CN111110399B

CN111110399B - Implantable device

Info

Publication number: CN111110399B
Application number: CN201911252658.0A
Authority: CN
Inventors: 褚华磊; 姚斌
Original assignee: Lifetech Scientific Shenzhen Co Ltd
Current assignee: Shenzhen Jianxin Medical Technology Co ltd
Priority date: 2019-12-09
Filing date: 2019-12-09
Publication date: 2021-12-03
Anticipated expiration: 2039-12-09
Also published as: CN111110399A

Abstract

The present invention relates to an implantable device. This implantable device includes apparatus body and degradable fixed line, and the degradable fixed line includes the fixed line body, and the fixed line body has stiff end and free end, stiff end and apparatus body fixed connection, and the free end is used for fixing to organizing on, and the degradation of fixed line body is from stiff end to free end, degrades along the length direction of fixed line body gradually. The implanted device is difficult to shift, and degradation of the degradable fixed line can not generate a large amount of degradation fragments, so that the implanted device is safe to use.

Description

Implantable device

Technical Field

The invention relates to the field of medical instruments, in particular to an implantable instrument.

Background

This section provides background information related to the present disclosure only and is not necessarily prior art.

Minimally invasive interventional medicine is a diagnostic and therapeutic procedure performed by using a series of interventional instruments and materials and modern digital medical devices. At present, minimally invasive interventional medical treatment is rapidly developed due to the advantages of small wound, quick recovery and the like, and the minimally invasive interventional operation range covers the fields of cardiovascular, cerebrovascular, peripheral blood vessels, trachea and the like.

The minimally invasive interventional operation is to implant an implanted device into a corresponding part in a human body by adopting a minimally invasive method so as to carry out corresponding treatment. For example, transcatheter delivery of a heart occluding device into the heart occludes a heart defect, delivery of a heart valve device into the heart to replace a damaged native heart valve, delivery of a stent graft into a blood vessel to isolate an aneurysm from the blood flow, and the like. Whether the implantable device is a temporary implantable device or a permanent implantable device, the implantable device needs to be fixed at a part needing treatment in a service period, the implantable device cannot play a treatment role when being displaced, and is easy to fall off, and the fallen-off implantable device can bring great pain and injury to a patient. To avoid displacement of the instrument, some instruments are also provided with a fixation wire by which the instrument is connected to the tissue. However, although the fixing wire has a certain fixing function, the presence of the fixing wire may also have an adverse effect. For example, after the service life of the instrument is over, the fixation wire remains in the body for a long time, and may cause some damage to the connected tissue. Alternatively, when the heart occluder is fixedly connected to heart tissue by a fixing wire, the presence of the fixing wire may affect the development of the heart for the young child who needs to implant the heart occluder. For patients with mitral valve regurgitation, there is often a degree of cardiac enlargement and symptoms of congestive heart failure due to regurgitation, commonly known as dilated cardiomyopathy. After the artificial valve replacement, the heart can be gradually restored to the original size, the time for restoring to the original size varies from one person to another, generally 1 year to 5 years are needed, and in the process, the length of the fixing line cannot be adjusted along with the size of the heart. Therefore, the fixation line may adversely affect the recovery of the heart to some extent.

Although the degradable fixing thread can solve the above problems, the degradable fixing thread generates a large amount of fragments in the degradation process, and the fragments are randomly dissociated to other parts, thereby generating an uncontrollable risk.

Disclosure of Invention

Based on this, there is a need for an implantable device that is relatively difficult to displace and does not produce significant amounts of degraded debris.

An implantable device, includes the apparatus body, still includes the fixed line of degradable, the fixed line of degradable is including fixed line body, fixed line body has stiff end and free end, the stiff end with apparatus body fixed connection, the free end is used for fixing to organizing on, the degradation of fixed line body is followed the stiff end extremely the free end is followed the length direction of fixed line body degrades gradually.

In one embodiment, the wire diameter of the fixing wire body gradually increases or gradually decreases along the length direction of the fixing wire body from the fixed end to the free end, so that the degradation of the fixing wire body is gradually degraded along the length direction of the fixing wire body from the fixed end to the free end.

In one embodiment, the degradable fixing wire further comprises a control degradation coating covering the surface of the fixing wire body, wherein the control degradation coating is a delay degradation coating, and the degradation of the delay degradation coating is gradually degraded along the length direction of the fixing wire body from the fixed end to the free end, so that the degradation of the fixing wire body is gradually degraded along the length direction of the fixing wire body from the fixed end to the free end.

In one embodiment, the thickness of the degradation-retarding coating gradually increases along the length direction of the fixing wire body from the fixed end to the free end, so that the degradation of the fixing wire body gradually degrades along the length direction of the fixing wire body from the fixed end to the free end.

