Occluder and preparation method thereof

Abstract

The present disclosure provides an occluder and a preparation method thereof, wherein the occluder includes a bending area and a straight area, wherein the bending area includes a convex bending area and a concave bending area, the straight area is composed of a material of a monofilament, and the bending area is composed of a material with stimulus-responsive properties or a material with an expansion coefficient different from that of the monofilament. The preparation method includes selecting a biodegradable polymer material to prepare a block copolymer and extruding a monofilament, weaving the monofilament after adjusting the shape by a combination of temperature stimulation and mechanical force; or weaving in layers with materials of different expansion coefficients and then storing the same. The occluder disclosed in the present disclosure can restore the designed shape within the body temperature range, simplifying the locking structure and the locking steps during the implantation of the occluder. The preparation process does not require high-temperature shaping, which reduces energy consumption.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical devices, and in particular relates to an occluder and a preparation method thereof. Background Art

[0002] Traditional cardiac implantable occluders are mostly made of metal materials such as nickel-titanium alloys. Although these materials have good shape memory and superelasticity, they will remain permanently after being implanted in the human body, which may cause a series of long-term complications, such as postoperative conduction block, chronic inflammation (foreign body reaction), nickel allergy, etc. In addition, the existence of metal occluders also limits the possibility of patients receiving other treatments in the later stage, such as examinations in strong magnetic environments such as nuclear magnetic resonance or other interventional surgical treatments in the heart cavity.

[0003] In order to solve a series of problems of metal occluders, degradable occluders use polymer materials with good biocompatibility and degradability such as poly-L-lactic acid (PLLA), polydioxanone (PDO), and polycaprolactone (PCL). However, compared with traditional metal materials such as nickel-titanium alloy, the mechanical properties of these polymer materials are relatively weak, and their shape recovery ability may be affected to a certain extent. Summary of the invention

[0004] The problem to be solved by the present disclosure is that the existing degradable occluder cannot automatically restore the designed shape after passing through the delivery system.

[0005] In order to solve the above problems, the present disclosure provides an occluder.

[0006] In a first aspect, the present disclosure provides an occluder, comprising a bending region and a straight region connected to each other, wherein the bending region is made of a material having stimulus responsive properties and / or a material having a linear expansion coefficient different from that of the straight region.

[0007] In some embodiments, the bending region is made of a material having stimulus responsive properties.

[0008] In some embodiments, the material having stimulus-responsive properties recovers a designed shape under stimulation by temperature, light or electrical signals.

[0009] In some embodiments, the material having stimulus responsive properties is a block copolymer; the block copolymer may or may not include a monofilament material.

[0010] In some embodiments, the block copolymer comprises two or more degradable polymer materials selected from the group consisting of poly(L-lactic acid), poly(glycolic acid), polycaprolactone, polydioxanone, lactic acid-glycolic acid copolymer, or poly(lactic acid-glycolic acid) copolymer; the material of the monofilament comprises poly(L-lactic acid), poly(glycolic acid), polycaprolactone, polydioxanone, lactic acid-glycolic acid copolymer, or poly(lactic acid-glycolic acid) copolymer.

[0011] In some embodiments, the block copolymer comprises poly (L-lactic acid) and poly (caprolactone); the molar ratio of poly (L-lactic acid) to poly (caprolactone) in the block copolymer is 1:1 to 1:5.

[0012] In some embodiments, the bending region is made of a material having a linear expansion coefficient different from that of the monofilament; the linear expansion coefficient of the straight region is αL 0 The bending region includes a convex bending region and a concave bending region, and the linear expansion coefficient of the convex bending region is αL 1 The linear expansion coefficient of the concave bending area is αL 2 The linear expansion coefficient relationship between the convex bending area, the concave bending area and the straight area satisfies αL 1 >αL 0 >αL 2 ; The linear expansion coefficient of the convex bending area αL 1 is the linear expansion coefficient αL of the flat region 0 More than 10 times.

[0013] In some embodiments, the linear expansion coefficient of the convex bending area is αL 1 1.0×10 -3 / ℃~5.0×10 -3 / ℃; the linear expansion coefficient of the flat area αL 0 1.0×10 -5 / ℃~1.0×10 -4 / ℃; the linear expansion coefficient of the concave bending area αL 2 1.0×10 -5 / ℃~1.0×10 -4 / ℃.

[0014] In some embodiments, the material of the monofilament is polypropylene carbonate; the material of the bending region is a block copolymer with poly-L-lactic acid as one of the monomers.

[0015] In some embodiments, the occluder is woven layer by layer from one end to the other end, and the connection method of the layers formed by the straight area and the bent area is diamond mesh crochet; the diameter of the occluder is 12~36 mm; the convex bent area is arranged at a distance of 0~12 mm inward from the outermost side; the concave bent area is arranged at a position extending 0.5~3 mm from the angle between the disc and the waist to the disc and the waist respectively; each straight area is 0.5~3 mm.

[0016] In some embodiments, the occluder skeleton includes a first disc portion, a waist portion, and a second disc portion connected in sequence from far to near, and a convex bending area and a concave bending area are formed in the first disc portion, the waist portion, and the second disc portion, and the convex bending area and the concave bending area belong to the bending area.

[0017] In some embodiments, a sixth straight area is formed in the middle of the distal end of the first disc portion, a third convex bending area is formed on the outer side of the first disc portion, the distal end of the third convex bending area is connected to the sixth straight area, the proximal end of the third convex bending area is connected to the outer end of the seventh straight area, the inner end of the seventh straight area is connected to the distal end of the third concave bending area, and the proximal end of the third concave bending area is connected to the distal end of the eighth straight area of ​​the waist; and a ninth straight area is formed in the middle of the proximal end of the second disc portion, a fourth convex bending area is formed on the outer side of the second disc portion, the proximal end of the fourth convex bending area is connected to the ninth straight area, the distal end of the fourth convex bending area is connected to the outer end of the tenth straight area, the inner end of the tenth straight area is connected to the proximal end of the fourth concave bending area, and the fourth The distal end of the concave bending area is connected to the proximal end of the eighth straight area of ​​the waist; wherein, it extends outward from the distal end of the third convex bending area to the middle of the third convex bending area, and extends inward from the middle of the third convex bending area to the proximal end of the third convex bending area, so that the third convex bending area forms a bulge from the inside to the outside; it extends outward from the proximal end of the fourth convex bending area to the middle of the fourth convex bending area, and extends inward from the middle of the fourth convex bending area to the distal end of the fourth convex bending area, so that the fourth convex bending area forms a bulge from the inside to the outside, and an inwardly concave corner is formed from the distal end of the third concave bending area to the proximal end of the third concave bending area; an inwardly concave corner is formed from the proximal end of the fourth concave bending area to the distal end of the fourth concave bending area.

