Degradable intelligent deformation vein filter

Abstract

The invention discloses a degradable intelligent deformation vein filter. The vein filter comprises an annular supporting structure, a first deformation structure and a second deformation structure, the supporting structure and the filter screen are both made of degradable materials; a degradable material for preparing the filter screen comprises a shape memory function material, the deformation temperature of the shape memory function material is higher than the temperature of a human body, and a sensitive material is added into the degradable material of the filter screen; at least one part of the filter screen is in a contraction state of inwards contracting from the supporting structure under the condition of being lower than the deformation temperature; after the filter screen is implanted into a human body, the sensitive material is excited by an external field to heat to reach a deformation temperature condition, and the filter screen deforms and unfolds to an annular surface where the supporting structure is located. The vein filter can be completely degraded, does not need to be taken out, can be attached to the blood vessel wall and gradually endothelialize after the filtering blocking function is completed, does not generate degradation fragments, does not generate partial displacement, has good biocompatibility, and can ensure that the blood vessel is smooth for a long time.

Description

Technical Field

[0001] The invention belongs to the field of implantable medical devices, and in particular relates to a degradable intelligent deformable venous filter. Background Art

[0002] Thrombosis in the deep veins of the lower extremities or the inferior vena cava may cause pulmonary embolism after thrombosis, which is the third most common acute cardiovascular syndrome after myocardial infarction and stroke worldwide, and its incidence is increasing every year. Currently, methods for preventing deep vein thrombosis in the inferior vena cava system include anticoagulation therapy, catheter-directed thrombolytic therapy, and inferior vena cava filter placement. However, some specific populations, such as pregnant women, breastfeeding patients, and patients with malignant tumors, cannot prevent deep vein thrombosis in the inferior vena cava system through anticoagulation therapy and catheter-directed thrombolytic therapy, so inferior vena cava filter placement is required.

[0003] Widely used venous filters include permanent filters, removable filters (temporary permanent dual-purpose filters) and temporary filters. Permanent venous filters are the earliest filter form that came out and are widely used in clinical practice. Permanent venous filters have a cone-shaped filter body with barbs attached, which can be fixed on the wall of the vena cava to prevent the filter from shifting. However, due to the long-term implantation of permanent venous filters in the body, complications such as inferior vena cava perforation, filter displacement, secondary thrombosis leading to inferior vena cava occlusion, and recurrence of inferior vena cava thrombosis may occur. Removable venous filters are designed with barbs to fix the filter on the venous wall, and a small hook on the top of the filter, which can be removed by a gooseneck catcher. Removable filters can be placed in the body for a long time as permanent filters, or removed as temporary filters. However, as temporary filters, the time window for placement in the body is short, generally up to 2 weeks. If the time is too long, the filter will adhere to the blood vessel wall and be difficult to remove. Temporary filters have no barbs or claws to damage the vein wall, and the filter can be placed for a longer period of time, generally up to 4 to 6 weeks. However, after implantation, it still needs to be removed, which poses a risk of filter displacement and the difficulty of adhesion to the vascular wall after endothelialization.

[0004] In order to solve the problem of difficulty in removing venous filters, degradable venous filters have become a new research method in recent years. Degradable venous filters are made of degradable metal materials or biodegradable materials. After being placed in the human body to complete their functions, they can gradually degrade and do not need to be removed. However, during the degradation process, degradable venous filters are prone to produce degradation fragments. The fragments stay in the blood vessels and induce the formation of new thrombi, posing a safety hazard. At the same time, as the stability of the venous filter gradually decreases during the degradation process, when the local degradation is severe, part of the filter is also prone to fall off and shift, posing a risk to patient safety. Summary of the invention

[0005] The present application aims to solve the problems existing in existing venous filters, such as the need for secondary surgery to remove them, the damage of the blood vessel wall by the fixing claws, and the easy generation of degradation fragments or displacement when using degradable venous filters. The present application further provides a degradable and intelligently deformable venous filter that does not need to be removed, has no degradation fragments, can achieve overall endothelial degradation through deformation, and has a controllable deformation time. The present application also provides a method for preparing the venous filter.