In one embodiment, the degradation-regulating coating is a degradation-promoting coating, and the degradation rate of the degradation-promoting coating gradually decreases along the length direction of the fixing wire body from the fixed end to the free end, so that the degradation of the fixing wire body gradually degrades along the length direction of the fixing wire body from the fixed end to the free end.

In one embodiment, the material of the degradation-retarding coating is at least one selected from the group consisting of polylactic acid-glycolic acid copolymer, polyglycolic acid, racemic polylactic acid, polycaprolactone, levorotatory polylactic acid, and polyurethane.

In one embodiment, the fixation wire body has a shape memory property such that a length of the fixation wire body in a natural state is less than a length of the fixation wire body in an operational state.

In one embodiment, the fixing wire body is in a spiral shape, a mosquito coil shape or an irregular shape in a natural state.

In one embodiment, the height of the fixing wire body is less than 5mm in a natural state.

In one embodiment, the material of the fixing thread body is polycaprolactone-based shape memory material, levorotatory polylactic acid-based shape memory material, polyurethane-based shape memory material, polylactic acid-glycolic acid copolymer-based shape memory material, or poly-p-dioxanone-based shape memory material.

In one embodiment, the wire diameter of the fixing wire body is 0.1-4.0 mm.

In one embodiment, the implantable device further comprises a non-degradable fixation wire connected to a free end of the degradable fixation wire.

The implantable device comprises a device body and a degradable fixing wire, wherein the degradable fixing wire is connected with the device body and tissues, so that the implantable device is difficult to displace; moreover, the degradable fixing line is degraded gradually along the length direction of the fixing line body from the fixed end to the free end of the fixing line body, a large amount of degradation fragments can not be generated, and the use is safe.

Drawings

FIG. 1 is a schematic structural view of one embodiment of a heart valve prosthesis;

FIG. 2 is a schematic view of the heart valve prosthesis of FIG. 1 implanted in a heart;

FIG. 3 is a schematic structural view of a fixing wire body according to an embodiment;

FIG. 4 is a schematic structural view of another embodiment of a fixing wire body;

FIG. 5 is a schematic structural view of a fixing wire body according to yet another embodiment;

FIG. 6 is a schematic structural view of a fixing wire body according to yet another embodiment;

fig. 7 is a schematic view illustrating connection of a degradable securing line and a non-degradable securing line in one embodiment.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather should be construed as broadly as the present invention is capable of modification in various respects, all without departing from the spirit and scope of the present invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

The implantable device is difficult to displace, does not generate a large amount of degradation fragments, and is safe to use.

An implantable device of an embodiment includes a device body and a degradable securing wire. The degradable fixing line comprises a fixing line body, the fixing line body is provided with a fixed end and a free end, the fixed end is fixedly connected with the instrument body, and the free end is used for being fixed to tissues.

In a specific embodiment, the wire diameter of the fixing wire body gradually increases or gradually decreases along the length direction of the fixing wire body from the fixed end to the free end.

In a specific embodiment, the degradable fixing wire further comprises a controlled degradation coating, and the controlled degradation coating covers the surface of the fixing wire body. The degradation control coating is a degradation delay coating. From the fixed end to the free end, the thickness of the degradation-delaying coating gradually increases along the length direction of the fixed line body.

In a specific embodiment, the degradation characteristics of the material of the degradation-retarding coating are different along the length of the fixation wire body from the fixed end to the free end.

The implantable device is described in detail below with reference to a heart valve prosthesis as an example. It should be noted that the implantable device is not limited to a heart valve prosthesis, and any device that requires fixation with a fixation wire, such as a heart occluder, is suitable.

Referring to fig. 1, one embodiment of a heart valve prosthesis 100 includes an instrument body 110 and a degradable securing wire 120. One end of the degradable fixing wire 120 is fixedly connected with the device body 110, and the other end is used for connecting with tissue (such as apical tissue) to avoid the device body 110 from being displaced.

The degradable securing thread 120 includes a securing thread body 121. The fixed wire body 121 has a fixed end 1211 and a free end 1212. In a natural state (non-implanted and non-compressed state), the fixed end 1211 of the fixed wire body 121 is fixedly connected to the device body 110, and the free end 1212 is a floating end. In the implanted state (working state), the free end 1212 is used to secure to apical tissue (as shown in fig. 2) to avoid displacement of the heart valve prosthesis 100.

It will be appreciated that the fixed end 1211 of the fixation wire body 121 may be fixedly coupled to the instrument body 110 in a manner well within the skill of the art, including but not limited to a snap-fit connection, an adhesive, etc.

The degradation of the fixing wire body 121 is gradually degraded along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212. Compared with disordered degradation or irregular degradation, the gradual degradation mode can avoid the generation of a large amount of degradation fragments, and the use is safe.

