tumor cavity and promote thrombusization and organization of the tumor cavity.
  • Fig. 1 is a schematic structural view of an embolism provided by the present invention according to an embodiment.
  • Fig. 2 is a graph showing the relationship between mass/weight average molecular weight loss and time when the plug body of the plug provided by the embodiment of the present invention is degraded at 37°C.
  • Fig. 3 is a scanning electron micrograph of the main body of the embolism provided by the embodiment of the present invention when it degrades at 37°C for 120 days.
  • Fig. 4 is a scanning electron microscope image of the main body of the embolism provided by the embodiment of the present invention when it degrades at 37°C for 270 days.
  • Fig. 5 is a scanning electron micrograph of the main body of the embolism provided by the embodiment of the present invention when it is degraded at 50°C for 14 days.
  • Fig. 6 is a scanning electron micrograph of the main body of the embolism provided by the embodiment of the present invention when it degrades at 50°C for 56 days.
  • Fig. 7 is a schematic structural view of an embolism provided according to an embodiment of the present invention.
  • the difference between Fig. 7 and Fig. 1 is that the connection between the embolus body and the developing element is different.
  • Fig. 8 is a schematic structural diagram of an embolism provided according to an embodiment of the present invention, in which the connection between the embolus body and the developing element is not shown.
  • FIG. 9 is a schematic structural view of an embolism provided by an embodiment of the present invention.
  • the pitch of the developing elements shown in FIG. 9 is larger than that of the developing elements shown in FIG. 8 .
  • each embodiment of the content described below has one or more technical features, but this does not mean that the inventor must implement all the technical features in any embodiment at the same time, or can only implement different embodiments separately. Some or all of the technical features. In other words, on the premise that the implementation is possible, those skilled in the art can selectively implement some or all of the technical features in any embodiment according to the disclosure of the present invention and depending on design specifications or implementation requirements, or Selectively implement a combination of some or all of the technical features in multiple embodiments, thereby increasing the flexibility of the implementation of the present invention.
  • the singular forms “a”, “an” and “the” include plural objects, and the plural form “a plurality” includes two or more objects, unless the content clearly states otherwise.
  • the term “or” is generally used in the sense including “and/or”, unless the content clearly indicates otherwise, and the terms “install”, “connect” and “connect” should be To understand it in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection. It can be a mechanical connection or an electrical connection. It can be directly connected or indirectly connected through an intermediary, and it can be the internal communication of two elements or the interaction relationship between two elements. Those of ordinary skill in the art can understand the specific meanings of the above terms in the present invention according to specific situations.
  • proximal refers to the relative orientation, relative position, direction of elements or actions relative to each other from the perspective of a doctor using the medical device, although “proximal”, “distal ” is not limiting, but “proximal” generally refers to the end of the medical device that is closest to the practitioner during normal operation, and “distal” generally refers to the end that enters the patient first.
  • FIG. 1 shows a schematic structural view of an embolism 100 provided by an embodiment of the present invention, and the embolism 100 shown in FIG. 1 is in its linear primary shape.
  • the emboli 100 is a relatively long tubular member extending from its proximal end to its distal end.
  • the proximal end of the embolism 100 is configured to be connected with a pushing device (not shown in the figure) of the embolism 100, so that the embolism 100 can be pushed to a target position by the pushing device.
  • the embolism 100 may be applied to interventional treatment of vascular diseases, and the target location may be an aneurysm cavity of a hemangioma, such as an aneurysm.
  • the plug 100 includes a plug body 110, and the plug body 110 is a helical part formed by helically winding a wire.
  • the wire is made of polylactic acid-glycolic acid copolymer, and in terms of weight percentage, the proportion of lactic acid in the polylactic acid-glycolic acid copolymer is 80% to 85%, which makes the degradation time of the wire at a predetermined temperature more than 6 months.
  • the predetermined temperature refers to the body cavity temperature of the patient, and its value may be 36.8°C-37.2°C.
  • the degradation time refers to the time required for the wire to degrade completely.
  • the degradation rate of the embolism body 110 is more appropriate, and can match the time of tumor cavity occlusion and tumor neck endothelialization, and will not complete the degradation before the tumor cavity is completely organized, effectively avoiding aneurysm recanalization, and can also alleviate or even relieve the aneurysm. mass effect.
  • Polylactic acid-glycolic acid copolymer can be biodegraded, and the types of degradation include hydrolysis, thermal decomposition, photolysis, enzymatic decomposition, etc.
  • the hydrolysis reaction of the ester bond mainly occurs, and the hydrolysis reaction can be preferentially in the amorphous region (when the polylactic acid-glycolic acid is half crystalline polymers).
  • lactic acid degradation products including lactic acid dimer, glycolic acid-lactic acid dimer or other small molecular monomers are released.
  • the reaction equation is:
  • These weakly acidic degradation products can be metabolized by the body. At the same time, these weakly acidic degradation products can also change the local tissue ecological microenvironment (for example, change the pH value in the tumor cavity), thereby inducing inflammation, stimulating the activation of platelet factors, and further activating the body's immune system. The immune mechanism of the cells promotes the thrombusization and organization of the tumor cavity.
  • the inventors have found that when the proportion of lactic acid is 80% to 85%, when the intrinsic viscosity of the polylactic acid-glycolic acid copolymer is 1.2dL/g to 2.0dL/g, and the weight average molecular weight is 200000g/mol to 500000 g
  • the polylactic acid-glycolic acid copolymer is a semi-crystalline polymer
  • the degradation rate of the polylactic acid-glycolic acid copolymer changes with temperature
  • the degradation rate of the polylactic acid-glycolic acid copolymer is about 37 °C
  • the time is longer, and the degradation rate matches the time of hemangioma occlusion and endothelialization of the tumor neck.
  • the polylactic acid-glycolic acid copolymer with a lactic acid ratio of 80% to 85%, an intrinsic viscosity of 1.2dL/g to 2.0dL/g, and a weight average molecular weight of 200000g/mol to 500000g/mol can be used to manufacture the polylactic acid-glycolic acid copolymer. wire, and then manufacture the plug body 110 .
