Degradable smart morphing venous filter

Abstract

The application discloses a degradable intelligent variable shape vein filter, which comprises a ring-shaped support structure and a filter screen, wherein the support structure and the filter screen are made of degradable materials; the degradable material for preparing the filter screen comprises a shape memory functional material, the shape memory functional material has a deformation temperature higher than a human body temperature, and a sensitive material is added in the degradable material of the filter screen; at least a part of the filter screen is in a contracted state of being contracted inwardly from the support structure under a condition of being lower than the deformation temperature; after the filter screen is implanted into a human body, the sensitive material is excited to generate heat to reach the condition of the deformation temperature through an external field, and the filter screen is deformed and expanded to a ring surface where the support structure is located. The vein filter is completely degradable, does not need to be taken out, can be attached to a blood vessel wall and gradually endothelialized after a filtering function is completed, does not generate degradable fragments, does not have partial displacement, has good biocompatibility, and can ensure that the blood vessel is unobstructed for a long time.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of interventional medical devices, and particularly relates to a degradable intelligent deformable venous filter. BACKGROUND

[0002] Pulmonary embolism is the third most common acute cardiovascular syndrome in the world after myocardial infarction and stroke, and the incidence is increasing every year. At present, the methods for preventing deep venous thrombosis in the inferior vena cava system include anticoagulant therapy, catheter thrombolytic therapy and inferior vena cava filter placement. However, some specific groups of people, such as pregnant women, lactating patients and patients with malignant tumors, cannot prevent deep venous thrombosis in the inferior vena cava system through anticoagulant therapy and catheter thrombolytic therapy, and thus need to be treated by inferior vena cava filter placement.

[0003] The widely used venous filters include permanent filters, retrievable filters (temporary and permanent dual-purpose filters) and temporary filters. The permanent venous filter is the earliest filter form and is widely used in clinical practice. The permanent venous filter has a filter main body with a conical structure, and is attached with a barb to be fixed on the wall of the vena cava to prevent the filter from shifting. However, since the permanent venous filter is implanted in the body for a long time, it may cause complications such as perforation of the inferior vena cava, filter migration, secondary thrombosis leading to occlusion of the inferior vena cava and recurrence of inferior vena cava thrombosis. The retrievable venous filter has a barb to fix the filter on the vein wall, and at the same time has a small hook at the top of the filter, which can be taken out by a swan neck catcher. The retrievable filter can be used as a permanent filter and placed in the body for a long time, or used as a temporary filter and taken out. However, as a temporary filter, the time window for its placement in the body is relatively short, and the longest time is generally 2 weeks. If the time is too long, the filter will be integrated with the blood vessel wall and be difficult to take out. The temporary filter has no barb and no fixed claw to damage the vein wall. The filter can be placed for a longer time, and the longest time can reach 4-6 weeks. However, it still needs to be taken out after implantation, and there is a risk of filter migration. In addition, after endothelialization, the filter may be integrated with the blood vessel wall and be difficult to take out.

[0004] In order to solve the problem of difficulty in taking out the venous filter, in recent years, degradable venous filters have become a new research method. The degradable venous filter is made of degradable metal materials or biodegradable materials, and can gradually degrade after being placed in the human body to complete its function, without the need for taking out. However, during the degradation process of the degradable venous filter, degradation fragments are easily generated, which stay in the blood vessel and induce the formation of new thrombus, posing a safety hazard. At the same time, with the gradual reduction of the stability of the venous filter during the degradation process, when the local degradation is serious, part of the filter is also prone to fall off and shift, thereby posing a risk to the safety of the patient. SUMMARY

[0005] The application solves the problems of the existing venous filter, such as the need for secondary surgery for removal, damage to the blood vessel wall by the fixing claw, the generation of degradation fragments or displacement of the degradable venous filter, and further provides a degradable intelligent deformable venous filter which does not need to be removed, has no degradation fragments, can realize overall endothelial degradation through deformation, and the deformation time is controllable. The application also provides a preparation method of the venous filter.

[0006] The application solves the above technical problems by adopting the technical scheme of:

[0007] A degradable intelligent deformable venous filter, comprising: a support structure, the support structure being annular; a filter screen, the support structure and the filter screen being made of degradable materials; the degradable material for preparing the filter screen comprises a shape memory functional material, the shape memory functional material has a deformation temperature higher than the body temperature, and a sensitive material is added in the degradable material of the filter screen; the filter screen is in a contracted state of being contracted inward from the support structure under the condition of being lower than the deformation temperature; after the venous filter is implanted into the human body to complete the filtering function, the sensitive material is excited to heat to reach the condition of the deformation temperature by an external field, and the filter screen is deformed and expanded to the annular surface where the support structure is located.