It should be noted that the degradation of the fixing wire body 121 refers to degradation in a physiological fluid environment. The physiological fluid environment is a biological fluid environment such as a blood environment or a tissue fluid environment. The environment simulating physiological body fluid is physiological saline, DMEM solution, SBF solution, Hanks solution, PBS solution and the like.

Referring to fig. 3, in one embodiment, the wire diameter of the fixing wire body 121 gradually increases along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212, so that the degradation of the fixing wire body 121 gradually degrades along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212. When the cross section of the fixed wire body 121 is a regular geometric shape, the wire diameter refers to the side length (corresponding to a square), the diameter (corresponding to a circle), the major axis (corresponding to an ellipse), and the like of the regular geometric shape; when the cross-section of the fixing wire body 121 has an irregular geometric shape, the wire diameter refers to the maximum distance between any two points of the cross-section. The above definition of the line diameter is applicable to the whole text, and is not described in detail below.

In another embodiment, the wire diameter of the fixing wire body 121 is gradually reduced along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212, such that the degradation of the fixing wire body 121 is gradually degraded along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212.

It should be noted that the increasing of the wire diameter means a linear increase or a non-linear increase, and the decreasing of the wire diameter means a linear decrease or a non-linear decrease.

In one embodiment, the fixed wire body 121 is a circular truncated cone, and the wire diameter (cross-sectional diameter) of the fixed wire body 121 increases linearly from the upper bottom surface to the lower bottom surface of the circular truncated cone in the longitudinal direction of the fixed wire body 121 by 0.02mm/m to 10 mm/m.

In one embodiment, the fixing wire body 121 is a circular truncated cone, and the wire diameter (cross-sectional diameter) of the fixing wire body 121 increases non-linearly along the length direction of the fixing wire body 121 from the upper bottom surface to the lower bottom surface of the circular truncated cone. The fixed wire body 121 has a wire diameter of 1.000656^L0.9, L is the distance of the current cross section to the upper bottom surface. 1.000656^LThe value of-0.9 is the diameter of the current section. The unit of L is millimeters and the unit of the calculated diameter is also millimeters. I.e., any cross-sectional diameter of the fixed wire body 121 as described above 1.000656^L-0.9 calculation.

It is understood that when the degradable fixation thread 120 includes only the fixation thread body 121, the fixation thread body 121 is the degradable fixation thread 120 itself.

Referring to fig. 4, in one embodiment, the degradable fixing wire 120 further includes a degradation-controlling coating 122, and the degradation-controlling coating 122 covers the surface of the fixing wire body 121.

In one embodiment, the degradation modulating coating 122 is a delayed degradation coating. The degradation delaying coating is coated on the surface of the fixing wire body 121 to play a certain protection role, the degradation delaying coating is firstly degraded to expose the fixing wire body 121, and the subsequent fixing wire body 121 is degraded. The portion of the fixation wire body 121 covered by the area of the preferentially degradable degradation-retarding coating is preferentially exposed and thus preferentially degraded. The degradation of the degradation-retarding coating layer is gradually degraded along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212, thereby gradually exposing the fixing wire body 121, so that the fixing wire body 121 is gradually degraded along the length direction from the fixed end 1211 to the free end 1212.

In one embodiment, the thickness of the degradation-retarding coating gradually increases along the length of the fixing wire body 121 from the fixed end 1211 to the free end 1212, such that the degradation of the degradation-retarding coating gradually degrades along the length of the fixing wire body 121 from the fixed end 1211 to the free end 1212, thereby gradually exposing the fixing wire body 121, and the degradation of the fixing wire body 121 gradually degrades along the length of the fixing wire body 121 from the fixed end 1211 to the free end 1212.

It should be noted that, the thickness of the degradation-retarding coating layer gradually increases along the length direction of the fixing wire body 121, which means a linear increase or a non-linear increase.

In one embodiment, the thickness of the degradation-retarding coating increases linearly along the length of the fixation wire body 121 with an increase of no more than 10mm/cm from the fixed end 1211 to the free end 1212.

In one embodiment, the thickness of the degradation-retarding coating is a x L along the length of the wire body 121 from the fixed end 1211 to the free end 1212²A regular non-linear increase of +0.1, wherein a-22 x 10^-5mm^-1L is the distance from the current section to the bottom surface, a X L²The value of +0.1 is the diameter of the current section.

In one embodiment, the degradation characteristics of the material of the degradation-retarding coating layer are different along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212, such that the degradation-retarding coating layer gradually degrades along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212.