[0018] In some embodiments, it includes a first plate portion, a waist portion and a second plate portion which are connected in sequence from far to near, a first convex bending area is formed at the distal end of the first plate portion, a first straight area is formed in the middle of the first plate portion, and a first concave bending area is provided at the connection between the first plate portion and the waist; a second convex bending area is formed at the proximal end of the second plate portion, a second straight area is formed in the middle of the second plate portion, and a second concave bending area is provided at the connection between the second plate portion and the waist, the first concave bending area, the first straight area and the first convex bending area are connected in sequence from near to far, the second convex bending area, the second straight area and the second concave bending area are connected in sequence from near to far, wherein the first convex bending area, the second convex bending area, the first concave bending area and the second concave bending area are the bending areas.

[0019] In some embodiments, the linear expansion coefficients of the first convex bending region and the second convex bending region are greater than those of the first straight region and the second straight region, and the linear expansion coefficients of the first concave bending region and the second concave bending region are less than those of the first straight region and the second straight region.

[0020] In some embodiments, the occluder further includes a fourth straight region and a fifth straight region, the fourth straight region is located at the distal end surface of the occluder, the outer end of the fourth straight region is connected to the distal end of the first convex bending region, the first convex bending region forms a corner outward from the distal end to the proximal end, the proximal end of the first convex bending region is connected to the distal end of the first straight region, the proximal end of the first straight region is connected to the first concave bending region, the first concave bending region extends inward to the waist and then extends to the proximal end; the proximal end of the first concave bending region is connected to the distal end of the third straight region, and the third straight region The proximal end of the domain is connected with the distal end of the second concave bending area; wherein, the second concave bending area starts from the distal end, extends proximally to the proximal end of the second disc portion, and then turns and extends radially outward, the proximal end of the second concave bending area is connected with the distal end of the second straight area, the second straight area extends along the axial direction, and the proximal end of the second straight area is connected with the distal end of the second convex bending area, the proximal end of the second convex bending area bends inwardly toward the fifth straight area, the proximal end of the second convex bending area is connected with the outer end of the fifth straight area, and the fifth straight area is located on the proximal surface of the occluder.

[0021] In some embodiments, the linear expansion coefficient of the flat region is αL 0 The linear expansion coefficient of the convex bending area is αL 1 The linear expansion coefficient of the concave bending area is αL2 The linear expansion coefficient relationship between the convex bending area, the concave bending area and the straight area satisfies αL 1 >αL 0 >αL 2 , wherein the convex bending area includes the first convex bending area and the second convex bending area, and the concave bending area includes the first concave bending area and the second concave bending area; the straight area includes the first straight area, the second straight area, the third straight area, the fourth straight area and the fifth straight area.

[0022] In a second aspect, the present disclosure provides a method for preparing the occluder according to the first aspect, comprising the following steps:

[0023] Using biodegradable materials to prepare block copolymers;

[0024] Prepare a monofilament having bent regions and straight regions;

[0025] The temperature is raised to a temperature not less than the glass transition temperature of the polymer material in the bending region, and forces perpendicular to the axial direction, radially outward and inward are simultaneously applied to the bending region of the monofilament, so that the monofilament is bent into the arc required by the designed shape of the occluder;

[0026] The temperature is lowered to a temperature not higher than the glass transition temperature of the polymer material in the bending area, and the applied mechanical force is released, so that the monofilament is fixed into the designed shape;

[0027] When the temperature is below the glass transition temperature, the monofilaments are woven into an occluder, and after the weaving is completed, the occluder returns to the designed shape.

[0028] In some embodiments, the glass transition temperature is -40°C-80°C; the temperature when the monofilament is woven into the occluder is 25°C-45°C; and the temperature at which the occluder returns to the designed shape is 20°C-40°C.

[0029] In a third aspect, the present disclosure provides a method for preparing the occluder according to the first aspect,

[0030] The monofilament with a bending area and a straight area is woven layer by layer from one end of the occluder to the other end to obtain the occluder, and the occluder returns to the designed shape after the weaving is completed; the straight area is composed of the material of the monofilament; the bending area is composed of a material with a different expansion coefficient from the material of the monofilament; the linear expansion coefficient of the straight area is αL 0 The linear expansion coefficient of the convex bending area is αL 1 The linear expansion coefficient of the concave bending area is αL 2; The connection method of the layer formed by the straight area and the bent area is diamond mesh crochet; The relationship between the linear expansion coefficient of the bent area and the straight area satisfies αL 1 >αL 0 >αL 2 ; The linear expansion coefficient αL1 of the convex bending area is more than 10 times the linear expansion coefficient αL0 of the straight area.

[0031] In some embodiments, the linear expansion coefficient of the convex bending area is αL 1 1.0×10 -3 / ℃~5.0×10 -3 / ℃; the linear expansion coefficient of the flat area αL 0 1.0×10 -5 / ℃~1.0×10 -4 / ℃; the linear expansion coefficient of the concave bending area αL 2 1.0×10 -5 / ℃~1.0×10 -4 / ℃; the linear expansion coefficient of the convex bending area αL 1 αL is the linear expansion coefficient of the flat area 0 The temperature at which the occluder returns to its designed form is 20°C-40°C.

[0032] The degradable occluder prepared by the present invention can restore the designed shape at a predetermined temperature (for example, 37°C or a temperature close thereto), has a shape memory function, simplifies the locking structure of the existing occluder and the locking steps during the occluder implantation process. The occluder preparation process does not require high-temperature shaping, which reduces energy consumption. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 It is a cross-sectional schematic diagram of a part of the structure of the occluder in a certain embodiment of the present disclosure.