[0006] The technical solution adopted by this application to solve the above technical problems is: A degradable intelligent deformable venous filter comprises: a supporting structure, which is annular; a filter screen, wherein both the supporting structure and the filter screen are made of degradable materials; the degradable material used to prepare the filter screen comprises a shape memory functional material, the deformation temperature of the shape memory functional material is higher than the human body temperature, and a sensitive material is added to the degradable material of the filter screen; the filter screen is in a contracted state where it contracts inwardly from the supporting structure under conditions below the deformation temperature; after the venous filter is implanted in the human body to complete the filtering function, the sensitive material is stimulated to generate heat through an external field to reach the deformation temperature condition, and the filter screen is deformed and expanded to the annular surface where the supporting structure is located.

[0007] The deformation temperature range of the shape memory functional material is 37°C-65°C.

[0008] The deformation temperature range of the shape memory functional material is 42°C-43°C.

[0009] The support structure is elastic and suitable for radial compression.

[0010] The support structure is made of a material with shape memory function. The support structure is annular when implanted in a human body, and its radial dimension under a condition below the deformation temperature is smaller than that under the condition of being implanted in a human body.

[0011] The degradable material for preparing the filter screen comprises polylauryl glycol-based polymer.

[0012] The sensitive material is at least one of a magnetic field sensitive material and a light sensitive material.

[0013] The diameter of the support structure when implanted in a human body is 0.5-3 cm, and the length of the support structure and the filter as a whole along the axial direction is 0.5-7 cm.

[0014] The filter is composed of a plurality of blocking arms, the proximal ends of the blocking arms are connected to the supporting structure, and under conditions below the deformation temperature, a bend is formed at or near the proximal end, and the distal ends of the blocking arms converge into endpoints to form a conical filter.

[0015] A drug coating is coated on the surface of the filter screen.

[0016] The preparation method of the biodegradable intelligent deformable venous filter is as follows: (1) preparing a support structure by means of a 3D printer; (2) placing the support structure prepared in step (1) in advance in a mold that matches the outer contour of the support structure in the unfolded state and the filter, and using a composite sensitive material with a shape memory function as a raw material to complete the printing of the filter; (3) placing the mold in a vacuum environment, curing at 60-120° C., taking out the venous filter, squeezing the filter in a circumferential direction, so that the filter shrinks as a whole in the axial direction to form a conical contraction state, and then placing it at -10-20° C. to fix the shape.

[0017] The shape memory functional material is polylauryl glycol, and the preparation method of the composite sensitive material polylauryl glycol is as follows: adding sensitive material to the polylauryl glycol precursor, performing magnetic stirring at 60-120° C., so that the sensitive material is evenly dispersed in the polylauryl glycol precursor to obtain the composite sensitive material polylauryl glycol.

[0018] The advantages of the degradable and intelligently deformable venous filter of the present invention are: The degradable and intelligently deformable venous filter of the present invention comprises a degradable material for preparing the filter screen, which comprises a material having a shape memory function and is compounded with one or more of a magnetic field sensitive, current sensitive, sound wave sensitive or light sensitive material. By applying a stimulation field source in vitro, the venous filter in vivo can be controlled to deform and the morphology of the venous filter screen can be controlled. The present invention controls the degradation kinetics of the shape memory material and its composite material, so that the degradation time of the filter screen structure can be controlled.

[0019] After the venous filter of the present invention is implanted in the human body to complete the thrombus blocking function, a field is applied in vitro to stimulate the sensitive material in the filter to generate heat, so that the shape memory functional material reaches the transition temperature, the filter is deformed, and the filter structure that was originally in a contracted state unfolds the annular surface where the support structure is located. At this time, the filter, like the support structure, can fit with the blood vessel wall, thereby achieving the endothelialization of the venous filter as a whole and finally achieving degradation. The endothelialization of the venous filter as a whole also ensures that no fragments are generated during the degradation process of the filter, avoiding safety hazards, and effectively preventing the filter from falling off and shifting due to different degradation rates of each part, reducing the risks brought by the degradation process of the filter.

[0020] As a preferred embodiment, the surface of the filter structure of the present invention is coated with thrombus-dissolving drugs and filter endothelialization-promoting drugs, which can dissolve thrombi after intervention and promote the endothelialization process of the filter when the filter structure is attached to the blood vessel wall.