  • the degradation characteristics of the plug body 110 will be described in detail later.
  • the crystallinity of the polylactic acid-glycolic acid copolymer used to manufacture the plug body 110 may not be less than 40%.
  • the breaking strength of the wire is greater than or equal to 200 MPa, the breaking elongation is greater than or equal to 10%, and the thermal shrinkage is less than or equal to 25%.
  • the wire After removing the thermal history, the wire has a glass transition temperature of 50°C to 60°C.
  • the wire is spirally wound along a mandrel with a diameter of about 0.003"-0.010" to form the plug body 110 at a winding speed of 5r/s-50r/s, and then the plug body 110 is heat-treated to stabilize its helical configuration.
  • the plug body 110 has a relatively stable configuration at the predetermined temperature (ie about 37° C.), and no untwisting will occur.
  • the outer diameter of the plug body 110 may be 0.008"-0.020", and the inner diameter thereof is related to the cross-sectional area of the wire.
  • the cross section of the wire can be a circle, or a part of a circle, with a diameter of 0.001"-0.006".
  • the cross-section of the wire can also be in other shapes, such as rectangle, polygon, etc., which is not limited in this embodiment of the present invention.
  • the pitch of the plug body 110 may be 1-2 times the diameter of the cross-sectional area of the wire (when the cross-sectional area of the wire is a circle or a part of a circle).
  • Example 1 A plug body 110 prepared in the embodiment of the present invention was placed in PBS buffer at 37°C for a degradation experiment.
  • Figure 2 shows the relationship between the mass/weight average molecular weight loss and degradation time of the plug body 110 .
  • the mass loss of the plug body 110 is not obvious, and the plug body 110 basically maintains the integrity of the overall structure (as shown in FIG. 3 ).
  • the loss of the mass and weight average molecular weight of the plug body 110 basically reaches 50%, and the overall integrity of the plug body 110 is destroyed (as shown in FIG. 4 ).
  • the degradation lasts for more than 540 days, the loss of the mass and weight average molecular weight of the plug body 110 exceeds 80%, and the plug body 110 is degraded substantially completely.
  • the intrinsic viscosity of the plug body 110 is also tested, and the test results show that the loss of intrinsic viscosity also reaches 50%.
  • observing the appearance of the plug body 110 can confirm that its structural integrity has been damaged and macroscopic fractures have occurred.
  • Example 2 Put another plug body 110 prepared in the embodiment of the present invention in PBS buffer at 50°C for a degradation experiment, and take scanning electron micrographs of the plug body on the 14th and 56th days of degradation.
  • FIG. 5 when the degradation progresses to the 14th day, the degradation of the plug body 110 is not obvious, and the overall integrity is basically maintained.
  • Figure 6 when the degradation progressed to the 56th day, the structural integrity of the plug body 110 was destroyed, and the intrinsic viscosity and weight-average molecular weight of the plug body 110 both lost more than 50%, and basically met the first-class Degradation law.
  • the degradation lasts for more than 8 months, the appearance of the plug body 110 is observed and it is found that the plug body is basically completely degraded.
  • Comparative Example 1 A helical part prepared from poly(lactic acid-glycolic acid) with a lactic acid content of about 10% was placed in PBS buffer and degraded at 37°C.
  • the only difference between the helical part and the plug body 110 provided in the first and second embodiments is that the lactic acid content in the raw material is different, and the glass transition temperature of the helical part after eliminating the thermal history is different due to the different lactic acid content. It is 40°C to 50°C.
  • the helical part is mechanically degraded within 3 to 6 months. The occlusion of the tumor cavity and the endothelialization of the tumor neck usually take more than 6 months.
  • the helical part if the helical part is implanted into the tumor cavity, it will be degraded before the tumor cavity is completely thrombusized and organized, resulting in tumor cavity
  • the density of the internal embolism decreased, and there was a possibility of hemangioma recanalization.
  • the stability of the spiral part is relatively poor, and higher packaging requirements are required to avoid unexpected premature degradation during the shelf life (storage time after packaging).
  • Comparative Example 2 A helical part prepared from polylactic acid-glycolic acid with a lactic acid content of about 50% was placed in PBS buffer and degraded at 37°C.
  • the only difference between the screw part and the plug body 110 provided in the first and second embodiments is the content of lactic acid in the raw materials.
  • the polylactic acid-glycolic acid in this comparative example is a non-crystalline polymer.
  • the helical part in this comparative example degrades completely within 2-4 months.
  • the embolization body 110 provided by the embodiment of the present invention can promote the thrombusization and organization of the tumor cavity fully, and can be completely degraded after the organization is complete, so as to avoid aneurysm recanalization, and relieve even Remove mass effect.
  • the plug body 110 has a first lumen 111 extending through the axial direction thereof.
  • the embolism 100 further includes a developing element 120, the developing element 120 is arranged in the first inner cavity 111 and connected with the embolism body 110 for During the process of implanting the embolism 100 into the tumor cavity, the pose of the embolism 100 is displayed by an imaging device.
  • pose includes position and attitude.
  • the developing element 120 can be a tubular member having a second lumen 121, and its length preferably matches the length of the plug body 110 (that is, the developing element 120 is equal in length to the plug body 110, or the developing The element 120 is slightly shorter than the plug body 110) to allow visualization of the plug 100 throughout its axial length.
  • the developing element 120 may specifically be a spiral component or a tube mesh component.
  • the material of the developing element 120 may be a radiopaque metal, including but not limited to platinum, iridium, gold, silver, tantalum and tungsten or an alloy thereof.
  • a metal wire made of the above materials is spirally wound on a mandrel with a predetermined diameter to form the developing element 120 in a helical structure.
  • the developing element 120 is braided by metal wires made of the above materials to form a pipe network structure.
  • the metal tube made of the above materials is laser engraved to form the developing element 120 in the shape of a tube network.
  • the material of the developing element 120 can also be a composite material, and the composite material includes a matrix, and the matrix is doped with a developing substance.
  • the matrix includes but is not limited to any one of polylactic acid, polycaprolactone polyglycolic acid, lactic acid-glycolic acid copolymer, polydioxanone, polyurethane, chitosan and hyaluronic acid or several.