[0034] Figure 2 It is a cross-sectional view of an occluder in a certain embodiment of the present disclosure.

[0035] Figure 3 It is a schematic diagram of the partial structure of a monofilament in a certain embodiment of the present disclosure.

[0036] Figure 4 It is a side view schematic diagram of an occluder in another embodiment of the present disclosure.

[0037] Figure 5 for Figure 4 Schematic diagram of the structure of the occluder.

[0038] Figure 6 It is a cross-sectional view of an occluder in another embodiment of the present disclosure.

[0039] Figure 7 It is a cross-sectional view of an occluder in another embodiment of the present disclosure.

[0040] Figure 8 It is a cross-sectional schematic diagram of a part of the structure of the occluder in another embodiment of the present disclosure.

[0041] Markings in the figure: 100, first plate portion; 110, first convex bending area; 120, first straight area; 130, first concave bending area; 140, fourth straight area; 200, waist; 210, third straight area; 300, second plate portion; 310, second convex bending area; 320, second straight area; 330, second concave bending area; 340, fifth straight area; 410, sixth straight area; 420, third convex bending area; 430, seventh straight area; 510, third concave bending area; 520, eighth straight area; 530, fourth concave bending area; 610, ninth straight area; 620, fourth convex bending area; 630, tenth straight area; A, first direction. DETAILED DESCRIPTION

[0042] To make the present disclosure more obvious and easy to understand, the technical solution of the present disclosure is further described below through specific embodiments, which do not limit the protection scope of the present disclosure. Some non-essential modifications and adjustments made by others based on the concept of the present disclosure are still protected by the present disclosure.

[0043] The occluder provided by the present disclosure includes a first disc portion 100, a waist portion 200 and a second disc portion 300 which are connected in sequence from far to near, a sixth straight area 410 is formed in the middle of the distal end of the first disc portion 100, a third convex bent area 420 is formed on the outer side of the first disc portion 100, the distal end of the third convex bent area 420 is connected to the sixth straight area 410, the proximal end of the third convex bent area 420 is connected to the outer end of the seventh straight area 430, the inner end of the seventh straight area 430 is connected to the distal end of the third concave bent area 510, and the proximal end of the third concave bent area 510 is connected to the distal end of the eighth straight area 520 of the waist portion 200. A ninth straight region 610 is formed in the middle of the proximal end of the second disc portion 300, and a fourth convex bending region 620 is formed on the outer side of the second disc portion 300. The proximal end of the fourth convex bending region 620 is connected to the ninth straight region 610, the distal end of the fourth convex bending region 620 is connected to the outer end of the tenth straight region 630, the inner end of the tenth straight region 630 is connected to the proximal end of the fourth concave bending region 530, and the distal end of the fourth concave bending region 530 is connected to the proximal end of the eighth straight region 520 of the waist portion 200. Among them, the third convex bending region 420 convexes from the inside to the outside, the fourth convex bending region 620 convexes from the inside to the outside, the third concave bending region 510 is concave from the outside to the inside, and the fourth concave bending region 530 is concave from the outside to the inside.

[0044] Specifically, the third convex bending area 420 extends outward from the distal end to the middle of the third convex bending area 420, and extends inward from the middle of the third convex bending area 420 to the proximal end of the third convex bending area 420, so that the third convex bending area forms a bulge from the inside to the outside. As for the fourth convex bending area 620, it extends outward from the proximal end of the fourth convex bending area 620 to the middle of the fourth convex bending area 620, and extends inward from the middle of the fourth convex bending area 620 to the distal end of the fourth convex bending area 620, so that the fourth convex bending area 620 forms a bulge from the inside to the outside.

[0045] For the third inwardly concave bending area 510, an inwardly concave corner is formed from the distal end of the third inwardly concave bending area 510 to the proximal end of the third inwardly concave bending area 510. For the fourth inwardly concave bending area 530, an inwardly concave corner is formed from the proximal end of the fourth inwardly concave bending area 530 to the distal end of the fourth inwardly concave bending area 530.

[0046] The sixth straight region 410 , the seventh straight region 430 , the ninth straight region 610 , and the tenth straight region 630 are substantially perpendicular to the first direction A. The eighth straight region 520 is substantially parallel to the first direction A. The first direction A points from the proximal end to the distal end.

[0047] The sixth straight region 410, the third convex bending region 420 and the seventh straight region 430 should belong to the first plate portion 100, the ninth straight region 610, the fourth convex bending region 620 and the tenth straight region 630 should belong to the second plate portion 300, and the ninth straight region 610 belongs to the waist portion 200. The third concave bending region 510 should be located between the first plate portion 100 and the waist portion 200, and the fourth concave bending region 530 should be located between the second plate portion 300 and the waist portion 200.

[0048] It should be noted that the sixth straight region 410 roughly forms the disk surface of the first disk portion 100, and the area occupied by it is roughly circular. The third convex bent region 420 surrounds the sixth straight region 410 and constitutes the outer side of the first disk portion 100. Therefore, the sixth straight region 410 should not be simply understood as a line on the disk surface of the first disk portion 100. In addition, the same is true for other structures.

[0049] When designing, the entire occluder can be woven with one or more monofilaments, and then the monofilaments can be marked according to the various regions, and then the monofilaments can be unfolded to know the regions where the monofilaments need to be adjusted. After that, when producing new monofilaments, the material of the monofilaments can be adjusted according to the marked regions so that the corresponding regions have the corresponding materials.

[0050] It should be noted that if the linear expansion coefficients of the bent area and the straight area are similar, then when the bent area is restored to its original shape at a predetermined temperature, the straight area will also be restored, and a considerable pulling force will be provided to the bent area. This may affect the recovery of the bent area, making it impossible for the disc portion (the first disc portion 100 and the second disc portion 300) to completely return to its original shape, ultimately resulting in a poor occlusion effect of the occluder.

[0051] Specifically, the straight region is made of a certain material; the bent region is made of a material with a linear expansion coefficient different from that of the straight region. The linear expansion coefficient of the straight region (including the sixth straight region 410, the seventh straight region 430, the eighth straight region 520, the ninth straight region 610, and the tenth straight region 630) is αL 0 The convex bending area (ie, the third convex bending area 420 and the fourth convex bending area 620) is replaced with a material having a linear expansion coefficient higher than that of the monofilament, and the linear expansion coefficient is αL 1 The concave bending area (i.e., the third concave bending area 510 and the fourth concave bending area 530) is replaced with a material having a linear expansion coefficient smaller than that of the monofilament, and the linear expansion coefficient is αL 2 .