In one embodiment, the regulated degradation coating 122 is a pro-degradation coating. When the degradation promoting coating is degraded, a degradation promoting substance is released to coat the surface of the fixing wire body 121, so as to promote corrosion of the fixing wire body 121. From the fixed end 1211 to the free end 1212, the degradation rate of the degradation promoting coating is gradually reduced along the length direction of the fixing wire body 121 from the fixed end 1211 to the free end 1212, and the higher the degradation rate of the degradation promoting coating is, the faster the degradation promoting substance is released, which is more beneficial to accelerating the corrosion of the fixing wire body 121.

In one embodiment, the fixation wire body 121 has a shape memory property such that the length of the fixation wire body 121 in a natural state is less than the length of the fixation wire body 121 in an operational state. The natural state refers to a state in which the free end 1212 of the fixing wire body 121 is not connected to the tissue, but is suspended. The working state refers to a state in which the free end 1212 of the fixing wire body 121 is connected with the tissue so that the fixing wire body 121 is stretched. Since the fixing wire body 121 has a shape memory property, when the fixed end 1211 of the fixing wire body 121 is disconnected from the instrument body 110 due to degradation, the stretched state is released, and the fixing wire body 121 is restored to the shape in the natural state. The length of the fixing wire body 121 in the natural state is smaller than the length of the fixing wire body 121 in the working state, so that after the fixed end 1211 of the fixing wire body 121 is disconnected from the device body 110, the length is shortened, and the free end 1212 of the fixing wire body 121 is prevented from interfering with other tissues, for example, after the fixing wire body 121 is broken, the fixed end 1211 enters the left atrium, and the mitral valve insufficiency is prevented from regurgitating.

Referring to fig. 5, in one embodiment, the fixing wire body 121 is a spiral shape in a natural state.

In one embodiment, the height of the helical fixation wire body 121 is less than 5mm in the natural state to avoid interference of the free end 1212 with other tissue.

In one embodiment, as shown in fig. 6, the fixing wire body 121 is shaped like a mosquito coil in a natural state. After the mosquito coil-shaped fixing wire body 121 is restored to the natural state, the height of the fixing wire body 121 is substantially the same as the wire diameter of the fixing wire body 121, so as to prevent the free end 1212 from interfering with other tissues.

In one embodiment, the fixed wire body 121 is irregularly shaped. Regardless of the shape of the fixing wire body 121, the length of the fixing wire body 121 in a natural state is smaller than the length of the fixing wire body 121 in an operating state.

In one embodiment, the material of the fixing wire body 121 is a polycaprolactone-based shape memory material, a levopolylactic acid-based shape memory material, a polyurethane-based shape memory material, a polylactic acid-glycolic acid copolymer-based shape memory material, or a poly-p-dioxanone-based shape memory material.

The material is a degradable shape memory material with good biocompatibility, and the degradation product is friendly to organisms.

In one embodiment, the polycaprolactone-based shape memory material is a copolymer of polycaprolactone, a diisocyanate, and ethylene glycol. Wherein the molar ratio of the sum of the molar amounts of the diisocyanate and the ethylene glycol to the molar amount of the polycaprolactone is 6:1, and the molar ratio of the diisocyanate and the ethylene glycol is 3: 2.

In one embodiment, the L-polylactic acid-based shape memory material is a composite of L-polylactic acid and chitosan, wherein the mass fraction of chitosan is 15%.

After the heart valve prosthesis 100 is implanted into a corresponding position and the free ends 1212 of the degradable fixing wires 120 are fixed to heart tissue, the degradable fixing wires 120 generate a certain pulling force to the heart valve prosthesis 100 to ensure that the heart valve prosthesis 100 is fixed at a preset position, so that the heart valve prosthesis 100 can be displaced. Therefore, the degradable securing thread 120 must have sufficient strength to avoid being prematurely pulled apart. Therefore, the diameter of the degradable fixing thread 120 is not too small. However, when the diameter of the degradable fixing thread 120 is too large, the degradable fixing thread 120 is degraded and broken for too long, which may cause the degradable fixing thread 120 to generate continuous pulling force on the device body 110 after completing endothelialization, and at this time, it may cause the device body 110 to deviate from the predetermined position or cause tissue damage. Therefore, the diameter of the degradable fixing thread 120 should not be too large. In one embodiment, the degradable fixing thread 120 has a thread diameter of 0.1-4.0 mm, which is beneficial to ensure sufficient strength and proper degradation period. In one embodiment, the diameter of the degradable fixing thread 120 is 0.1-0.7 mm, so that the degradation period of the degradable fixing thread 120 is shorter.

Meanwhile, when the degradation rate of the degradable fastening thread 120 itself is too fast, the fixed end 1211 and the device body 110 may be prematurely detached due to premature degradation and breakage of the degradable fastening thread 120. Should degrade and release after endothelialization is complete, otherwise it is difficult to achieve the effect of preventing the heart valve prosthesis 100 from dislodging. When the degradation rate of the degradable fixing thread 120 itself is slow, the time for the degradable fixing thread 120 to be degraded and broken is excessively long. Therefore, the degradation rate of the degradable securing thread 120 should be moderate. In one embodiment, the weight-average molecular weight of the material of the fixing wire body 121 is 10 to 300KDa, the polydispersity is 1 to 3, and the crystallinity is 30 to 60%.