[0021] In order to make the technical solution of the degradable intelligent deformable venous filter described in the present invention more clearly understood, the present invention is further described below in conjunction with the accompanying drawings and specific implementation methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a schematic diagram of the structure of the degradable and intelligently deformable venous filter in the contracted state according to the present invention; Figure 2 It is a schematic structural diagram of the degradable and intelligently deformable venous filter of the present invention in an unfolded state; Wherein, the accompanying drawings are marked as follows: 1- Support structure; 2-filter; 21-proximal end of the blocking arm; 22-distal end of the blocking arm. DETAILED DESCRIPTION Example 1

[0023] This embodiment provides a biodegradable and intelligently deformable venous filter, the structure of which is as follows: Figure 1 As shown, in the expanded state Figure 2 As shown. The venous filter includes a support structure and a filter screen 2. The support structure 1 is an annular structure with a radius of 3 cm in its natural state. As shown in the figure, the support structure 1 is an annular structure formed by approximately elliptical grid units connected and arranged in the transverse and longitudinal directions, and the thickness of the wire body constituting the grid unit is 1 mm. The support structure 1 and the filter screen 2 are both made of degradable materials, wherein the support structure 1 is preferably made of polycaprolactone; the filter screen 2 is made of polydodecanoic acid glycerol, and a magnetic field sensitive material nano iron oxide is also added to the polydodecanoic acid glycerol to form a temperature and magnetic field sensitive shape memory material, and its deformation temperature is 42°C.

[0024] A portion of the filter screen 2 is in a contracted state contracted inwardly from the support structure 1 under a condition below the deformation temperature. Figure 1As shown. In this embodiment, the filter 2 extends outward from one side of the support structure 1. The filter 2 is composed of a plurality of blocking arms. The proximal end of the filter 2, i.e., the proximal end 21 of each blocking arm, is connected to the edge of the support structure 1. In the contracted state, the proximal end is bent, and the distal end of the filter, i.e., the distal end 22 of each blocking arm, extends in a direction away from the support structure 1, and finally extends to an end point to form a conical filter 2. In this embodiment, the diameter of each blocking arm is 3 mm. The support structure 1 in this embodiment is elastic. As a preferred embodiment, the support structure 1 can be in a compressed state when implanted in the human body. The annular support structure 1 is compressed radially inward. After implantation in the human body, the support structure 1 is expanded by a balloon expansion device, or the support structure 1 is expanded again to restore to a ring structure with a radius of 3 cm by relying on its own elasticity. When the support structure 1 is expanded, the filter 2 is a conical structure with a bottom radius of 3 cm and an axial length of 3 cm. Since the diameter of the support structure 1 after compression is smaller than the diameter when implanted in the human body, that is, less than 3 cm, it is convenient for surgical operation. As a preferred embodiment, the diameter of the support structure 1 when implanted in the human body is suitably 0.5-3 cm, and the overall axial length of the support structure 1 and the filter 2 is suitably 0.5-7 cm. After the venous filter described in this embodiment is implanted in the human body, the filter in the contracted state can filter and intercept blood clots. After the venous filter completes the filtering function, the nano-iron oxide is stimulated to heat up to the deformation temperature condition through an external magnetic field, and the filter is deformed and expanded to the annular surface where the support structure is located. Figure 2 shown.

[0025] In the venous filter of this embodiment, a drug layer is coated on the surface of the filter 2 structure. The drug layer is a PEG8000 (polyethylene glycol 8000) loaded paclitaxel coating. The paclitaxel concentration is 3 μg / mm 2 , the coating thickness is 150 microns.

[0026] The preparation method of the degradable and intelligently deformable venous filter in this embodiment is as follows: (1) First, use a 3D printer to prepare a support structure 1. The printing material is polycaprolactone and the printing filament diameter is 400 μm.

[0027] (2) The support structure 1 prepared in step (1) is pre-placed in a mold that matches the outer contours of the support structure 1 and the filter 2 in the unfolded state, and the filter 2 is printed using a 3D printer using polydodecanoic acid glycerol composite nano-iron oxide as a raw material.