[0052] More specifically, when the temperature rises from room temperature (25°C) to body temperature (37°C), the linear expansion coefficient of the convex bending area (αL 1 >αL 0 ) expands and provides radial outward force, and the linear expansion coefficient is smaller than that of the concave bending area (αL 2 <αL 0 ) provides resistance to radial outward force, so that the occluder can restore the design shape of double discs (first disc part and second disc part) convex outward and waist 200 concave inward after being released from room temperature into the body through the delivery system.

[0053] In addition, the linear expansion coefficient αL of the convex bending area 1 Should be the linear expansion coefficient of the straight area αL 0 More than 10 times, optionally more than 100 times. Specifically, for the occluder, whether the disc can be fully expanded is one of the more critical cores. Therefore, it is necessary to make the linear expansion coefficient of the convex bending area larger, so that the farthest and closest parts of the occluder can be fully expanded as much as possible, so that the disc can block the ventricular septal defect as much as possible. In addition, the third concave bending area 510 at the distal end and the fourth concave bending area 530 at the proximal end deform and protrude outward according to the predetermined plan, which can effectively apply pressure to the heart tissue between the discs, so that the occluder can tightly seal the ventricular septal defect.

[0054] In some embodiments, the linear expansion coefficient αL of the convex bending region (including the third convex bending region 420 and the fourth convex bending region 620) is 1 1.0×10 -3 / ℃~5.0×10 -3 / ℃;

[0055] In some embodiments, the linear expansion coefficient αL of the straight regions (including the sixth straight region 410 , the seventh straight region 430 , the eighth straight region 520 , the ninth straight region 610 , and the tenth straight region 630 ) is 0 1.0×10 -5 / ℃~1.0×10 -4 / ℃;

[0056] In some embodiments, the linear expansion coefficient αL of the concave bending region (including the third concave bending region 510 and the fourth concave bending region 530) is 2 1.0×10 -5 / ℃~1.0×10 -4 / ℃.

[0057] In some embodiments, the convex bending area is arranged at a distance of 0 to 12 mm from the outermost side.

[0058] In some embodiments, the convex bending area is arranged at a distance of 0 to 10 mm inward from the outermost side.

[0059] In some embodiments, the convex bending area is arranged at a distance of 0 to 6 mm inward from the outermost side.

[0060] In some embodiments, the convex bending area is arranged at a distance of 0 to 4 mm inward from the outermost side.

[0061] Specifically, the convex bending area includes a third convex bending area 420 and a fourth convex bending area 620. The third convex bending area 420 should be set at a distance of 0-12mm extending from the outermost side of the occluder to the inner side, that is, the third convex bending area 420 is located at the outermost side of the occluder and the distance of the third convex bending area 420 extending from the outside to the inside is 0-12mm, which can be 0-4mm. The fourth convex bending area 620 should be set at a distance of 0-12mm extending from the outermost side of the occluder to the inner end, that is, the fourth convex bending area 620 is located at the outermost end of the occluder and the distance of the fourth convex bending area 620 extending from the outside to the inside is 0-12mm, which can be 0-4mm.

[0062] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 3 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0063] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 2 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0064] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 1 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0065] Specifically, the concave bending area includes a third concave bending area 510 and a fourth concave bending area 530. The third concave bending area 510 is set at a position extending 0.5 to 3 mm from the concave bending angle between the first disc and the waist to the first disc and the waist, respectively, and can be 0.5 to 1 mm. The fourth concave bending area 530 is set at a position extending 0.5 to 3 mm from the concave bending angle between the second disc and the waist to the second disc and the waist, respectively, and can be 0.5 to 1 mm.

[0066] In some embodiments, each of the straight regions is 0.5-3 mm; in some embodiments, each of the straight regions is 0.5-2 mm; in some embodiments, each of the straight regions is 0.5-1 mm. Specifically, the straight regions include the sixth straight region 410, the seventh straight region 430, the eighth straight region 520, the ninth straight region 610, and the tenth straight region 630. Each straight region is 0.5-3 mm, which means that the sixth straight region 410, the seventh straight region 430, the eighth straight region 520, the ninth straight region 610, and the tenth straight region 630 have a span of 0.5-3 mm in the far and near directions, respectively.

[0067] In addition, it should be noted that Figure 1 and Figure 2 The bending region of the structure shown may also have a material with stimulus responsive properties. Specifically, in some embodiments, the convex bending region (including the third convex bending region 420 and the fourth convex bending region 620) is a block copolymer; the block copolymer includes one or more biodegradable polymer materials selected from poly (L-lactic acid) (i.e., PLLA), poly (glycolic acid), polycaprolactone (i.e., PCL), poly (p-dioxanone), lactic acid-glycolic acid copolymer or poly (lactic acid-glycolic acid copolymer). The molar ratio of poly (L-lactic acid) to polycaprolactone in the block copolymer is 1:1 to 1:3.

[0068] In some embodiments, the straight regions (including the sixth straight region 410, the seventh straight region 430, the eighth straight region 520, the ninth straight region 610, and the tenth straight region 630) do not have stimulus responsiveness, or cannot restore the designed shape under stimulation by temperature, light, or electrical signals; more specifically, the straight regions do not have shape memory capability.

[0069] In some embodiments, the concave bending region (including the third concave bending region 510 and the fourth concave bending region 530) may also have a material with stimulus responsive properties. Specifically, in some embodiments, the concave bending region is a block copolymer; the block copolymer includes one or more biodegradable polymer materials selected from poly (L-lactic acid) (PLLA), poly (glycolic acid), poly (caprolactone) (PCL), poly (dioxanone), lactic acid-glycolic acid copolymer or poly (lactic acid-glycolic acid copolymer). In some embodiments, the molar ratio of poly (L-lactic acid) to poly (caprolactone) in the block copolymer is 1:1 to 1:3.