[0008] The deformation temperature range of the shape memory functional material is 37-65 DEG C.

[0009] The deformation temperature range of the shape memory functional material is 42-43 DEG C.

[0010] The support structure has elasticity and is suitable for being compressed in the radial direction.

[0011] The support structure is made of a material having a shape memory function, the support structure is annular under the condition of being implanted into the human body, and the radial dimension of the support structure under the condition of being lower than the deformation temperature is smaller than the radial dimension under the condition of being implanted into the human body.

[0012] The degradable material for preparing the filter screen comprises a polydodecanedioic acid glyceride-based polymer.

[0013] The sensitive material is at least one of a magnetic field sensitive material and a light sensitive material.

[0014] The diameter of the support structure under the condition of being implanted into the human body is 0.5-3 cm, and the length of the support structure and the filter screen as a whole in the axial direction is 0.5-7 cm.

[0015] The filter screen is composed of a plurality of blocking arms, the proximal end of the blocking arm is connected with the support structure, a bend is formed at or close to the position of the proximal end under the condition of being lower than the deformation temperature, the distal end of the blocking arm converges into an end point to form a conical filter screen.

[0016] A drug coating is coated on the surface of the filter screen.

[0017] The preparation method of the degradable intelligent deformable vein filter is as follows: (1) a support structure is prepared by a 3D printer; (2) the support structure prepared in step (1) is placed in a mold in advance, the mold is consistent with the outer contour of the support structure and the filter screen in the expanded state, a shape memory functional material with a composite sensitive material is used as raw material, and printing of the filter screen is completed; (3) the mold is placed in a vacuum environment, and solidification is completed at 60-120 DEG C; the vein filter is taken out, the filter screen is extruded in the circumferential direction, the whole is contracted to form a conical contraction state in the axial direction, and then the vein filter is placed in a condition of-10-20 DEG C for setting.

[0018] The shape memory functional material is polyglycerol dodecanedioate, and the preparation method of the polyglycerol dodecanedioate of the composite sensitive material is as follows: a sensitive material is added in a polyglycerol dodecanedioate precursor, and magnetic stirring is carried out at 60-120 DEG C, so that the sensitive material is uniformly dispersed in the polyglycerol dodecanedioate precursor, and the polyglycerol dodecanedioate of the composite sensitive material is obtained.

[0019] The degradable intelligent deformable vein filter has the following advantages:

[0020] The degradable intelligent deformable vein filter has the following advantages:

[0021] The degradable intelligent deformable vein filter has the following advantages:

[0022] As a preferred embodiment, the surface of the filter screen structure is coated with a thrombolytic drug and a filter endothelialization promoting drug, so that the thrombus can be dissolved after intervention, and the endothelialization process of the filter when the filter screen structure is attached to the blood vessel wall is promoted.

[0023] To make the technical solution of the biodegradable intelligent deformable vein filter of the present invention clearer, the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. Attached Figure Description

[0024] Figure 1 The diagram shown is a structural schematic of the biodegradable intelligent deformable vein filter of the present invention in its contracted state.

[0025] Figure 2 The diagram shown is a structural schematic of the degradable intelligent deformable vein filter of the present invention in its unfolded state.

[0026] The attached figures are labeled as follows:

[0027] 1-Supporting structure;

[0028] 2-Filter screen; 21-Proximal end of the barrier arm; 22-Distal end of the barrier arm. Detailed Implementation Example 1

[0029] This embodiment provides a biodegradable, intelligently deformable venous filter, the main body of which, in a contracted state, resembles... Figure 1 As shown, in the unfolded state... Figure 2 As shown in the figure, the vein filter includes a support structure and a filter screen 2. The support structure 1, in its natural state, is a ring-shaped structure with a radius of 3 cm. As shown, the support structure 1 is a ring-shaped structure formed by connecting approximately elliptical grid units along the horizontal and vertical directions, with the thickness of the lines constituting the grid units being 1 mm. Both the support structure 1 and the filter screen 2 are made of biodegradable materials. The support structure 1 is preferably made of polycaprolactone; the filter screen 2 is made of poly(dodecanoic acid glycerol), and magnetic field-sensitive material nano-iron oxide is added to the poly(dodecanoic acid glycerol) to form a temperature and magnetic field-sensitive shape memory material with a deformation temperature of 42°C.

