Stent with controllable dissolution rate and preparation method thereof

Abstract

The invention belongs to the field of medical instruments, and particularly relates to a dissolution rate controllable stent and a preparation method thereof. The support base material is composed of PVA and starch, and the PVA hydroxyl content is 87%-93%; magnetic particles are uniformly dispersed in the base material, the specific absorption rate of the magnetic particles is 300-600W / g, the particle size of the magnetic particles is not higher than 25nm, and the content of the magnetic particles in the stent is not lower than 1wt%; the preparation method comprises the following steps: (a) uniformly mixing a PVA (Polyvinyl Alcohol) aqueous solution with a gelatinized starch aqueous solution to obtain a basic spinning solution; (b) adding PVA and magnetic particles into water, uniformly mixing to obtain a dispersion liquid, dropwise adding the dispersion liquid into the basic spinning solution, uniformly mixing, then adding a surfactant and a developer, and uniformly mixing to obtain a spinning solution; and (c) carrying out electrostatic spinning on the spinning solution, and sequentially carrying out heat treatment, washing and freeze drying to obtain the stent, the stent can be instantly and rapidly dissolved by means of an external magnetic field.

Description

Technical Field

[0001] The present invention belongs to the field of medical devices and relates to a stent with controllable dissolution rate and a preparation method thereof. Background Art

[0002] In the field of modern medicine, stents, as an important type of medical device, are widely used in the treatment of various diseases of lumen stenosis or obstruction. From the implantation of vascular stents for cardiovascular diseases to the application of ureteral stents in the urinary system, stents play a crucial role in restoring the normal function of the lumen and ensuring the health of patients. However, current stent technology still faces many challenges, especially in terms of dissolution performance, and there are obvious deficiencies in existing stents.

[0003] The dissolution rate of existing stents in the body is difficult to flexibly control. For example, in the literature (Investigation of the degradation behavior of poly-L-lactic acid braided stents under real-time and accelerated conditions, Polymer Testing, Volume 141, December 2024, 108632.), a poly-L-lactic acid (PLLA) braided stent was used, and through real-time (37°C) and accelerated (50°C) degradation experiments, the molecular weight changes, crystallinity, mechanical properties, and degradation behavior of the stent were systematically studied. The research shows that the degradation rate of the PLLA stent is pre-determined by its initial molecular weight and crystallinity. The molecular weight decreases linearly with time, and the stent fails due to brittle fracture at about 13 months. Although accelerated degradation can shorten the experimental period, the degradation rate still cannot be flexibly controlled, and the later degradation behavior deviates from the real physiological conditions. Such a stent can only dissolve at a fixed slow rate (about 12 - 18 months), which cannot match the blood vessel repair cycle (3 - 6 months), and lacks the ability to dynamically respond to the pathological environment (such as infection). This single dissolution mode cannot meet the diverse clinical needs. For example, during the treatment of certain diseases, the recovery speed of patients varies. Some patients may have their conditions effectively alleviated in a relatively short time. At this time, if the stent can dissolve quickly and be excreted from the body, it can reduce the potential risks brought by the long-term retention of the stent in the body, such as infection, inflammatory reaction, and irritation to surrounding tissues. However, the existing slow-dissolving stents cannot meet this requirement.

[0004] On the other hand, for some patients with relatively complex conditions and long recovery periods, the stent needs to continuously provide stable support for a long time. At this time, if the dissolution rate of the stent is too fast, the treatment effect cannot be guaranteed. However, it is difficult for the existing technology to flexibly slow down the dissolution of the stent according to the actual treatment situation. This current situation where the dissolution rate is uncontrollable greatly limits the clinical application effect of the stent and also increases the treatment risk and medical cost of patients.

[0005] In summary, the defects of the existing stent in terms of dissolution rate regulation urgently require new technologies and materials to be improved to meet the growing demand for precision medicine and enhance the treatment experience and rehabilitation effect of patients. Summary of the Invention

[0006] The purpose of the present invention is to solve the problems existing in the prior art and provide a stent with a controllable dissolution rate and a preparation method thereof.

[0007] To achieve the above object, the technical scheme adopted by the present invention is as follows:

[0008] A stent with a controllable dissolution rate, the base material is composed of PVA and starch, and the hydroxyl content of PVA is not higher than 93%. The hydroxyl content is the proportion of the number of hydrolyzed reaction and converted into vinyl alcohol structural units in every 100 PVA repeating units. If the hydroxyl content is too high, the stent will be difficult to dissolve due to too strong hydrogen bond interaction;

[0009] Magnetic particles are uniformly dispersed in the base material. The specific absorption rate of the magnetic particles is 300 - 600 W / g. Based on this specific absorption rate, the magnetic particles can generate heat in a weak magnetic field environment, and the generated heat will not be too high; the particle size of the magnetic particles is not higher than 25 nm. If the particle size is too large, it may damage the PVA continuous phase, causing greater loss and requiring a stronger magnetic field to play a role, thereby causing local overheating and tissue damage; the content of magnetic particles in the stent is not less than 1 wt%. If the content is too low, the effect will not be obvious.

[0010] As a preferred technical scheme:

[0011] For the stent with a controllable dissolution rate as described above, the mass ratio of PVA to starch is 1 - 3:20. This mass ratio range can effectively ensure that the stent has good mechanical strength and prevent the brittleness of the stent from increasing.