[0070] In some embodiments of the present disclosure, the key bending region of the monofilament of the occluder is replaced with a material having stimulus-responsive properties, and the monofilament produced by the method is then used for weaving the occluder, so that it can restore the designed shape under stimulation of temperature, light, electricity and other signals. Specifically, the monofilament used for weaving the occluder is made of a block copolymer, the molecular structure of the key bending region of the monofilament is designed, and the straight region that does not need to be bent is still the original material of the monofilament (i.e., a material without shape memory).

[0071] like Figure 2 It is shown that the material of the monofilament is composed of block copolymers as a whole, and the proportion of polymer materials is controlled in the convex bending area (such as the edge of the occluding disc) and the concave bending area (such as the waist 200 of the occluder). When the temperature reaches the glass transition temperature (Tg) of the polymer material in the bending area, the material changes from a glassy state to a soft, rubber-like, highly elastic state. At this time, perpendicular axial, radial outward and inward forces are applied to the convex and concave bending areas of the monofilament at the same time, respectively, so that the monofilament is bent into the arc required by the design shape of the occluder. After cooling or light fixation, the applied force is released and the monofilament is fixed in a bent shape.

[0072] In other embodiments, such as Figure 4 As shown, the occluder includes a first disc portion 100, a waist portion 200 and a second disc portion 300 connected sequentially from far to near. The first disc portion 100 has a first convex bending area 110 formed at the distal end, a first straight area 120 formed in the middle of the first disc portion 100, and a first concave bending area 130 provided at the connection between the first disc portion 100 and the waist portion 200; the second disc portion 300 has a second convex bending area 310 formed at the proximal end, a second straight area 320 formed in the middle of the second disc portion 300, and a second concave bending area 330 provided at the connection between the second disc portion 300 and the waist portion 200; the first concave bending area 130, the first straight area 120 and the first convex bending area 110 are sequentially connected from near to far, and the second convex bending area 310, the second straight area 320 and the second concave bending area 330 are sequentially connected from near to far.

[0073] It should be noted that the above scheme corresponds to Figure 4 and Figure 5 When the occluder is braided, the monofilaments are braided layer by layer from one end to the other end of the occluder. For details, please refer to the description of Example 2.

[0074] In addition, the first convex bending area 110 , the second convex bending area 310 , the first concave bending area 130 and the second concave bending area 330 are bending areas, and the first straight area 120 and the second straight area 320 are straight areas.

[0075] In addition, in other embodiments, the linear expansion coefficients of the first convex bending region 110 and the second convex bending region 310 are greater than those of the first straight region 120 and the second straight region 320, and the linear expansion coefficients of the first concave bending region 130 and the second concave bending region 330 are smaller than those of the first straight region and the second straight region.

[0076] It should be specifically explained that the first concave bending area 130 spans the first plate portion 100 and the waist portion 200, and the second concave bending area 330 spans the second plate portion 300 and the waist portion 200. In addition, a third straight area 210 is also formed in the waist portion 200, and the third straight area 210 is located between the first concave bending area and the second concave bending area 330.

[0077] For ease of understanding, the present disclosure is marked with a first direction A in the drawings, and the first direction A points from the proximal end to the distal end.

[0078] More specifically, if Figure 8 As shown, the occluder also includes a fourth straight area 140 and a fifth straight area 340. The fourth straight area 140 is located at the distal surface of the occluder (in some embodiments, the fourth straight area 140 is the distal disk surface of the occluder), the outer end of the fourth straight area 140 is connected to the distal end of the first convex bending area 110, the first convex bending area 110 forms an outwardly protruding corner from the distal end to the proximal end, the proximal end of the first convex bending area 110 is connected to the distal end of the first straight area 120, the proximal end of the first straight area 120 is connected to the first concave bending area 130, the first straight area 120 extends in the opposite direction of the first direction A, the distal end of the first concave bending area 130 is located at the proximal end of the first disk portion, then the first concave bending area 130 extends inwardly to the waist 200, and then extends to the proximal end, forming as shown in FIG. Figure 8 The proximal end of the first concave bending area 130 is connected to the distal end of the third straight area 210 , and the proximal end of the third straight area 210 is connected to the distal end of the second concave bending area 330 . Among them, the second concave bending area 330 starts from the distal end, extends proximally to the proximal end of the second disk portion 300, then turns and extends radially outward, the proximal end of the second concave bending area 330 is connected to the distal end of the second straight area 320, the second straight area 320 extends in the opposite direction of the first direction A, and finally the proximal end of the second straight area 320 is connected to the distal end of the second convex bending area 310, the proximal end of the second convex bending area 310 bends inward toward the fifth straight area 340, the proximal end of the second convex bending area 310 is connected to the radially outer side of the fifth straight area 340, and the fifth straight area 340 is located on the proximal surface of the occluder (in some embodiments, the fifth straight area 340 is the proximal disk surface of the occluder).

[0079] It should be noted that Figure 4 Only a side view of the occluder is shown, not a cross-sectional view thereof, so the fourth straight region 140 and the fifth straight region 340 located inside cannot be seen. Figure 6-8 , which shows a cross-sectional view of an occluder in another embodiment. Figure 1 and Figure 2 The structure shown is different in that the first convex bending area 110 only covers the distal surface of the first disc portion 100 and extends a portion toward the proximal end, and does not extend from the distal end of the first disc portion 100 to the proximal end of the first disc portion 100 .

[0080] Specifically, the straight region is made of a certain material; the bent region is made of a material with a linear expansion coefficient different from that of the material used in the straight region. The linear expansion coefficient of the straight region (including the first straight region 120, the second straight region 320, the third straight region 210, the fourth straight region 140 and the fifth straight region 340) is αL 0 The convex bending area (i.e., the first convex bending area 110 and the second convex bending area 310) is replaced with a material having a linear expansion coefficient higher than that of the monofilament, and the linear expansion coefficient is αL 1 The concave bending area (i.e., the first concave bending area 130 and the second concave bending area 330) is replaced with a material having a linear expansion coefficient smaller than that of the monofilament, and the linear expansion coefficient is αL 2 .

[0081] More specifically, when the temperature rises from room temperature (25°C) to body temperature (37°C), the linear expansion coefficient of the convex bending area (αL 1 >αL 0 ) expands and provides radial outward force, and the linear expansion coefficient is smaller than that of the concave bending area (αL 2 <αL 0 ) provides resistance to radial outward force, so that the occluder can restore the design shape of double disc convex and waist 200 concave after being released from room temperature into the body through the delivery system.