[0030] A portion of the filter 2, under conditions below the deformation temperature, is in a contracted state, shrinking inward from the support structure 1, such as... Figure 1The filter screen 2 is extended outward from one side of the support structure 1, and is composed of a plurality of blocking arms. The proximal end of the filter screen 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. The distal end of the filter screen, i.e. the distal end 22 of each blocking arm, extends away from the support structure 1 and finally extends to an end point, forming a tapered filter screen 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 inward along its radial direction. After implantation in the human body, the support structure 1 is expanded by a balloon expansion device or relies on the elastic force of the support structure 1 itself to expand again to a radius of 3 cm. In the expanded state of the support structure 1, the filter screen 2 is in a tapered 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 under the implantation condition in the human body, i.e. smaller than 3 cm, it is convenient for surgical operation. As a preferred embodiment, the diameter of the support structure 1 under the implantation condition in the human body is preferably 0.5-3 cm, and the overall length of the support structure 1 and the filter screen 2 along the axial direction is preferably 0.5-7 cm. In this embodiment, the filter screen in the contracted state can filter and intercept thrombus after the venous filter is implanted in the human body. After the venous filter completes the filtering function, the nano-iron oxide is heated to the deformation temperature by an external magnetic field, and the filter screen deforms and expands to the annular surface of the support structure. Figure 2 As shown.

[0031] In this embodiment, the venous filter has a drug layer coated on the surface of the filter screen 2. The drug layer is a PEG8000 (polyethylene glycol 8000) loaded paclitaxel coating, and the concentration of paclitaxel is 3 μg / mm 2 , and the coating thickness is 150 microns.

[0032] The preparation method of the degradable intelligent deformable venous filter in this embodiment is as follows:

[0033] (1) First, use a 3D printer to prepare the support structure 1. The printing material is polycaprolactone, and the printing wire diameter is 400 microns.

[0034] (2) The support structure 1 prepared in step (1) is pre-placed in a mold that matches the outer contour of the support structure 1 and the filter screen 2 in the expanded state. Use a 3D printer to complete the printing of the filter screen 2 using polyglyceryl dodecanedioate composite nano-iron oxide as the raw material.

[0035] The preparation method of the polyglyceryl dodecanedioate composite nano-iron oxide is as follows:

[0036] Mixing glycerol and dodecanedioic acid in a molar ratio of 1:1 to obtain a mixture; heating the mixture to 90°C under a nitrogen atmosphere, and reacting for 24 h under stirring at 150 rpm / min to obtain a reactant; placing the reactant in a vacuum environment under continuous stirring for 6 h to eliminate bubbles to obtain a polyglycerol dodecanedioate precursor.

[0037] Adding nano-iron oxide particles to the polyglycerol dodecanedioate precursor, the amount of the nano-iron oxide particles added accounting for 10 wt% of the polyglycerol dodecanedioate precursor, the nano-iron oxide being nanospheres with a diameter of 50-100 nm, and as an alternative embodiment, the amount of the nano-iron oxide particles added being suitably 3-30 wt% of the polyglycerol dodecanedioate precursor; magnetically stirring at 150 rpm / min for 5 min at 90°C to make the nano-iron oxide uniformly dispersed in the polyglycerol dodecanedioate precursor to obtain a polyglycerol dodecanedioate composite nano-iron oxide.

[0038] (3) Placing the mold in a vacuum environment and curing at 60°C for 3 days. After completion of the curing, taking the venous filter body out of the mold and placing it in a tube mold to extrude the filter screen 2 in the circumferential direction, so that the whole of the filter screen 2 is contracted in the axial direction to form a tapered contraction state, as shown in Figure 1 , and then placing the venous filter body in the contraction state in a 0°C environment for 5 min to complete the fixing of the shape.

[0039] The implantation and working process of the venous filter in this embodiment is as follows:

[0040] (1) In the initial state, the venous filter is placed in a 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 which time the support structure 1 expands and develops under the action of its own elastic force, the support structure 1 returns to a ring shape and is attached to the blood vessel wall to play a supporting role and prevent the venous filter from shifting, at which time the filter screen 2 has not yet reached the deformation temperature and is still in the contraction state shown in Figure 1 , for blocking thrombus.