  • the imaging substance includes iodine contrast agent (such as iohexol, iodized oil, etc.) or barium sulfate.
  • the filament made of the composite material may be braided to form the developing member 120 , or the filament made of the composite material may be helically wound on a mandrel of a predetermined diameter to form the developing member 120 .
  • the ratio of the volume of the developing element 120 to the volume of the plug body 110 is less than or equal to 50%.
  • the volume of the developing element 120 refers to the volume of the space occupied by the developing element 120.
  • the volume of the space occupied by the tubular component has a value of The product of the cross-sectional area of the developing element 120 and the length of the developing element 120 .
  • the volume of the plug body 110 refers to the volume of space occupied by the tubular part of the plug body 110, and its value is the product of the cross-sectional area of the plug body 110 and the length of the plug body 110 .
  • the developing element 120 made of certain materials is non-degradable, the smaller the volume of the developing element 120, the better, so as to alleviate the occupying effect to the greatest extent.
  • the outer diameter of the developing element 120 may be 0.003"-0.010", and the inner diameter may be 0.001"-0.008".
  • the pitch of the developing element 120 can be 1 to 2 times the diameter of the wire forming the helical structure (when the cross section of the wire is circular or round part of the shape).
  • the developing element 120 may not be a tubular structure, but a single strand or multi-strand wire, as long as it can display the posture (ie position and posture) of the embolic object 100 .
  • the developing element 120 can be connected with the plug body 110 in any suitable way.
  • an atraumatic junction 130 is formed at the end of the embolism 100 , such as the distal end, by means of thermal melting or dispensing, and the development element is attached by using the junction 130 .
  • the distal end of 120 and the distal end of the plug body 110 are firmly connected together, that is, the partial structure of the distal end of the plug body 110 and the partial structure of the distal end of the developing element 120 are covered by the joint portion 130 middle.
  • the joint portion 130 is preferably a ball cap structure.
  • the proximal end of the developing element 120 can be connected with the proximal end of the plug body 110 in the same way.
  • the developing element 120 and the plug body 110 are wound and connected by binding wires 140 , and the position of the binding can be determined according to actual conditions.
  • the embolism 100 also includes a shaping element (not shown in the figure), which is used to keep the embolism 100 in a preset shape, improve the support and stability of the embolism 100 stability.
  • the embolism 100 has a preset secondary configuration
  • the secondary configuration is a 2D or 3D three-dimensional shape, such as a wave shape, a spiral shape, a polyhedron shape (such as a tetrahedron shape, a pentahedron shape or Hexahedral), etc.
  • the material of the shaping element may comprise a shape memory alloy, for example, the shaping element is entirely made of a shape alloy, wherein the shape alloy includes but is not limited to nickel titanium alloy, nitinol, cobalt chromium alloy, nickel cobalt alloy, or A part of the material used to make the shaped element is a shape memory alloy, such as DFT (drawn filled tube), those skilled in the art know that DFT includes an inner core and an outer tube, and the material of the inner core is platinum, iridium, One of gold, silver, tantalum and tungsten or its alloy, and the outer material is one or more of shape memory alloys such as nickel-titanium alloy, nitinol, cobalt-chromium alloy, and nickel-cobalt alloy.
  • DFT drawn filled tube
  • the shaping element is pre-shaped according to the secondary configuration of the plug 100, that is, when the secondary configuration of the plug 100 is wave-shaped, the shaping element is pre-shaped into a wave shape, when the When the secondary configuration of the plug 100 is a helical shape, the shape-setting element is pre-shaped into a helical shape, and when the secondary configuration of the plug 100 is a polyhedral shape, the shape-setting element is pre-shaped into a polyhedral shape.
  • the shaping element is arranged in the first inner cavity 111 of the plug body 110, and at least one end of the shaping element can pass through the
  • the joint part 130 is connected with the plug body 110 , or the shaping element can also be connected with the plug body 110 through the binding wire 140 .
  • the shaping element is disposed in the second inner cavity 121, and at least one end of the shaping element is connected to the plug body through the joint portion 130 110 connections.
  • the shaping element can be a tubular component, such as a spiral component or a tube mesh component, or a single or multiple strands of wire.
  • the ratio of the volume of the shaping element to the volume of the plug body 110 is less than or equal to 10%. It can be understood that the shaping element is not degradable, so it should have as small a volume as possible on the premise of supporting the plug body 110 so that the plug 100 maintains a preset shape, so as to further alleviate the occupying effect .
  • the preparation method of the plug 100 includes: step S1: shaping the wound plug body 110 into a secondary configuration according to a preset shape; and The developing element 120 is shaped into a secondary configuration according to a preset shape.
  • Step S2 using any suitable method to place the developing element 120 in the first inner cavity 111 of the plug body 110 .
  • Step S3 Connect the distal end of the developing element 120 to the distal end (or proximal end) of the plug body 110 .
  • Step S4 Adjusting the poses of the developing element 120 and the plug body 110 so that the developing element 120 and the plug body 110 are arranged coaxially or axially parallel.
  • Step S5 Connect the proximal end of the developing element 120 to the proximal (or distal) end of the plug body 110 . This step is adopted according to actual needs.
  • the preparation method of the embolism 100 includes: step S10: placing the shaping element Follow preset shapes.
  • the plug body 110 and the developing element 120 may also be shaped according to a preset shape.
  • Step S20 setting the developing element 120 in the first inner cavity 111 of the plug body 110 in any suitable way, and setting the shaping element in the second inner cavity 121 of the developing element 120 middle.
  • the shaping element is a single-strand wire, which can be achieved by stretching the plug body 110 and the developing element 120 into a linear primary shape (that is, stretching the plug body 110 and the developing element 120 into a columnar configuration) ), and then use a pushing device to push the developing element 120 into the first inner cavity 111 , then stretch the shaping element into a linear shape, and pass it through the second inner cavity 121 .
  • Step S30 Connect the distal end of the developing element 120 to the distal end of the plug body 110 , and connect the distal end of the shaping element to the distal (or proximal) end of the plug body 110 .