Referring again to fig. 2, in one embodiment, the heart valve prosthesis 100 further includes a spacer 130. In securing the free end 1212 to tissue, the free end 1212 is first passed through tissue (e.g., apical tissue) and the pad 130 in sequence, the pad 130 is conformed to the tissue, and then the free end 1212 is knotted to achieve a secure connection. The gasket 130 plays a role in fixation, which is beneficial to preventing the degradable fixing thread 120 from falling off from the tissue; on the other hand, the gasket 130 acts as a seal to prevent blood leakage at the tissue opening.

In one embodiment, an endothelialization promoting coating is disposed on a surface of the gasket 130 opposite to the tissue, and the endothelialization promoting coating can rapidly promote endothelial cells to climb on the surface of the gasket 130, so as to prevent the gasket 130 from falling off after the degradable fixing wire 120 is broken, thereby improving the safety of use.

The preparation of the degradable fixing thread 120 includes the following steps:

step 110: a fixing wire body 121 is provided.

In one embodiment, the fixing wire body 121 is prepared by a 3D printing method. Firstly, drying the polymer material at the drying temperature of 60-120 ℃ for 2-8 h. The dried polymer material was then poured into the material feeder of the 3D printer. Furthermore, a three-dimensional solid model of the fixed line body is drawn by utilizing UG, Solidworks or Pro-E and other three-dimensional design software, and is stored in a stl format and imported into slicing software. In order to ensure that the printed fixed line body has higher mechanical strength and integrity, the printing filling density, the printing temperature, the printing speed and other process parameters are controlled to be appropriate, so that the printing temperature is controlled to be 170-250 ℃, the printing filling density is controlled to be 50-90%, and the printing speed is controlled to be 70-140 mm/s.

The irregular fixing line body 121 is conveniently prepared by a 3D printing method.

In one embodiment, the fixing wire body 121 is formed by 3D printing, and the fixing wire body 121 is divided into a plurality of sections, each of which has a different crystallinity, such that the fixing wire body 121 is gradually degraded from the fixed end 1211 to the free end 1212 along the length direction of the fixing wire body 121.

Step 120: a controlled degradation coating 122 is formed on the surface of the fixed wire body 121.

When the degradable fixing thread 120 includes only the fixing thread body 121, the regulated degradation coating 122 does not need to be prepared again.

When the degradable fixing thread 120 further includes the degradation-controlling coating 122, the degradation-controlling coating is formed by spraying or leaching, etc.

When the spraying method is adopted, firstly, degradable high polymer materials are dissolved in a solvent to prepare a solution with the concentration of 1 mg/mL-saturation, a shelter such as a PLLA plate, a NiTi plate, a stainless steel plate and the like is used for sheltering the fixed wire body before spraying, after the spraying is started, the shelter is slowly drawn out (or the shelter is rotated to slowly expose the fixed wire body), and the drawing speed is not less than 0.1 mm/min. After the spraying is finished and the drying is carried out, the control degradation coating 122 with uneven thickness is formed on the surface of the fixing wire body 121.

When the leaching method is adopted, the fixing wire body 121 is immersed in the leaching solution, one end of the fixing wire body 121 is lifted, and the fixing wire body 121 is slowly lifted out of the leaching solution. And after the fixing wire body 121 completely leaves the leaching liquor, drying to obtain the degradable fixing wire 120 with the thickness gradually increased from the far end to the near end to regulate the degradation coating 122. Wherein the speed of extracting the fixing wire body 121 from the leaching solution should be more than 0.1 mm/min.

Step 130: and (5) shaping the sprayed fixing line body 121.

The sizing process is performed to give the fixing wire body 121 an initial shape such that the length of the fixing wire body 121 in a natural state is smaller than the length of the fixing wire body 121 in an operating state. For example, the fixing thread body 121 is formed into a spiral shape, a mosquito coil shape, or an irregular shape by performing a setting process.

In one embodiment, the shaping is performed using a heat treatment. The setting temperature should be above the glass transition temperature (Tg) of the polymer. And, in order to ensure the shape after the shaping, the shaping time should not be less than 2 min.

In one embodiment, the sprayed fixing wire body 121 is wound around a mold rod with an outer diameter of 2cm, the mold rod is coated with 3 to 5 layers of PTFE films in advance, and after the fixing wire body 121 is wound, 3 layers of PTFE films are coated, wherein the 3 layers of PTFE films completely cover the fixing wire body 121. Then, heat treatment is performed for 2 to 20min at a temperature higher than the Tg of the fixed wire body 121.