[0041] (2) After 4 weeks of implantation without the need for the venous filter to block thrombus, an alternating magnetic field is applied externally, the frequency of the magnetic field being 5-100 KHZ and the magnetic field strength being 1-50 kV / m, the nano-iron oxide generates heat to raise the temperature, and the polyglycerol dodecanedioate in the filter screen 2 is stimulated to reach 42°C to cause deformation, and the structure of the filter screen 2 is developed to the ring surface where the support structure 1 is located, as shown in Figure 2At this time, the filter screen 2 is also attached to the blood vessel wall, completes endothelialization and degrades. In this embodiment, the temperature of the filter screen 2 can reach 42°C under field stimulation, and at this temperature, the human body tissue and cells will not be damaged. At the same time, this embodiment adds nano iron oxide, which has excellent biological safety and is widely used in the field of biomedical engineering. It is one of the inorganic nanomaterials approved by the state for clinical use at present. In this embodiment, nano iron oxide particles are compounded in the shape memory material, and the filter structure and thrombus blocking situation can be observed by X-ray. Embodiment 2

[0042] The degradable intelligent deformable venous filter in this embodiment has the same structure as the main body of embodiment 1, as shown in Figure 1 and Figure 2 The venous filter includes a support structure 1 and a filter screen 2. The support structure 1 is in the form of a ring structure with a radius of 3 cm, as shown in the figure, and is formed by connecting and arranging the grid elements in the transverse and longitudinal directions. The wire thickness of the grid element is 2 mm. The support structure 1 and the filter screen 2 are made of degradable materials, wherein the support structure 1 is made of left-handed polylactic acid; the filter screen 2 is made of polydodecanedioic acid glyceride, and photosensitive material graphene oxide is also added to the polydodecanedioic acid glyceride to form a temperature and infrared light sensitive shape memory material, and the deformation temperature is 43°C.

[0043] The filter screen 2 extends outward from one side of the support structure 1, and 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 position is bent. The distal end of the filter screen, i.e. the distal end 22 of each blocking arm, extends away from the support structure 1 and finally extends to an end point to form a tapered filter screen 2, as shown in Figure 1The diameter of each blocking arm in the embodiment is 2 mm. The support structure 1 in the embodiment is elastic, and as a preferred embodiment, the support structure 1 can be in a compressed state when implanted in the human body, and the annular support structure 1 is compressed radially inward, so that its radial dimension is smaller than the radial dimension in the implanted state in the human body, and is suitable for minimally invasive implantation. After implantation in the human body, the support structure 1 is expanded by a balloon expansion device, or relies on the elasticity of the support structure 1 itself, so that the support structure 1 can be expanded again into an annular structure with a radius of 3 cm. In the expanded state of the support structure 1, the filter screen 2 is in a conical structure with a bottom surface radius of 3 cm and an axial length of 4 cm. In the embodiment, the filter screen in the contracted state can play a role in intercepting thrombus after the venous filter is implanted in the human body. After the venous filter completes the filtering function, the filter screen is deformed and expanded to the annular surface where the support structure is located, as shown in Figure 2

[0044] In the embodiment, the filter screen 2 has a heparin-loaded tenecteplase coating on the surface of the structure, and the tenecteplase concentration is 1%, and the coating thickness is 200 microns.

[0045] The preparation method of the degradable intelligent deformable venous filter in the embodiment is as follows:

[0046] (1) The support structure 1 is first prepared using a 3D printer, and the printing material is left-handed polylactic acid, and the printing wire diameter is 800 microns.

[0047] (2) The support structure 1 prepared in step (1) is placed in a mold in advance, and the outer contour of the support structure 1 and the filter screen 2 in the expanded state is matched, and a 3D printer is used to complete the printing of the filter screen 2 using polyglyceryl dodecanedioate-carbon nanoparticle composite material as the raw material.

[0048] The preparation method of the polyglyceryl dodecanedioate-graphene oxide composite material is as follows:

[0049] 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 the reaction is carried out under the condition of 150 rpm / min stirring for 36 h to obtain a reaction product; the reaction product is placed in a vacuum environment and continuously stirred for 6 h to eliminate bubbles to obtain a polyglyceryl dodecanedioate precursor;

[0050] ​The polyglyceryl dodecanedioate precursor is added with powdered graphene oxide, and the amount of the graphene oxide added is 20% by weight of the polyglyceryl dodecanedioate precursor. As an optional embodiment, the amount of the graphene oxide added is preferably 3-30% by weight of the polyglyceryl dodecanedioate precursor. After the graphene oxide is added, the graphene oxide is uniformly dispersed in the polyglyceryl dodecanedioate precursor by magnetic stirring at 90°C and a rotation speed of 150 rpm / min for 10 minutes to obtain a polyglyceryl dodecanedioate-graphene oxide composite material.

[0051] (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 and placed in a tube mold to extrude the filter screen 2 in the circumferential direction, so that the whole filter screen 2 is contracted in the axial direction to form a tapered contraction state, as shown in FIG. 4B. Then, the venous filter body in the contraction state is placed at 0°C for 5 minutes to complete the fixation of the shape. Figure 2

[0052] The implantation and working process of the venous filter in the embodiment is as follows:

[0053] (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 develops under the action of its own elastic force, and the support structure 1 returns to a ring shape and is attached to the blood vessel wall to play a supporting role and prevent the venous filter from moving. At this time, the filter screen 2 has not reached the deformation temperature and is still in a contracted state and is used to block thrombus.