[0082] In addition, the linear expansion coefficient αL of the convex bending area 1 Should be the linear expansion coefficient of the straight area αL 0More than 10 times of that. Specifically, for the occluder, whether the disc can be fully expanded is one of the more critical cores. Therefore, it is necessary to make the linear expansion coefficient of the convex bending area larger so that the farthest and closest parts of the occluder can be fully expanded as much as possible, so that the disc can block the ventricular septal defect as much as possible. In addition, the first convex bending area 110 at the distal end and the second convex bending area 310 at the proximal end deform and protrude outward according to the predetermined plan, which can effectively apply pressure to the heart tissue between the discs, so that the occluder can tightly seal the ventricular septal defect.

[0083] In some embodiments, the linear expansion coefficient αL of the convex bending region (including the first convex bending region 110 and the second convex bending region 310) is 1 1.0×10 -3 / ℃~5.0×10 -3 / ℃.

[0084] In some embodiments, the linear expansion coefficient αL of the straight region (including the first straight region 120, the second straight region 320, and the third straight region 210) is 0 1.0×10 -5 / ℃~1.0×10 -4 / ℃.

[0085] In some embodiments, the linear expansion coefficient αL of the concave bending region (including the first concave bending region 130 and the second concave bending region 330) is 2 1.0×10 -5 / ℃~1.0×10 -4 / ℃.

[0086] In some embodiments, the convex bending area is arranged at a distance of 0 to 12 mm from the outermost side.

[0087] In some embodiments, the convex bending area is arranged at a distance of 0 to 10 mm inward from the outermost side.

[0088] In some embodiments, the convex bending area is arranged at a distance of 0 to 6 mm inward from the outermost side.

[0089] In some embodiments, the convex bending area is arranged at a distance of 0 to 4 mm inward from the outermost side.

[0090] Specifically, the convex bending area includes a first convex bending area 110 and a second convex bending area 310. The first convex bending area 110 should be set at a distance of 0-12mm extending from the outermost side of the occluder to the inner side, that is, the first convex bending area 110 is located at the outermost side of the occluder and the distance of the first convex bending area 110 extending from the far side to the near side is 0-12mm, which can be 0-4mm. The second convex bending area 310 should be set at a distance of 0-12mm extending from the outermost side of the occluder to the inner side, that is, the second convex bending area 310 is located at the outermost end of the occluder and the distance of the second convex bending area 310 extending from the outside to the inside is 0-12mm, which can be 0-4mm.

[0091] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 3 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0092] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 2 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0093] In some embodiments, the concave bending area is arranged at a position extending 0.5 to 1 mm from the corner between the disc portion and the waist portion toward the disc portion and the waist portion respectively.

[0094] Specifically, the concave bending area includes a first concave bending area 130 and a second concave bending area 330. The first concave bending area 130 is set at a position extending 0.5 to 3 mm from the concave bending angle between the first disc and the waist to the first disc and the waist, respectively, and can be 0.5 to 1 mm. The second concave bending area 330 is set at a position extending 0.5 to 3 mm from the concave bending angle between the second disc and the waist to the second disc and the waist, respectively, and can be 0.5 to 1 mm.

[0095] In some embodiments, each of the straight regions is 0.5-3 mm; in some embodiments, each of the straight regions is 0.5-2 mm; in some embodiments, each of the straight regions is 0.5-1 mm. Specifically, the straight regions include a first straight region, a second straight region, a third straight region, a fourth straight region, and a fifth straight region, and each of the straight regions is 0.5-3 mm, which means that the span of the first straight region, the second straight region, the third straight region, the fourth straight region, and the fifth straight region in the far and near directions is 0.5-3 mm, respectively.

[0096] Example 1

[0097] 1 mmol CAC (4,4'-(adipoyl)dioxydicinnamic acid), 0.5 mmol PLLA, 0.5 mmol PCL and 15 ml diphenyl ether were mixed and heated at 180°C for 2 hours with stirring. The mixture was poured into 100 ml of 4°C hexane to precipitate PLLA / PCL (molar ratio 50 / 50) block copolymer. When preparing monofilaments by extrusion process, PLLA and PLLA / PCL (50 / 50) block copolymer melted at 180°C were prepared according to Figure 3 As shown, when the bending area is extruded, the hopper contains PLLA / PCL (50 / 50) block copolymer, and when the straight area is extruded, the hopper contains PLLA. At a temperature of 50°C (block copolymer Tg), force is applied to the PLLA / PCL bending area of ​​the monofilament, and forces perpendicular to the axial direction, radially outward and inward are applied to the convex bending area and the concave bending area of ​​the monofilament respectively, so that multiple monofilaments are bent into the designed shape of the occluder, and the temperature is reduced to 25°C to fix it. When weaving the occluder, the temperature of the monofilament should be lower than the Tg of the block copolymer (lower than 50°C) to prevent the bending shape from being changed by force again. After weaving, the occluder is stored at 25°C. Among them, PLLA is left-handed polylactic acid. PCL is polycaprolactone. It should be noted that before PLLA is modified with PCL, PLLA has Tg, but it does not have stimulus response properties, that is, it cannot remember a specific shape when the temperature is higher than Tg. The final shape after weaving can be as follows Figure 1 shown.

[0098] It should be noted that when the monofilament is prepared by the extrusion process, a twin-screw extruder is used. When making the monofilament disclosed in the present invention, the user can add materials in batches. For example, when preparing the bending area, PLLA / PCL (50 / 50) block copolymer is added to the twin-screw extruder, and when preparing the straight area, PLLA is added to the twin-screw extruder. The monofilament can be understood as a linear structure, but due to the material, part or all of its area has the ability of shape memory.

[0099] Furthermore, the monofilament is bent into the design shape of the occluder, and is prepared by a vacuum heat treatment furnace. Specifically, the user first puts the monofilament into a mold, and then heats it through a vacuum heat treatment furnace to bend the monofilament into a predetermined shape. Finally, multiple monofilaments are assembled into an occluder. In some embodiments, multiple monofilaments are arranged around the axis of the occluder to form an occluder, and the corresponding bending areas and straight areas of the multiple monofilaments should be roughly in the same plane perpendicular to the first direction. For example, the third convex bending area of ​​each monofilament is located on the same plane perpendicular to the first direction.