Referring to fig. 7, in one embodiment, the heart valve prosthesis 100 further includes a non-degradable fixing wire 140, and the non-degradable fixing wire 140 is connected to the free end of the degradable fixing wire 120. The non-degradable fixation thread 140 is connected to the degradable fixation thread 120 to form an integrated fixation thread to connect the heart valve prosthesis 100 to tissue. When the degradable securing thread 120 is degraded, the connection of the heart valve prosthesis 100 and the tissue is broken, which can avoid adversely affecting the patient's heart recovery. When the implantable device is a heart plugging device, adverse effects on the development of the heart of the infant can be avoided. Moreover, due to the arrangement of the non-degradable fixing thread 140, the degradable fixing thread 120 with a shorter length can be used, which is beneficial to reducing the generation of fragments on the one hand and reducing degradation products on the other hand, so as to avoid tissue inflammation.

When heart valve prosthesis 100 further includes non-degradable fixation wire 140, degradable fixation wire 120 is used as a portion that is connected to heart valve prosthesis 100 such that degradation of degradable fixation wire 120 breaks the connection to non-degradable fixation wire 140, which is beneficial to prevent non-degradable fixation wire 140 from entering the leaflets and causing the leaflets to fail. It should be noted that the degradable fixing thread 120 shown in fig. 7 is linear, and in other embodiments, the shape of the degradable fixing thread 120 is not limited as long as it can be connected to the heart valve prosthesis 100 and the non-degradable fixing thread 140 and can be any shape that can be degraded.

The implantable device described above is further illustrated by the specific embodiments below.

Example 1

A heart valve prosthesis comprises an instrument body and a degradable fixing line, wherein the fixed end of the degradable fixing line is fixedly connected with the instrument body, and the free end of the degradable fixing line is suspended.

The degradable fixed wire comprises a fixed wire body and a degradation-delaying coating covering the surface of the fixed wire body. The fixing wire body is in a slender cylindrical shape, the diameter of the bottom surface of the cylinder is 0.2mm, the fixing wire body is made of racemic polylactic acid, the weight-average molecular weight of the racemic polylactic acid is 10000Da, the polydispersity is 1.2, and the crystallinity is 35%. The material of the degradation-delaying coating is polycaprolactone, the weight-average molecular weight of the polycaprolactone is 10000Da, and the polydispersity is 1.1. The thickness of the degradation-retarding coating gradually increases from the fixed end to the free end along the length direction of the fixing line body. The minimum thickness of the degradation delaying coating is 0mm, the maximum thickness of the degradation delaying coating is 0.2mm, the thickness of the degradation delaying coating is linearly increased from the fixed end to the free end along the direction of the fixed line body, and the amplification is 1 mm/m.

The initial length of the degradable immobilization line was measured, and then the degradable immobilization line was immersed in PBS buffer at 37 ℃, no significant debris was observed after one year, and the length of the degradable immobilization line was measured to be 15% shorter than the initial length.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the thicker end of the degradation-delaying coating of the degradable fixed threads is respectively ligated with the femoral artery. Before implantation, the length of each degradable fixed line is 70mm (measured in a stretching state), nine months after implantation, the degradable fixed line in a rabbit is taken out, the phenomenon that the thicker end of the delayed degradation coating is not fractured is observed, and the length of the degradable fixed line is 50 mm. Eleven months after the implantation, the degradable fixing line in another rabbit is taken out, the thicker end of the degradation-delaying coating is still not broken, and the length of the degradable fixing line is 10 mm.

Example 2

The degradable fixed wire comprises a fixed wire body and a degradation-delaying coating covering the surface of the fixed wire body. The fixed wire body is in a shape of a long and thin circular truncated cone, the diameter of the upper bottom surface is 0.4mm, the diameter of the lower bottom surface is 0.7mm, and the wire diameter (cross-sectional diameter) of the fixed wire body 121 is linearly increased by 1mm/m along the length direction of the fixed wire body 121. The material of the fixing thread body is polylactic acid-glycolic acid copolymer (the molar ratio of lactic acid to glycolic acid is 50/50), the weight average molecular weight of the polylactic acid-glycolic acid copolymer is 10000Da, the polydispersity is 1.2, and the crystallinity is 50%. The material of the degradation-delaying coating is racemic polylactic acid, the weight-average molecular weight of the racemic polylactic acid is 5000Da, and the polydispersity is 1.5. The thickness of the degradation-retarding coating increases nonlinearly along the length direction of the fixing wire body from the fixed end to the free end. Wherein the minimum thickness of the degradation-delaying coating is 0.1mm, the maximum thickness of the degradation-delaying coating is 0.3mm, the coating thickness increases nonlinearly from the upper bottom surface to the lower bottom surface of the fixing line body, and the increase rule is a L²+0.1, where a-22 x 10^-5mm^-1L is the distance from the current cross section to the bottom surface, a L²The value of +0.1 is the diameter of the current section.