  • Step S40 Adjust the relative poses of the plug body 110, the developing element 120, and the shaping element so that the plug body 110, the developing element 120, and the shaping element are coaxial or axially parallel layout.
  • Step S50 Connect the proximal end of the developing element 120 to the proximal end of the plug body 110 , and connect the proximal end of the shaping element to the proximal (or distal) end of the plug body 110 . This step is adopted according to actual needs.
  • the step S20 is specifically to use any suitable method to arrange the developing element 120 and the shaping component in the first cavity. In the lumen 111.
  • the degradation time of the embolic body of the embolus can be matched with the time of tumor cavity occlusion and tumor neck endothelialization, and it can be completely degraded after the tumor cavity is fully organized, avoiding
  • the complete degradation during the process of mechanization leads to a decrease in the packing density in the tumor cavity and causes the problem of hemangioma recanalization.
  • after the embolism body is completely degraded it can effectively alleviate or even completely eliminate the compression of the tumor body on the peripheral nerve or tissue, and slow down the mass effect.
  • the plug body is nested on the outside of the developing element, and is completely made of degradable polymer material, with a relatively smooth outer surface, so the plug has sufficient softness during pushing, and pushes There is less resistance.

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Abstract

本发明提供了一种栓塞物，包括栓塞本体，所述栓塞本体为螺旋部件，且所述栓塞本体的材料是聚乳酸-羟基乙酸共聚物，且以重量百分比计，乳酸的比例为80％～85％，以使得所述栓塞本体在预定温度下的降解时间大于6个月。所述预定温度为患者的体腔温度，该栓塞物在植入血管瘤的瘤腔后，栓塞本体的降解时间与瘤腔机化及瘤颈内皮化的时间相适应，能够有效避免血管瘤再通，并在栓塞本体降解完全后缓解甚至解除占位效应。

Description

一种栓塞物 技术领域
本发明涉及医疗器械技术领域，具体涉及一种栓塞物。
背景技术
颅内动脉瘤是一种常见的脑血管疾病，其是由多种因素造成的颅内动脉壁结构破坏、管壁异常膨出，是引发蛛网膜下腔出血的重要原因之一。近年来，随着影像学和材料学的进步，推动了介入治疗颅内动脉瘤的迅猛发展，其中弹簧圈栓塞是一种常见治疗手段。弹簧圈栓塞动脉瘤，一方面可以减轻血流对动脉瘤瘤壁的冲击，另一方面能够诱导瘤腔内血栓形成和血栓机化，实现动脉瘤的闭塞。
临床研究发现，有较高比例的大型和巨大型动脉瘤是以占位效应起病。目前常见的用于介入治疗的弹簧圈多为惰性金属材质，对于占位效应的缓解或解除尚有欠缺。市面上已有的类似“生物修饰弹簧圈”概念的产品，这些产品利用可降解高分子材料对金属弹簧圈进行修饰，但所用的高分子材料的降解速率较快，通常在3-6个月内完全降解。然而，临床数据表明，在使用支架的情况下，内皮化的时间约为6个月，因此利用这些生物修饰弹簧圈产品进行动脉瘤的介入治疗时，若高分子材料在产品中的体积比例较高，则在高分子材料降解完全时，瘤腔内尚未完全机化形成纤维组织，因高分子材料的降解导致的栓塞密度下降存在动脉瘤再通的风险，但是若高分子材料在产品中的体积比例较小，瘤腔完全机化后又不能有效缓解占位效应。
发明内容
本发明的目的在于提供一种栓塞物，其用于植入血管瘤的瘤腔以促进瘤腔内血栓机化，避免动脉瘤再通，且在瘤腔完全闭塞后有效缓解占位效应。
为实现上述目的，本发明提供了一种栓塞物，包括栓塞本体，所述栓塞本体为螺旋部件，且所述栓塞本体的材料是聚乳酸-羟基乙酸共聚物，且以重量百分比计，乳酸的比例为80％～85％，以使得所述栓塞本体在预定温度下的降解时间大于6个月。