[0100] Furthermore, the monofilament with shape memory is used for weaving the occluder. If the temperature is higher than Tg, the monofilament will form a new bending shape, and the shape of the occluder will change. After the overall weaving of the occluder is completed, the temperature returns to room temperature, and each monofilament is bent according to the designed shape to restore the occluder to the designed shape. Taking the PLLA / PCL (50 / 50) block copolymer in the hopper when the bending area is extruded in Example 1 as an example, the Tg of the block copolymer is 50°C. Therefore, when the temperature is higher than 50°C, the line structure (such as a monofilament) prepared by the PLLA / PCL (50 / 50) block copolymer can be bent under the action of an external force. When the temperature gradually cools down to below 50°C, the above-mentioned line structure will remember the above-mentioned bending situation and remain in the corresponding shape. It should be noted that when the temperature rises but is lower than Tg, the molecular structure of the folded segment of the monofilament tends to be ordered from disorder, the molecular chain is straightened, and the monofilament is straightened as a whole, which is easy to weave the occluder. Therefore, when weaving the occluder, the temperature of the monofilament can be raised to 45°C before weaving. After the overall weaving of the occluder is completed, the temperature returns to room temperature, and the monofilament is folded according to the designed shape, so that the occluder returns to the designed shape.

[0101] It should be noted that PLLA / PCL (50 / 50) is a polymer material in one of the embodiments. In the step of heating the polymer material to a temperature not less than the glass transition temperature of the bending area, applying forces perpendicular to the axial direction, radially outward and inward to the convex bending area and the concave bending area of ​​the monofilament respectively, so that the monofilament is bent into the arc required by the design shape of the occluder; the glass transition temperature of the polymer material is -40℃-80℃, and the glass transition temperature can be selected as 50℃-60℃. Specifically, first of all, if the glass transition temperature is too high, it will not be much different from the current high-temperature shaping method, which is easy to cause energy waste during the shaping process. Secondly, the glass transition temperature of the polymer material should not be higher than the melting point of the polymer material.

[0102] Example 2

[0103] like Figure 8 As shown, the convex bending area of ​​the occluder woven from monofilament is set at the outermost side and the distance inward is 1 / 3 of the diameter of the occluder disc, and the concave bending area is set at the angle between the disc and the waist 200 of the occluder, 1mm away from the disc and the waist 200, and the total length is 2mm, and the straight area of ​​the waist 200 of the occluder is 2mm. Figure 4 as well as Figure 5 The occluder is woven layer by layer from one end to the other, and the connection between the straight area and the bending area is a diamond mesh hook. When weaving an occluder with a diameter of 18 mm, the convex bending area is 0-6 mm inward from the outermost side, and the linear expansion coefficient is 3.5×10 -3 / ℃ polypropylene carbonate (PPC) material, the linear expansion coefficient of the flat area is 7.5×10-5 / ℃ PLLA material, the concave bending area uses a linear expansion coefficient of 3.8×10 -5 / ℃ PLLA material. The braided occluder is stored at 4℃, and the temperature rises to body temperature 37℃ during the implantation process, ∆T=33℃. When it reaches the implantation site, the convex bending area expands radially outward due to the temperature increase. After expansion, the length of the convex bending area is 6.693mm, and the diameter of the disc increases by 1.386mm, providing a radial outward force to restore the disc of the occluder to the expected double disc shape. When the temperature rises to body temperature, the lengths of the concave bending area and the straight area after expansion are 2.0025mm and 2.005mm respectively, which are almost not expanded compared to the convex bending area, providing a force to resist the radial outward expansion of the disc, so that the occluder returns to the shape of double disc bending convex, the waist 200 and the disc corner are concave, and the shape of the waist 200 remains unchanged.

[0104] It should be noted that the diamond mesh is crocheted as Figure 5 As shown, the monofilaments of the convex bending area (including the first convex bending area 110 and the second convex bending area 310), the concave bending area (including the first concave bending area 130 and the second concave bending area 330) and the straight area (including the first straight area 120, the second straight area 320 and the third straight area 210) respectively form a multi-layer mesh structure similar to a rhombus, but the mesh structures of each layer are hooked together through one of the corners of the rhombus. That is, when weaving, the monofilaments are allowed to pass through one of the corners of the adjacent layers. In some examples, the first convex bending area 110 can be woven first, that is, the first convex bending area 110 with one or more layers of rhombus mesh can be woven, and then, when weaving the first straight area 120, the first straight area can be allowed to pass through the corner of the rhombus mesh of the adjacent first convex bending area 110, so that the rhombus mesh in the first straight area 120 and the rhombus mesh in the first convex bending area are hooked together. Then, the remaining regions are woven in sequence (the first concave bending region 130, the third straight region 210, the second concave bending region 330, the second straight region 320, and the second convex bending region 310, etc.) to form an occluder. The occluder woven layer by layer in the above manner has a good linear expansion coefficient because the farthest end and the proximal end use the first convex bending region 110 and the second convex bending region 310 respectively, so it can expand more significantly, provide radial outward force, and restore the occluder disc to the expected double disc shape.

[0105] It should be noted that, due to the large linear expansion coefficient of the convex bending area, if the extrusion process in Example 1 is used to obtain or form the device, it may expand too much during forming, making it difficult to handle later. In addition, the occluder prepared by layer-by-layer weaving is relatively easier to expand, which is conducive to forming the desired double-disc shape.

[0106] In addition, the present disclosure can optimize or reduce the buckles of the degradable occluder, making the operation more convenient.

[0107] The above-mentioned embodiments are only preferred embodiments of the present disclosure and cannot be used to limit the scope of protection of the present disclosure. Any non-substantial changes and substitutions made by technicians in this field on the basis of the present disclosure shall fall within the scope of protection required by the present disclosure.