[0028] The preparation method of the composite nano iron oxide polylauryl glyceride is as follows: Glycerol and dodecanedioic acid are mixed in a molar ratio of 1:1 to obtain a mixture; the mixture is heated to 90° C. under a nitrogen atmosphere, and reacted for 24 hours under a stirring condition of 150 rpm / min to obtain a reactant; the reactant is placed in a vacuum environment and stirred for 6 hours to eliminate bubbles, thereby obtaining a polydodecane dioic acid glyceride precursor.

[0029] Nano iron oxide particles are added to a polylauryl glyceride precursor, wherein the amount of the nano iron oxide particles added is 10wt% of the polylauryl glyceride precursor, and the nano iron oxide is a nanosphere with a diameter of 50-100nm. As an optional implementation, the amount of the nano iron oxide particles added is preferably 3-30wt% of the polylauryl glyceride precursor; at 90°C, magnetic stirring is performed at a speed of 150rpm / min for 5 minutes to uniformly disperse the nano iron oxide in the polylauryl glyceride precursor, thereby obtaining polylauryl glyceride composited with nano iron oxide.

[0030] (3) The mold is placed in a vacuum environment and cured at 60°C for 3 days. After the curing is completed, the venous filter body is taken out of the mold, placed in a tube mold, and the filter screen 2 is squeezed in the circumferential direction so that the whole body shrinks in the axial direction to form a conical contraction state, such as Figure 1 As shown, the venous filter body in the contracted state is then placed at 0°C for 5 minutes to complete the shape fixation.

[0031] The implantation and working process of the venous filter in this embodiment are as follows: (1) In the initial state, the venous filter is placed in the catheter, and the support structure 1 of the venous filter is in a compressed state under the restriction of the catheter. After the venous filter is delivered to the target position of the vena cava, the venous filter is pushed out. At this time, the support structure 1 expands and unfolds under the action of its own elastic force. The support structure 1 returns to a ring shape and fits the blood vessel wall to play a supporting role and prevent the venous filter from shifting. At this time, the filter screen 2 has not yet reached the deformation temperature and is still in a Figure 1 The contracted state shown is used to block thrombus.

[0032] (2) After 4 weeks of implantation, when no venous filter is needed to block thrombus, an alternating magnetic field is applied in vitro, with a frequency of 5-100KHZ and a magnetic field strength of 1-50kV / m, to stimulate the nano-iron oxide to generate heat and heat up, stimulating the polylauryldiol in the filter 2 to reach 42°C and deform, and the filter 2 structure is unfolded to the annular surface where the support structure 1 is located, as shown in FIG. Figure 2As shown, at this time, the filter 2 also adheres to the blood vessel wall, completes endothelialization and degradation. The temperature of the filter 2 in this embodiment can reach 42°C under field stimulation, and will not damage human tissues and cells at this temperature. At the same time, this embodiment adds nano-iron oxide, which has excellent biosafety and is widely used in the field of biomedical engineering. It is one of the inorganic nanomaterials currently approved by the state for clinical use. In this embodiment, nano-iron oxide particles are composited in the shape memory material, and the filter structure and thrombus blocking situation can be observed by X-rays. Example 2

[0033] The structure of the main body of the biodegradable intelligently deformable venous filter in this embodiment is the same as that in embodiment 1. Figure 1 and Figure 2 As shown. The venous filter includes a support structure 1 and a filter screen 2. The support structure 1 is an annular structure with a radius of 3 cm. As shown in the figure, the support structure 1 is an annular structure formed by approximately elliptical grid units connected and arranged in the transverse and longitudinal directions, and the thickness of the wire body constituting the grid unit is 2 mm. The support structure 1 and the filter screen 2 are both made of degradable materials, wherein the support structure 1 is made of left-handed polylactic acid; the filter screen 2 is made of polydodecane diglyceride, and a light-sensitive material graphene oxide is also added to the polydodecane diglyceride to form a temperature and infrared light-sensitive shape memory material, and its deformation temperature is 43°C.