可选地，所述聚乳酸-羟基乙酸共聚物的特性粘度为1.2dL/g～2.0dL/g，重均分子量为200000g/mol～500000g/mol。
可选地，所述栓塞本体由线材螺旋绕制形成，所述线材的断裂强度大于或等于200MPa，断裂伸长率大于或等于10％，热收缩率小于或等于25％。
可选地，所述聚乳酸-羟基乙酸共聚物的结晶度大于或等于40％。
可选地，聚乳酸-羟基乙酸共聚物的玻璃化转变温度为50℃～60℃。
可选地，所述栓塞本体为具有第一内腔的管状部件；所述栓塞物还包括显影元件，所述显影元件设置于所述第一内腔中，并与所述栓塞本体连接。
可选地，所述显影元件为不透射线金属制成的金属部件；或者，所述显影元件为基体中掺杂有显影物质的复合材料部件，其中，所述显影物质为碘造影剂或硫酸钡，所述基体为聚乳酸、聚己内酯聚羟基乙酸、乳酸-羟基乙酸共聚物、聚对二氧杂环己酮、聚氨酯、壳聚糖和透明质酸中的任意一种或几种。
可选地，所述显影元件为具有第二内腔的管状部件，且所述显影元件的长度与所述栓塞本体的长度相匹配。
可选地，所述显影元件为螺旋部件，或者所述显影元件为管网状部件。
可选地，所述显影元件的体积与所述栓塞本体的体积之比小于或等于50％。
可选地，所述栓塞物还包括定型元件，所述定型元件设置于所述第二内腔中，并与所述栓塞本体连接，且用于使所述栓塞物保持为预设的形状。
可选地，所述栓塞本体为具有第一内腔的管状部件；所述栓塞物还包括 定型元件，所述定型元件设置于所述第一内腔中并与所述栓塞本体连接，且用于使所述栓塞物保持为预设的形状。
可选地，所述定型元件的体积与所述栓塞本体的体积的比值小于或等于10％。
与现有技术相比，本发明的栓塞物具有如下优点：
前述的栓塞物包括栓塞本体，所述栓塞本体为螺旋部件，且所述栓塞本体的材料是聚乳酸-羟基乙酸共聚物，且以重量百分比计，乳酸的比例为80％～85％，以使得所述栓塞本体在预定温度下的降解时间大于6个月。所述预定温度是指与人体内环境温度，具体值为37℃左右，例如36.8℃～37.2℃。所述栓塞物用于植入血管瘤的瘤腔中，并促进血管瘤血栓化和机化，且该栓塞本体的降解速率较为适宜，能够配合瘤腔闭塞及瘤颈内皮化的时间，不会在瘤腔完全机化之前完成降解，有效避免血管瘤再通，且还能够缓解甚至解除占位效应。
所述聚乳酸-羟基乙酸共聚物的特性粘度为1.2dL/g～2.0dL/g，重均分子量为200000g/mol～500000g/mol。尤其地，所述栓塞本体由线材螺旋绕制而成，且所述线材的断裂强度大于或等于200MPa，断裂伸长率大于或等于10％，热收缩率小于或等于25％，该栓塞本体能够在所述预定温度下保持结构的稳定性，避免发生解旋，也就是说，所述栓塞物在体内可以保持为螺旋部件，并有效填塞瘤腔，促进瘤腔血栓化及机化。
附图说明
附图用于更好地理解本发明，不构成对本发明的不当限定。
图1是本发明根据一实施例所提供的栓塞物的结构示意图。
图2是本发明实施例所提供的栓塞物的栓塞本体在37℃条件下降解时的质量/重均分子量损失与时间的关系图。
图3是本发明实施例所提供的栓塞物的栓塞本体在37℃条件下降解120天时的扫描电镜图。
图4是本发明实施例所提供的栓塞物的栓塞本体在37℃条件下降解270天时的扫描电镜图。
图5是本发明实施例所提供的栓塞物的栓塞本体在50℃条件下降解14天时的扫描电镜图。
图6是本发明实施例所提供的栓塞物的栓塞本体在50℃条件下降解56天时的扫描电镜图。
图7是本发明根据一实施例所提供的栓塞物的结构示意图，图7与图1的区别在于栓塞本体与显影元件的连接方式不同。
图8是本发明根据一实施例所提供的栓塞物的结构示意图，图中未示出栓塞本体与显影元件的连接方式。
图9是本发明根据一实施例所提供的栓塞物的结构示意图，图9中所示的显影元件的节距大于图8所示的显影元件的节距。
附图标记说明如下：100-栓塞物，110-栓塞本体，111-第一内腔，120-显影元件，121-第二内腔。
具体实施方式
以下通过特定的具体实例说明本发明的实施方式，本领域技术人员可由本说明书所揭露的内容轻易地了解本发明的其他优点与功效。本发明还可以通过另外不同的具体实施方式加以实施或应用，本说明书中的各项细节也可以基于不同观点与应用，在没有背离本发明的精神下进行各种修饰或改变。需要说明的是，本实施例中所提供的图示仅以示意方式说明本发明的基本构想，遂图式中仅显示与本发明中有关的组件而非按照实际实施时的组件数目、形状及尺寸绘制，其实际实施时各组件的型态、数量及比例可为一种随意的 改变，且其组件布局型态也可能更为复杂。
另外，以下说明内容的各个实施例分别具有一或多个技术特征，然此并不意味着使用本发明者必需同时实施任一实施例中的所有技术特征，或仅能分开实施不同实施例中的一部或全部技术特征。换句话说，在实施为可能的前提下，本领域技术人员可依据本发明的公开内容，并视设计规范或实作需求，选择性地实施任一实施例中部分或全部的技术特征，或者选择性地实施多个实施例中部分或全部的技术特征的组合，借此增加本发明实施时的弹性。
如在本说明书中所使用的，单数形式“一”、“一个”以及“该”包括复数对象，复数形式“多个”包括两个以上的对象，除非内容另外明确指出外。如在本说明书中所使用的，术语“或”通常是以包括“和/或”的含义而进行使用的，除非内容另外明确指出外，以及术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接。可以是机械连接，也可以是电连接。可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通或两个元件的相互作用关系。对于本领域的普通技术人员而言，可以根据具体情况理解上述术语在本发明中的具体含义。
在本文中，术语“近端”、“远端”是从使用该医疗器械的医生角度来看相对于彼此的元件或动作的相对方位、相对位置、方向，尽管“近端”、“远端”并非是限制性的，但是“近端”通常指该医疗设备在正常操作过程中靠近医生的一端，而“远端”通常是指首先进入患者体内的一端。