Claims

1. A method for preparing an occluder, characterized in that: include: The monofilaments with bent areas and straight areas are braided layer by layer from one end of the occluder to the other end to obtain the occluder, and after the braiding is completed, the occluder returns to the designed shape; The straight area is composed of a monofilament material; the linear expansion coefficient of the straight area is αL0, the bending area includes a convex bending area and a concave bending area, the linear expansion coefficient of the convex bending area is αL1, and the linear expansion coefficient of the concave bending area is αL2; the connection method of the layer formed by the straight area and the bending area is diamond mesh crochet; the relationship between the linear expansion coefficients of the bending area and the straight area satisfies αL1>αL0>αL2; the linear expansion coefficient αL1 of the convex bending area is more than 10 times the linear expansion coefficient αL0 of the straight area; The occluder includes the bending area and the straight area connected to each other, and the bending area is made of a material having a linear expansion coefficient different from that of the straight area.

2. The method for preparing the occluder according to claim 1, characterized in that: The linear expansion coefficient αL1 of the convex bending area is 1.0×10 -3 / ℃~5.0×10 -3 / ℃; the linear expansion coefficient αL0 of the straight area is 1.0×10 -5 / ℃~1.0×10 -4 / ℃; the linear expansion coefficient αL2 of the concave bending area is 1.0×10 -5 / ℃~1.0×10 -4 / ℃.

3. The method for preparing the occluder according to claim 1, characterized in that: The material of the monofilament is polypropylene carbonate; the material of the bending area is a block copolymer with poly-L-lactic acid as one of the monomers.

4. The method for preparing the occluder according to claim 1, characterized in that: The diameter of the occluder is 12~36 mm; the convex bending area is set at a distance of 0~12 mm inward from the outermost side; the concave bending area is set at a position extending 0.5~3 mm from the angle between the disc and the waist to the disc and the waist respectively; each straight area is 0.5~3mm.

5. The method for preparing the occluder according to any one of claims 1 to 4, characterized in that: The occluder skeleton comprises a first disc portion, a waist portion and a second disc portion which are sequentially connected from far to near, and a convex bending area and a concave bending area are formed in the first disc portion, the waist portion and the second disc portion.

6. The method for preparing the occluder according to claim 5, characterized in that: A sixth straight area is formed in the middle of the distal end of the first disc portion, a third convex bending area is formed on the outer side of the first disc portion, the distal end of the third convex bending area is connected to the sixth straight area, the proximal end of the third convex bending area is connected to the outer end of the seventh straight area, the inner end of the seventh straight area is connected to the distal end of the third concave bending area, the proximal end of the third concave bending area is connected to the distal end of the eighth straight area of ​​the waist, a ninth straight area is formed in the middle of the proximal end of the second disc portion, a fourth convex bending area is formed on the outer side of the second disc portion, the proximal end of the fourth convex bending area is connected to the ninth straight area, the distal end of the fourth convex bending area is connected to the outer end of the tenth straight area, the inner end of the tenth straight area is connected to the proximal end of the fourth concave bending area, and the fourth concave bending area The distal end of the domain is connected to the proximal end of the eighth straight region of the waist; wherein, it extends outward from the distal end of the third convex bending region to the middle of the third convex bending region, and extends inward from the middle of the third convex bending region to the proximal end of the third convex bending region, so that the third convex bending region forms a bulge from the inside to the outside; it extends outward from the proximal end of the fourth convex bending region to the middle of the fourth convex bending region, and extends inward from the middle of the fourth convex bending region to the distal end of the fourth convex bending region, so that the fourth convex bending region forms a bulge from the inside to the outside, and an inwardly concave corner is formed from the distal end of the third concave bending region to the proximal end of the third concave bending region; an inwardly concave corner is formed from the proximal end of the fourth concave bending region to the distal end of the fourth concave bending region.

7. The method for preparing the occluder according to any one of claims 1 to 4, characterized in that: It includes a first plate portion, a waist portion and a second plate portion which are connected in sequence from far to near, a first convex bending area is formed at the distal end of the first plate portion, a first straight area is formed in the middle of the first plate portion, and a first concave bending area is arranged at the connection between the first plate portion and the waist; a second convex bending area is formed at the proximal end of the second plate portion, a second straight area is formed in the middle of the second plate portion, and a second concave bending area is arranged at the connection between the second plate portion and the waist, the first concave bending area, the first straight area and the first convex bending area are connected in sequence from near to far, the second convex bending area, the second straight area and the second concave bending area are connected in sequence from near to far, wherein the first convex bending area, the second convex bending area, the first concave bending area and the second concave bending area are the bending areas.

8. The method for preparing the occluder according to claim 7, characterized in that: The linear expansion coefficients of the first convex bending area and the second convex bending area are greater than those of the first straight area and the second straight area, and the linear expansion coefficients of the first concave bending area and the second concave bending area are smaller than those of the first straight area and the second straight area.

9. The method for preparing the occluder according to claim 8, characterized in that: The occluder also includes a fourth straight region and a fifth straight region, the fourth straight region is located at the distal end surface of the occluder, the outer end of the fourth straight region is connected to the distal end of the first convex bending region, the first convex bending region forms a corner outward from the distal end to the proximal end, the proximal end of the first convex bending region is connected to the distal end of the first straight region, the proximal end of the first straight region is connected to the first concave bending region, the first concave bending region extends inward to the waist and then extends to the proximal end; the proximal end of the first concave bending region is connected to the distal end of the third straight region, the proximal end of the third straight region Connected with the distal end of the second concave bending area; wherein, the second concave bending area starts from the distal end, extends proximally to the proximal end of the second disc portion, and then turns and extends radially outward, the proximal end of the second concave bending area is connected to the distal end of the second straight area, the second straight area extends along the axial direction, and the proximal end of the second straight area is connected to the distal end of the second convex bending area, the proximal end of the second convex bending area bends inwardly toward the fifth straight area, the proximal end of the second convex bending area is connected to the outer end of the fifth straight area, and the fifth straight area is located on the proximal surface of the occluder.

10. The method for preparing the occluder according to claim 9, characterized in that: The convex bending area includes the first convex bending area and the second convex bending area, and the concave bending area includes the first concave bending area and the second concave bending area; the straight area includes the first straight area, the second straight area, the third straight area, the fourth straight area and the fifth straight area.

11. The method for preparing the occluder according to claim 1, characterized in that: The temperature at which the occluder returns to its designed form is 20°C-40°C.

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