[0034] The filter screen 2 extends outward from one side of the support structure 1. The filter screen 2 is composed of a plurality of blocking arms. The proximal end of the filter screen, i.e., the proximal end 21 of each blocking arm, is connected to the edge of the support structure 1. In the contracted state, the proximal end is bent, and the distal end of the filter screen, i.e., the distal end 22 of each blocking arm, extends in a direction away from the support structure 1 and finally extends to an end point to form a conical filter screen 2. Figure 1As shown, the diameter of each blocking arm in this embodiment is 2mm. The support structure 1 in this embodiment is elastic. As a preferred embodiment, the support structure 1 can be in a compressed state when implanted in the human body. The annular support structure 1 is compressed radially inward so that its radial dimension is smaller than the radial dimension under the condition of implantation in the human body, which is suitable for minimally invasive implantation. After implantation in the human body, the support structure 1 is expanded by a balloon dilatation device, or the support structure 1 can be expanded again into an annular structure with a radius of 3cm by relying on its own elasticity. When the support structure 1 is expanded, the filter 2 is a conical structure with a bottom radius of 3cm and an axial length of 4cm. After the venous filter in this embodiment is implanted in the human body, the filter in the contracted state can intercept blood clots. After the venous filter completes the filtering function, the graphene oxide is stimulated to heat up by an external infrared magnetic field to reach the deformation temperature condition, and the filter is deformed and expanded to the annular surface where the support structure is located, as shown in FIG. Figure 2 shown.

[0035] In this embodiment, a heparin-loaded tenecteplase coating is provided on the surface of the filter 2 structure, the tenecteplase concentration is 1%, and the coating thickness is 200 microns.

[0036] The preparation method of the degradable and intelligently deformable venous filter in this embodiment is as follows: (1) First, use a 3D printer to prepare a support structure 1. The printing material is left-handed polylactic acid, and the printing filament diameter is 800 μm.

[0037] (2) The support structure 1 prepared in step (1) is pre-placed in a mold that matches the outer contours of the support structure 1 and the filter 2 in the unfolded state, and the filter 2 is printed using a 3D printer using a polydodecanoic acid glycerol-carbon nanoparticle composite material as a raw material.

[0038] The preparation method of the polydodecane diglyceride-graphene oxide composite material is: Glycerol and dodecanedioic acid are mixed in a molar ratio of 1:1 to obtain a mixture; the mixture is heated to 120° C. under a nitrogen atmosphere, and reacted for 36 hours under a stirring condition of 150 rpm / min to obtain a reactant; the reactant is placed in a vacuum environment and stirred for 6 hours to eliminate bubbles, thereby obtaining a polydodecane dioic acid glyceride precursor; Powdered graphene oxide is added to the polydodecanoic acid glycerol precursor, and the added amount of the graphene oxide accounts for 20wt% of the polydodecanoic acid glycerol precursor. As an optional embodiment, the added amount of the graphene oxide is suitably 3-30wt% of the polydodecanoic acid glycerol precursor; after adding the graphene oxide, magnetic stirring is performed at 90°C and at a speed of 150rpm / min for 10 minutes to uniformly disperse the graphene oxide in the polydodecanoic acid glycerol precursor to obtain a polydodecanoic acid glycerol-graphene oxide composite material.

[0039] (3) The mold is placed in a vacuum environment and cured at 90°C for 3 days. After the curing is completed, the venous filter body is taken out of the mold, placed in a tube mold, and the filter screen 2 is squeezed in the circumferential direction so that the whole body shrinks in the axial direction to form a conical contraction state, such as Figure 2 As shown, the venous filter body in the contracted state is then placed at 0°C for 5 minutes to complete the shape fixation.

[0040] The implantation and working process of the venous filter in this embodiment are as follows: (1) In the initial state, the venous filter is placed in the catheter, and the support structure 1 of the venous filter is in a compressed state under the restriction of the catheter. After the venous filter is delivered to the target position of the vena cava, the venous filter is pushed out, and at this time, the support structure 1 expands and unfolds under the action of its own elastic force, and the support structure 1 returns to a ring shape, fits the blood vessel wall, plays a supporting role, and prevents the venous filter from shifting. At this time, the filter screen 2 has not yet reached the deformation temperature and is still in a contracted state, which is used to block thrombus.