为使本发明的目的、优点和特征更加清楚，以下结合附图对本发明作进一步详细说明。需说明的是，附图均采用非常简化的形式且均使用非精准的比例，仅用以方便、明晰地辅助说明本发明实施例的目的。附图中相同或相似的附图标记代表相同或相似的部件。
图1示出了本发明一实施例所提供的栓塞物100的结构示意图，且图1所示的栓塞物100处于其线性初级形状。如图1所示，所述栓塞物100为从 其近端延伸至其远端的长度较大的管状部件。所述栓塞物100的近端被设置用于与该栓塞物100的推送装置(图中未示出)连接，以使所述栓塞物100能够被所述推送装置推送至目标位置。所述栓塞物100可以应用于血管疾病的介入治疗，所述目标位置可以是血管瘤的瘤腔，所述血管瘤例如是动脉瘤。
所述栓塞物100包括栓塞本体110，所述栓塞本体110是由线材螺旋绕制而成的螺旋部件。所述线材由聚乳酸-羟基乙酸共聚物制成，且以重量百分比计，聚乳酸-羟基乙酸共聚物的乳酸的比例为80％～85％，这使得所述线材在预定温度下的降解时间大于6个月。这里，所述预定温度是指患者的体腔温度，其值可以为36.8℃～37.2℃。所述降解时间是指所述线材完全降解所需要的时间。因此所述栓塞本体110的降解速率较为适宜，能够配合瘤腔闭塞及瘤颈内皮化的时间，不会在瘤腔完全机化之前完成降解，有效避免动脉瘤再通，且还能够缓解甚至解除占位效应。
聚乳酸-羟基乙酸共聚物可发生生物降解，降解的类型包括水解、热分解、光分解、酶分解等。当由聚乳酸-羟基乙酸共聚物制备而成的植入物植入瘤腔时，其主要发生酯键的水解反应，且该水解反应可优先在非晶区(当聚乳酸-羟基乙酸为半结晶型聚合物时)进行。酯键水解时释放出包括乳酸二聚体、乙醇酸-乳酸二聚体或其他小分子单体在内的乳酸性降解产物，反应方程为：
Figure PCTCN2022138570-appb-000001
这些弱酸性降解产物可被机体代谢，同时这些弱酸性降解产物还可以改变局部组织生态微环境(例如改变瘤腔内的pH值)，进而诱发炎症，刺激活血小板因子，并进一步激活机体的免疫细胞的免疫机制，促使瘤腔血栓化及机化。
发明人研究发现，在乳酸比例为80％～85％的情况下，当聚乳酸-羟基乙酸共聚物的特性粘度为1.2dL/g～2.0dL/g、重均分子量为200000g/mol～500000 g/mol时，聚乳酸-羟基乙酸共聚物为半结晶型聚合物，该聚乳酸-羟基乙酸共聚物的降解速度随温度发生变化，且该聚乳酸-羟基乙酸在37℃左右的条件下的降解时间较长，降解速度与血管瘤闭塞及瘤颈内皮化的时间相匹配。因此，可以利用乳酸比例为80％～85％、特性粘度为1.2dL/g～2.0dL/g、且重均分子量为200000g/mol～500000g/mol的聚乳酸-羟基乙酸共聚物来制造所述线材，进而制造所述栓塞本体110。所述栓塞本体110的降解特性具体将在后文中进行说明。实践中，用于制造所述栓塞本体110的聚乳酸-羟基乙酸共聚物的结晶度可不小于40％。
可选地，所述线材的断裂强度大于或等于200MPa，断裂伸长率大于或等于10％，热收缩率小于或等于25％。在消除热历史之后，所述线材的玻璃化转变温度为50℃～60℃。所述线材沿一直径约为0.003”～0.010”的芯轴螺旋绕制以形成所述栓塞本体110，绕制转速为5r/s～50r/s，之后对所述栓塞本体110进行热处理以稳定其螺旋构型。所述栓塞本体110在所述预定温度(即37℃左右)下具有较为稳定的构型，不会发生解旋。另外，所述栓塞本体110的外径可以为0.008”～0.020”，其内径与所述线材的横截面积有关。可选地，所述线材的横截面可以为圆形，或圆形的一部分，其直径为0.001”～0.006”。所述线材的横截面也可以是其他形状，例如长方形、多边形等，本发明实施例对此不作限定。所述栓塞本体110的节距可以为所述线材的横截面积的直径(当所述线材的横截面积为圆形或圆形的一部分时)的1～2倍。
接下去通过对比实验说明本发明实施例所提供的栓塞本体110的降解特性。
实施例一：将本发明实施例制备的一栓塞本体110置于37℃的PBS缓冲液中进行降解实验，图2示出了所述栓塞本体110的质量/重均分子量损失与降解时间关系图。参考图2，在降解初期(1-200天)，所述栓塞本体110的质量损失不明显，且所述栓塞本体110基本保持整体结构的完整性(如图3所 示)。当降解进行到200～300天时，所述栓塞本体110的质量和重均分子量的损失基本达到50％，且所述栓塞本体110的整体完整性发生破坏(如图4所示)。从降解开始到降解进行至340天左右时，所述栓塞本体110的重均分子量的对数Y与时间X的相关方程为：Y＝-0.0175X+13.772，相关系数R 2为0.9723，降解过程基本符合一级降解规律。当降解进行到540天以上时，所述栓塞本体110的质量和重均分子量的损失均超过80％，所述栓塞本体110基本降解完全。在降解进行到200～300天时，还对所述栓塞本体110进行特性粘度的测试，测试结果显示其特性粘度损失也达到50％。同时，观察所述栓塞本体110的外观可确定其结构完整性发生破坏，并出现宏观断裂。
实施例二：将本发明实施例制备的另一栓塞本体110置于50℃的PBS缓冲液中进行降解实验，并在降解的第14天和第56天对所述栓塞本体拍摄扫描电镜照片。如图5所示，当降解进行到第14天时，所述栓塞本体110的降解不明显，并基本保持整体完整性。如图6所示，当降解进行到第56天时，所述栓塞本体110的结构完整性发生破坏，所述栓塞本体110的特性粘度和重均分子量的损失均超过50％，且基本符合一级降解规律。在降解进行到8个月以上时，观察所述栓塞本体110的外观发现所述栓塞本体基本降解完全。
对比例一：将一由乳酸含量约为10％的聚乳酸-羟基乙酸所制备的螺旋部件置于PBS缓冲液中，且在37℃的条件下进行降解。该螺旋部件与实施例一及实施例二所提供的栓塞本体110的区别之处仅在于原材料中的乳酸含量不同，以及，因乳酸含量不同使得该螺旋部件在消除热历史后的玻璃化转变温度为40℃～50℃。该螺旋部件在3～6个月的时间内机化完全降解。瘤腔的闭塞及瘤颈的内皮化时间通常在6个月以上，因此若将该螺旋部件植入瘤腔，其将在瘤腔完全血栓话及机化前就已经降解完成，并导致瘤腔内栓塞密度下降，进而存在血管瘤再通的可能性。另外，该螺旋部件的稳定性相对较差，需要具有更高的包装要求，以避免其在货架期(包装后的存储时间)就发生 非预期的提前降解。