The initial length of the degradable securing line was measured and then the degradable securing line was immersed in a PBS solution at 37 c, and after one year, no significant fragments were observed, and the length of the degradable securing line was measured to be reduced by 5% from the initial length.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the thicker end of the degradation-delaying coating of the degradable fixed threads is respectively ligated with the femoral artery. Before implantation, the length of each degradable fixed line is 30mm (measured in a stretching state), nine months after implantation, the degradable fixed line in a rabbit is taken out, the phenomenon that the thicker end of the delayed degradation coating is not fractured is observed, and the length of the degradable fixed line is 28 mm. Eleven months after the implantation, the degradable fixing line in another rabbit is taken out, the thicker end of the degradation-delaying coating is still not broken, and the length of the degradable fixing line is 25 mm.

Example 3

The heart plugging device comprises a plugging device body and a degradable fixing line, wherein the fixed end of the degradable fixing line is fixedly connected with the plugging device body, and the free end of the degradable fixing line is suspended.

The degradable fixing wire has shape memory characteristic, and is in a mosquito-repellent incense-shaped structure in a natural state. The material capable of degrading the fixed line is polycaprolactone, a copolymer of diisocyanate and glycol, the ratio of the sum of the molar weight of the diisocyanate and the molar weight of the glycol to the molar weight of the polycaprolactone is 6:1, and the molar ratio of the diisocyanate to the glycol is 3: 2. The weight average molecular weight of the copolymer of polycaprolactone, diisocyanate and ethylene glycol was 10000Da, the polydispersity was 1.2 and the crystallinity was 35%. The degradable fixing line is in a shape of a slender round table, the diameter of the upper bottom surface of the fixing line is 0.1mm, the diameter of the lower bottom surface of the fixing line is 0.3mm, the diameter of the fixing line is linearly increased from the upper bottom surface to the lower bottom surface, and the amplification is 1.33 mm/m. Wherein, the one end that the lower bottom surface place is the free end, and the one end that the lower bottom surface place is the inside of mosquito-repellent incense column structure.

The initial length of the degradable fixing line was measured, and then the degradable fixing line was immersed in a PBS solution at 37 ℃, after one year, no significant fragments were observed, and the length of the degradable fixing line was measured, which was 20% shorter than the initial length.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the big ends of the degradable fixed threads are respectively ligated with femoral artery. Before implanting, the length of every degradable fixed line is 15mm (measure under the tensile state), implants nine months after, takes out the degradable fixed line in the rabbit, observes the big end of degradable fixed line and does not take place the fracture phenomenon, and degradable fixed line length is 10 mm. Eleven months after the implantation, the degradable fixing line in the other rabbit is taken out, the big end of the degradable fixing line is not broken, and the length of the degradable fixing line is 7 mm.

Example 4

The degradable fixed line has shape memory characteristic, and in natural state, the degradable fixed line is the heliciform, and the height of degradable fixed line is 3 mm. The degradable fixing line is made of a composite material of levorotatory polylactic acid and chitosan, the mass percent of the chitosan is 15%, the weight-average molecular weight of the chitosan is 50KDa, and the weight-average molecular weight of the levorotatory polylactic acid is 100 KDa. The degradable fixed line is long and thin round platform shape, and the last bottom surface diameter of fixed line is 0.15mm, and lower bottom surface diameter is 0.25mm, and the diameter of degradable fixed line increases along last bottom surface to lower bottom surface linearity, and the amplification is 0.2 mm/m. Wherein, the one end that lower bottom surface place is the free end.

The initial length of the degradable fixing line was measured, and then the degradable fixing line was immersed in a PBS solution at 37 ℃, after one year, no significant fragments were observed, and the length of the degradable fixing line was measured, which was 30% shorter than the initial length.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the big ends of the degradable fixed threads are respectively ligated with femoral artery. Before implanting, the length of every degradable fixed line is 50mm (measure under the tensile state), implants nine months after, takes out the degradable fixed line in the rabbit, observes the big end of degradable fixed line and does not take place the fracture phenomenon, and degradable fixed line length is 25 mm. Eleven months after the implantation, the degradable fixing line in the other rabbit is taken out, the big end of the degradable fixing line is not broken, and the length of the degradable fixing line is 15 mm.