[0054] (2) When the venous filter is not needed to block thrombus after being implanted for 4 weeks, near-infrared light is applied externally, and the power density of the infrared light ranges from 0.01 to 1 W / cm 2 , so that the venous filter is in the near-infrared field, the graphene oxide generates heat to raise the temperature, and the polyglyceryl dodecanedioate in the filter screen 2 reaches 43°C to deform, and the structure of the filter screen 2 is expanded to the ring surface where the support structure 1 is located. At this time, the filter screen 2 is also attached to the blood vessel wall, completes endothelialization, and degrades. In the embodiment, the temperature of the filter screen 2 can reach 43°C under the field stimulation, and the temperature will not cause damage to human tissues and cells. The added graphene oxide has good biocompatibility and can ensure the biological safety after being implanted into the human body.

[0055] ​As an alternative embodiment, the support structure 1 in the above embodiments can also be made of shape memory functional materials such as polyurethane, epoxy polymer and the like, in which case the shape deformation temperature of the support structure 1 is lower than the human body temperature but higher than the room temperature, and the support structure 1 is in a contracted structure that is contracted radially inward and has a smaller radial dimension at the room temperature, facilitating the implantation operation, and the support structure 1 is deformed to expand into a ring shape when implanted in the human body.

[0056] In the above embodiments, the degradation time of the filter screen structure is controllable by controlling the degradation kinetics of the shape memory material and the composite material thereof. Specifically, the degradation kinetics curve of the composite material under biological factors, chemical factors and mechanical factors is detected by adjusting the synthesis process of the shape memory material and the addition ratio of the sensitive material, and performing cell co-culture experiment, enzyme solution degradation experiment and stress test, and the degradation kinetics of the composite material is regulated in combination with the degradation kinetics curve in the subcutaneous tissue / in the blood vessel wall in vivo.

[0057] The above embodiments only express several embodiments of the present application, and the description is relatively specific and detailed, but it should not be understood as a limitation on the patent scope of the present application. It should be noted that for ordinary skilled persons in the art, several modifications and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the claims.

Claims

1. A degradable smart morphing venous filter, characterized in that, The application relates to a venous filter, which comprises the following parts: a support structure in the shape of a ring; a filter screen made of degradable material; the degradable material for preparing the filter screen contains shape memory functional material, the shape memory functional material has a deformation temperature higher than the human body temperature, and sensitive material is added in the degradable material of the filter screen; the filter screen is in a contracted state of being contracted inwardly by the support structure under the condition of being lower than the deformation temperature; after the venous filter is implanted into the human body to complete the filtering function, the sensitive material is heated to the deformation temperature by an external field, and the filter screen is deformed and expanded to the ring surface where the support structure is located; the filter screen is composed of a plurality of blocking arms, the proximal end of the blocking arm is connected with the support structure, a bend is formed at or near the position of the proximal end under the condition of being lower than the deformation temperature, and the distal end of the blocking arm converges into an end point to form a conical filter screen.

2. The degradable smart morphing venous filter of claim 1, wherein, The shape memory functional material has a deformation temperature range of 37-65 DEG C.

3. The degradable smart morphing venous filter of claim 1, wherein, The shape memory functional material has a deformation temperature range of 42-43 DEG C.

4. The degradable smart morphing venous filter of claim 1 or 2 or 3, wherein, The support structure has elasticity and is suitable for radial compression.

5. The degradable, smart morphing vena cava filter of claim 4, wherein, The support structure is made of material with shape memory function, the support structure is in the shape of a ring under the condition of being implanted into the human body, and the radial size of the support structure under the condition of being lower than the deformation temperature is smaller than the radial size under the condition of being implanted into the human body.

6. The degradable, smart morphing vena cava filter of claim 5, wherein, The degradable material for preparing the filter screen contains polydodecanedioic acid glyceride-based polymer.

7. The degradable, smart morphing vena cava filter of claim 6, wherein, The sensitive material is at least one of magnetic field sensitive material and light sensitive material.

8. The degradable, smart morphing vena cava filter of claim 7, wherein, The diameter of the support structure under the condition of being implanted into the human body is 0.5-3 cm, and the length of the support structure and the filter screen along the axial direction is 0.5-7 cm.

9. The degradable, smart morphing vena cava filter of claim 8, wherein, The surface of the filter screen is coated with a drug coating.

Images