对比例二：将一由乳酸含量约为50％的聚乳酸-羟基乙酸所制备的螺旋部件置于PBS缓冲液中，且在37℃的条件下进行降解。该螺旋部件与实施例一及实施例二所提供的栓塞本体110的区别之处仅在于原材料中的乳酸含量不同。另外，由于乳酸含量不同使得该对比例中的聚乳酸-羟基乙酸为非结晶型聚合物。该对比例中的螺旋部件在2-4个月内降解完成。
因此，本发明实施例所提供的栓塞本体110在植入瘤腔后，促使瘤腔充分地血栓化及机化，并能够在机化完全后才彻底降解，避免动脉瘤再通，并缓解甚至解除占位效应。
所述栓塞本体110具有沿其轴向贯通地延伸的第一内腔111。如图2至图6所示，所述栓塞物100还进一步包括显影元件120，所述显影元件120设置于所述第一内腔111中，并与所述栓塞本体110连接，以用于在将所述栓塞物100植入瘤腔的过程中，通过影像装置显示所述栓塞物100的位姿。这里，位姿包括位置和姿态。
所述显影元件120可以是具有第二内腔121的管状部件，其长度优选与所述栓塞本体110的长度相匹配(即所述显影元件120与所述栓塞本体110等长，或者所述显影元件120略短于所述栓塞本体110)，以在轴向的全部长度范围内对所述栓塞物100进行显影。所述显影元件120具体可以是螺旋部件或管网状部件。
所述显影元件120的材料可以为不透射线金属，包括但不限于铂、铱、金、银、钽和钨中的一种或其合金。由上述材料制成的金属丝在一预设直径的芯轴上螺旋绕制形成螺旋结构的所述显影元件120。或者由上述材料制成的金属丝编织形成管网状结构的所述显影元件120。或者，由上述材料制作的金属管经激光雕刻形成管网状的所述显影元件120。
所述显影元件120的材料也可以是复合材料，所述复合材料包括基体，所 述基体中掺杂有显影物质。其中，所述基体包括但不限于聚乳酸、聚己内酯聚羟基乙酸、乳酸-羟基乙酸共聚物、聚对二氧杂环己酮、聚氨酯、壳聚糖和透明质酸中的任一种或几种。所述显影物质包括碘造影剂(例如碘海醇、碘化油等)或硫酸钡。由所述复合材料制成的丝材可以编织形成所述显影元件120，或由所述复合材料制成的丝材可以在一预设直径的芯轴上螺旋绕制形成所述显影元件120。
可选地，所述显影元件120的体积与所述栓塞本体110的体积的比值小于或等于50％。所述显影元件120的体积是指，所述显影元件120所占据的空间体积，举例来说，当所述显影元件120为管状部件时，该管状部件所占据的空间体积，其值为所述显影元件120的横截面的面积与所述显影元件120的长度的乘积。同理，所述栓塞本体110的体积是指作为所述栓塞本体110的管状部件所占据的空间体积，其值为所述栓塞本体110的横截面的面积与所述栓塞本体110的长度的乘积。由于某些材料制成的所述显影元件120不可降解，那么此类显影元件120的体积越小越好，以最大限度地缓解占位效应。另外，所述显影元件120的外径可以为0.003”～0.010”，内径可以为0.001”～0.008”。当所述显影元件120为螺旋结构时，所述显影元件120的节距可以为形成所述螺旋结构的丝材的直径的1～2倍(当所述丝材的横截面为圆形或圆形的一部分时)。
替代性地，所述显影元件120也可以不是管状结构，而是单股或多股丝材，只要其能够显示所述栓塞物100的位姿(即位置和姿态)即可。
所述显影元件120可采用任意合适的方式与所述栓塞本体110连接。举例来说，如图1所示，在所述栓塞物100的端部例如远端通过热熔或点胶的方式形成无创伤性的接合部130，利用所述接合部130将所述显影元件120的远端与所述栓塞本体110的远端牢固地连接在一起，即所述栓塞本体110的远端的部分结构与所述显影元件120的远端的部分结构包覆于该接合部130中。 所述接合部130优选为球帽结构。类似地，可采用同样的方式使所述显影元件120的近端与所述栓塞本体110的近端连接。或者，如图7所示，所述显影元件120与所述栓塞本体110通过绑扎线140缠绕并绑扎连接，绑扎的位置可根据实际情况确定。
再进一步地，所述栓塞物100还包括定型元件(图中未示出)，所述定型元件用于使所述栓塞物100保持为预设的形状，提高所述栓塞物100的支撑性和稳定性。
详细来说，所述栓塞物100具有预设的二级构型，所述二级构型为2D或3D的立体形态，例如波浪形、螺旋形、多面体形(例如四面体形、五面体形或六面体形)等。所述定型元件的材料可以包括形状记忆合金，例如所述定型元件完全由形状合金制造而成，其中，形状合金包括但不限于镍钛合金、镍钛诺、钴铬合金、镍钴合金，或者用于制造所述定型元件的材料的一部分为形状记忆合金，例如DFT(drawn filled tube)，本领域技术人员知晓，DFT包括内芯和外层管，所述内芯的材料为铂、铱、金、银、钽和钨中的一种或其合金，而外层材料则为镍钛合金、镍钛诺、钴铬合金、镍钴合金等形状记忆合金中的一种或多种。所述定型元件根据所述栓塞物100的二级构型被预先定型，即当所述栓塞物100的二级构型为波浪形时，所述定型元件被预塑为波浪形，当所述栓塞物100的二级构型为螺旋形，所述定型元件被预塑为螺旋形，当所述栓塞物100的二级构型为多面体形时，所述定型元件被预塑为多面体形。
当所述显影元件120不具有所述第二内腔121时，所述定型元件设置于所述栓塞本体110的所述第一内腔111中，且所述定型元件的至少一端可通过所述接合部130与所述栓塞本体110连接，或者所述定型元件也可通过所述绑扎线140与所述栓塞本体110连接。当所述显影元件120具有所述第二内腔121时，所述定型元件设置于所述第二内腔121中，且所述定型元件的至少一 端通过所述接合部130与所述栓塞本体110连接。
进一步地，所述定型元件可以是管状部件，例如螺旋部件或管网状部件，也可以是单股或多股线材。另外，所述定型元件的体积与所述栓塞本体110的体积的比值小于或等于10％。可以理解的是，所述定型元件不可降解，因此其在支撑所述栓塞本体110以使所述栓塞物100保持预设形状的前提下，应当具有尽可能小的体积，以进一步缓解占位效应。