Example 5

The material of the degradable fixing line is polylactic acid, the weight-average molecular weight of the polylactic acid is 100KDa, the polydispersity is 1.2, and the crystallinity is 40%. The degradable fixed line is long and thin round platform structure, and the last bottom surface diameter of degradable fixed line is 0.05mm, and lower bottom surface diameter is 0.2mm, and the diameter of degradable fixed line increases along last bottom surface to lower bottom surface linearity, and the amplification is 0.375 mm/m.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the big ends of the degradable fixed threads are respectively ligated with femoral artery. Before implanting, the length of every degradable fixed line is 40mm (measure under the tensile state), implants nine months after, takes out the degradable fixed line in the rabbit, observes the big end of degradable fixed line and does not take place the fracture phenomenon, and degradable fixed line length is 20 mm. Eleven months after the implantation, the degradable fixing line in the other rabbit is taken out, the big end of the degradable fixing line is not broken, and the length of the degradable fixing line is 10 mm.

Example 6

The material of the degradable fixing line is polylactic acid, the weight-average molecular weight of the polylactic acid is 100KDa, the polydispersity is 1.2, and the crystallinity is 40%. The degradable fixing line is in a slender round table structure, the diameter of the upper bottom surface of the degradable fixing line is 0.05mm, the diameter of the lower bottom surface of the degradable fixing line is 0.32mm,and the diameter of the degradable fixed line increases nonlinearly from the upper bottom surface to the lower bottom surface according to the increasing rule of 1.000656^L0.9, L is the distance of the current cross section to the upper bottom surface. 1.000656^LThe value of-0.9 is the diameter of the current section.

The same two degradable fixed threads are respectively implanted into the blood vessels of two rabbits, and the big ends of the degradable fixed threads are respectively ligated with femoral artery. Before implanting, the length of every degradable fixed line is 40mm (measure under the tensile state), implants nine months after, takes out the degradable fixed line in the rabbit, observes the big end of degradable fixed line and does not take place the fracture phenomenon, and degradable fixed line length is 25 mm. Eleven months after the implantation, the degradable fixing line in the other rabbit is taken out, the big end of the degradable fixing line is not broken, and the length of the degradable fixing line is 15 mm.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims

1. An implantable device, including the apparatus body, its characterized in that still includes the fixed line of degradable, the fixed line of degradable includes the fixed line body, the fixed line body has stiff end and free end, the stiff end with apparatus body fixed connection, the free end is used for fixing to the tissue on, the degradation of fixed line body is followed the stiff end extremely the free end is followed the length direction of fixed line body degrades gradually to realize through one of following two kinds of modes:

from the fixed end to the free end, along the length direction of the fixed wire body, the wire diameter of the fixed wire body is gradually increased or gradually decreased, so that the degradation of the fixed wire body is gradually degraded from the fixed end to the free end along the length direction of the fixed wire body;

or, the fixed line of degradable still includes the cladding the regulation and control degradation coating on fixed line body surface, regulation and control degradation coating is for delaying the degradation coating, the degradation that delays the degradation coating is followed the stiff end extremely the free end is followed the length direction of fixed line body degrades gradually, makes the degradation of fixed line body is followed the stiff end extremely the free end is followed the length direction of fixed line body degrades gradually.

2. The implantable device of claim 1, wherein the degradation retarding coating has a thickness that gradually increases along the length of the fixation wire body from the fixed end to the free end such that degradation of the fixation wire body gradually degrades along the length of the fixation wire body from the fixed end to the free end.

3. The implantable device of claim 1, wherein the regulatory degradation coating is a degradation promoting coating, wherein a degradation rate of the degradation promoting coating gradually decreases along a length direction of the fixation wire body from the fixed end to the free end, such that degradation of the fixation wire body gradually degrades along the length direction of the fixation wire body from the fixed end to the free end.

4. The implantable device of claim 1, wherein the degradation-retarding coating is made of at least one material selected from the group consisting of poly (lactic-co-glycolic acid), poly (racemic lactic acid), poly (caprolactone), poly (l-lactic acid), and poly (urethane).

5. The implantable device of claim 1, wherein the fixation wire body has a shape memory property such that a length of the fixation wire body in a natural state is less than a length of the fixation wire body in an operational state.

6. The implantable device of claim 5, wherein the fixation wire body is, in a natural state, a spiral, a mosquito coil, or an irregular shape.

7. The implantable device of claim 5, wherein the height of the fixation wire body is less than 5 millimeters in a natural state.

8. The implantable device of claim 1, wherein the material of the fixation wire body is a polycaprolactone-based shape memory material, an levopolylactic acid-based shape memory material, a polyurethane-based shape memory material, a polylactic-co-glycolic acid-based shape memory material, or a poly-p-dioxanone-based shape memory material.

9. The implantable device of claim 8, wherein the wire diameter of the fixation wire body is 0.1-4.0 mm.

10. The implantable device of claim 1, further comprising a non-degradable fixation wire coupled to a free end of the degradable fixation wire.