[0041] (2) After 4 weeks of implantation, when no venous filter is needed to block thrombus, near-infrared light is applied in vitro, with a power density range of 0.01-1 W / cm 2 , so that the venous filter is in a near-infrared field, stimulating graphene oxide to generate heat and heat up, so that the polydodecanoic acid glycerol in the filter 2 reaches 43°C and deforms, and the filter 2 structure unfolds to the annular surface where the support structure 1 is located. At this time, the filter 2 also adheres to the blood vessel wall, completes endothelialization and degradation. The temperature of the filter 2 in this embodiment can reach 43°C under field stimulation, and this temperature will not cause damage to human tissues and cells. The graphene oxide added in this embodiment has good biocompatibility and can ensure biological safety after implantation into the human body.

[0042] As an optional embodiment, the support structure 1 in the above embodiment can also be made of a shape memory material, such as polyurethane, epoxy polymer and other shape memory materials. In this case, the deformation temperature of the support structure 1 is lower than the human body temperature but higher than the room temperature. At room temperature, the support structure 1 is a shrinkage structure that shrinks radially inward, and its radial size becomes smaller, which is convenient for implantation. When implanted in the human body, the support structure 1 is deformed and expands into a ring shape.

[0043] In the above embodiments, the degradation kinetics of the shape memory material and its composite material are controlled so that the degradation time of the filter structure can be controlled. Specifically, by adjusting the synthesis process of the shape memory material and the addition ratio of the sensitive material, and conducting cell co-culture experiments, enzyme solution degradation tests and stress tests, the degradation kinetics curves of the composite material under biological factors, chemical factors and mechanical factors are detected, and combined with the in vivo subcutaneous / vascular wall degradation kinetics curves, the degradation kinetics of the composite material can be regulated.

[0044] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for those of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the claims.

Claims

1. A degradable intelligent deformable venous filter, characterized in that: include: A supporting structure, wherein the supporting structure is annular; The filter screen, the support structure and the filter screen are both made of degradable materials; The degradable material used to prepare the filter screen includes a shape memory material, the deformation temperature of the shape memory material is higher than the human body temperature, and a sensitive material is added to the degradable material of the filter screen; The filter screen is in a contracted state where the support structure contracts inwardly under a condition lower than the deformation temperature; After the venous filter is implanted in the human body to complete the filtering function, the sensitive material is stimulated to generate heat to reach the deformation temperature condition through the external field, and the filter is deformed and expanded to the annular surface where the support structure is located.

2. The degradable intelligent deformable venous filter according to claim 1, characterized in that: The deformation temperature range of the shape memory functional material is 37°C-65°C.

3. The degradable intelligent deformable venous filter according to claim 1, characterized in that: The deformation temperature range of the shape memory functional material is 42°C-43°C.

4. The degradable intelligent deformable venous filter according to claim 1, 2 or 3, characterized in that: The support structure is elastic and suitable for radial compression.

5. The degradable and intelligently deformable venous filter according to claim 1, 2 or 3, characterized in that: The support structure is made of a material with shape memory function. The support structure is annular when implanted in a human body, and its radial dimension under a condition below the deformation temperature is smaller than that under the condition of being implanted in a human body.

6. The degradable and intelligently deformable venous filter according to any one of claims 1 to 5, characterized in that: The degradable material for preparing the filter screen comprises polylauryl glycol-based polymer.

7. The degradable and intelligently deformable venous filter according to any one of claims 1 to 6, characterized in that: The sensitive material is at least one of a magnetic field sensitive material and a light sensitive material.

8. The degradable and intelligently deformable venous filter according to any one of claims 1 to 7, characterized in that: The diameter of the support structure when implanted in a human body is 0.5-3 cm, and the length of the support structure and the filter as a whole along the axial direction is 0.5-7 cm.

9. The degradable and intelligently deformable venous filter according to any one of claims 1 to 8, characterized in that: The filter is composed of a plurality of blocking arms, the proximal ends of the blocking arms are connected to the supporting structure, and under conditions below the deformation temperature, a bend is formed at or near the proximal end, and the distal ends of the blocking arms converge into endpoints to form a conical filter.

10. The degradable and intelligently deformable venous filter according to any one of claims 1 to 9, characterized in that: A drug coating is coated on the surface of the filter screen.

Images