接下去对所述栓塞物100的制备方法进行介绍。
当所述栓塞物100不包括所述定型元件时，所述栓塞物100的制备方法包括：步骤S1：将绕制好的所述栓塞本体110按照预设的形状定型为二级构型；以及将所述显影元件120按照预设好的形状定型为二级构型。步骤S2：采用任意合适的方法使所述显影元件120设置于所述栓塞本体110的所述第一内腔111中。步骤S3：使所述显影元件120的远端与所述栓塞本体110的远端(或近端)连接。步骤S4：调整所述显影元件120和所述栓塞本体110的位姿，以使所述显影元件120与所述栓塞本体110同轴或轴向平行地布置。步骤S5：使所述显影元件120的近端与所述栓塞本体110的近端(或远端)连接。本步骤根据实际需要采用。
当所述栓塞物100包括所述定型元件，且所述显影元件120为具有所述第二内腔121的管状部件时，所述栓塞物100的制备方法包括：步骤S10：将所述定型元件按照预设的形状进行定型。当然，本步骤中也可以按照预设的形状对所述栓塞本体110和所述显影元件120进行定型。步骤S20：采用任意合适的方式使所述显影元件120设置于所述栓塞本体110的第一内腔111中，以及使所述定型元件设置于所述显影元件120的所述第二内腔121中。例如所述定型元件为单股丝材，可通过将所述栓塞本体110、所述显影元件120拉伸为线性初级形状(即将所述栓塞本体110及所述显影元件120拉伸为柱状构型)，然后利用推送装置将所述显影元件120推入所述第一内腔111中，接着 将所述定型元件拉伸为直线型，并将其穿设于所述第二内腔121中。步骤S30：使所述显影元件120的远端与所述栓塞本体110的远端连接，以及使所述定型元件的远端与所述栓塞本体110的远端(或近端)连接。步骤S40：调整所述栓塞本体110、所述显影元件120及所述定型元件的相对位姿，以使所述栓塞本体110、所述显影元件120及所述定型元件同轴或轴向平行地布置。步骤S50：使所述显影元件120的近端与所述栓塞本体110的近端连接，以及使所述定型元件的近端与所述栓塞本体110的近端(或远端)连接。本步骤根据实际需要采用。
可以理解的，当所述显影元件120不具有所述第二内腔121时，所述步骤S20则具体为采用任意合适的方式使所述显影元件120和所述定型部件设置于所述第一内腔111中。
本发明实施例所提供的技术方案中，所述栓塞物的栓塞本体的降解时间能够与瘤腔闭塞及瘤颈内皮化的时间相配适，其在瘤腔完全机化之后才彻底降解，避免在机化进行过程中完全降解造成瘤腔内填塞密度下降引起血管瘤再通的问题。并且，在栓塞本体彻底降解后，可以有效缓解甚至完全消除瘤体对周围神经或组织的压迫，减缓占位效应。以及，所述栓塞本体嵌套在显影元件外侧，并完全由可降解的高分子材料制作而成，具有较为光滑的外表面，因此所述栓塞物在推送过程中具有足够的柔软度，且推送阻力较小。
虽然本发明披露如上，但并不局限于此。本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样，倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内，则本发明也意图包含这些改动和变型在内。

Claims (14)

  1. 一种栓塞物，其特征在于，包括栓塞本体，所述栓塞本体为螺旋部件，且所述栓塞本体的材料是聚乳酸-羟基乙酸共聚物，且以重量百分比计，乳酸的比例为80％～85％，以使得所述栓塞本体在预定温度下的降解时间大于6个月。
  2. 根据权利要求1所述的栓塞物，其特征在于，所述聚乳酸-羟基乙酸共聚物的特性粘度为1.2dL/g～2.0dL/g，重均分子量为200 000g/mol～500 000g/mol。
  3. 根据权利要求2所述的栓塞物，其特征在于，所述栓塞本体由线材螺旋绕制形成，所述线材的断裂强度大于或等于200MPa，断裂伸长率大于或等于10％，热收缩率小于或等于25％。
  4. 根据权利要求2所述的栓塞物，其特征在于，所述聚乳酸-羟基乙酸共聚物的结晶度大于或等于40％。
  5. 根据权利要求2-4中任一项所述的栓塞物，其特征在于，聚乳酸-羟基乙酸共聚物的玻璃化转变温度为50℃～60℃。
  6. 根据权利要求1-4中任一项所述的栓塞物，其特征在于，所述栓塞本体为具有第一内腔的管状部件。
  7. 根据权利要求6所述的栓塞物，其特征在于，所述栓塞物还包括显影元件，所述显影元件设置于所述第一内腔中，并与所述栓塞本体连接。
  8. 根据权利要求7所述的栓塞物，其特征在于，所述显影元件为不透射线金属制成的金属部件；或者，所述显影元件为基体中掺杂有显影物质的复合材料部件，其中，所述显影物质为碘造影剂或硫酸钡，所述基体为聚乳酸、聚己内酯聚羟基乙酸、乳酸-羟基乙酸共聚物、聚对二氧杂环己酮、聚氨酯、壳聚糖和透明质酸中的任意一种或几种。
  9. 根据权利要求7或8所述的栓塞物，其特征在于，所述显影元件为具有第二内腔的管状部件，且所述显影元件的长度与所述栓塞本体的长度相匹配。
  10. 根据权利要求9所述的栓塞物，其特征在于，所述显影元件为螺旋部件，或者所述显影元件为管网状部件。
  11. 根据权利要求9所述的栓塞物，其特征在于，所述显影元件的体积与所述栓塞本体的体积之比小于或等于50％。
  12. 根据权利要求9所述的栓塞物，其特征在于，所述栓塞物还包括定型元件，所述定型元件设置于所述第二内腔中，并与所述栓塞本体连接，且用于使所述栓塞物保持为预设的形状。
  13. 根据权利要求6-8中任一项所述的栓塞物，其特征在于，所述栓塞物还包括定型元件，所述定型元件设置于所述第一内腔中并与所述栓塞本体连接，且用于使所述栓塞物保持为预设的形状。
  14. 根据权利要求13所述的栓塞物，其特征在于，所述定型元件的体积与所述栓塞本体的体积的比值小于或等于10％。
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