[0012] A stent with controllable dissolution rate as described above, the hydroxyl group content of PVA is not less than 87%, which can ensure excellent mechanical properties of the stent; the molecular weight of PVA is 85000 - 200000 Da, at this time the solubility of PVA is relatively moderate, and the spinning solution formed thereby is more uniform during the spinning process, and the molecular chain has appropriate stiffness, so that the finally obtained spun fiber still has a certain mechanical strength.

[0013] A stent with controllable dissolution rate as described above, the starch is hydroxypropyl starch, and this starch has good compatibility with PVA and better solubility.

[0014] A stent with controllable dissolution rate as described above, the content of magnetic particles in the stent is not higher than 3 wt%; the particle size of the magnetic particles is not less than 15 nm, so as to avoid the magnetic particles being captured by the mucosal layer during excretion and directly migrating outside the PVA after magnetic response; the magnetic particles are magnetite, γ-Fe 2 O 3 , cobalt ferrite, manganese ferrite or pure iron nanoparticles.

[0015] A stent with controllable dissolution rate as described above, a surfactant (such as Tween80) is also uniformly dispersed in the substrate to prevent agglomeration, and the content of the surfactant in the stent is 0.1 - 0.15 wt%.

[0016] A stent with controllable dissolution rate as described above, a developer (such as BaSO 4 ) is also uniformly dispersed in the substrate for subsequent X-ray positioning, and the content of the developer in the stent is 10 - 20 wt%.

[0017] A stent with controllable dissolution rate as described above, the mechanical properties of the undissolved stent are excellent. The compressive strength of the undissolved stent is 105.27 - 108.65 cN, the elastic recovery rate is 79.25 - 81.59%, the breaking strength is 70.15 - 80.23 N, and the elongation at break is 185.323 - 189.729%;

[0018] When no magnetic field is applied to the stent, the dissolution rate of the stent is slow. After soaking in PBS buffer solution at 37°C for 14 days, compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 10 - 15%, the reduction rate of the elastic recovery rate is 10 - 13%, the reduction rate of the breaking strength is 9.8 - 11.9%, and the reduction rate of the elongation at break is 10 - 15%;

[0019] When a magnetic field is applied to the stent, the dissolution rate of the stent is relatively fast. After soaking in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 42 - 44.5 °C. Compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 95.0 - 99.5%, the reduction rate of the elastic recovery rate is 95.0 - 99.0%, the reduction rate of the breaking strength is 94.5 - 98.0%, and the reduction rate of the elongation at break is 93.5 - 98.5%. The magnetic field strength is 0.6 T and the magnetic field frequency is 100 Hz;

[0020] When the stent is implanted into the body, in the initial stage of treatment, the stent can not only provide appropriate mechanical support, but also show good drainage effect due to the hydrophilic characteristics of the material, effectively meeting the short-term drainage needs after surgery;

[0021] When the service period of the stent in the body ends, for example, when the obstruction has been relieved or the stent is no longer needed, under normal circumstances, the PVA molecular chains will gradually absorb water and swell in body fluids (such as urine), resulting in the breakage of hydrogen bonds and the dissociation of molecular chains, and then dissolution. However, this process not only requires a relatively high temperature but also is slow; while in the present invention, by adding an external magnetic field, the magnetic particles in the stent will start to move violently under the action of the magnetic field, thus dispersing or breaking the PVA macromolecular chains and promoting their depolymerization; at the same time, the local heat generated by the external alternating magnetic field (AC magnetic field) can exactly provide a temperature of about 50 °C, which is exactly the dissolution temperature of PVA. This temperature accelerates the destruction of the PVA cross-linked network and promotes the breakage of hydrogen bonds through intramolecular swelling; in addition, the stent selects PVA macromolecular chains with a higher proportion of hydroxyl groups, which have good drainage effects due to their hydrophilicity, further promoting the water-soluble effect of the stent; the present invention realizes the instant and rapid dissolution of the stent by using an external magnetic field, enabling it to be smoothly discharged from the body.

[0022] The present invention also provides a method for preparing a stent with a controllable dissolution rate as described above, including the following steps:

[0023] (a) Mix a PVA aqueous solution (obtained by dissolving PVA in water at 80 - 90 °C and stirring until completely dissolved) with a gelatinized starch aqueous solution evenly to obtain a basic spinning solution;

[0024] (b) Add PVA and magnetic particles to water, mix evenly (the method is not limited, for example, ultrasonic treatment for 30 min), and after obtaining a dispersion liquid, drop the dispersion liquid into the basic spinning solution, mix evenly (the method is not limited, for example, magnetic stirring for 2 h), and then add a surfactant and a developer, and mix evenly to obtain a spinning solution;

[0025] In steps (a) to (b), PVA is added in two times. For the first time, PVA in the form of an aqueous solution is mixed evenly with the gelatinized starch aqueous solution, which is beneficial to the uniform mixing of the spinning solution; for the second time, PVA and magnetic particles are added to water and mixed evenly, aiming to let PVA uniformly coat the magnetic particles in advance;

[0026] (c) After electrospinning the spinning solution, heat treatment, washing, and freeze-drying are carried out in sequence to obtain the scaffold.

[0027] As a preferred technical solution:

[0028] In the method as described above, in step (a), the concentration of the PVA aqueous solution is 8 - 12 wt%; the concentration of the starch aqueous solution is 5 - 10 wt%, the temperature of the gelatinization treatment is 60 - 80 °C, and the time is 30 - 60 min. The purpose of controlling the conditions of the gelatinization treatment in this way is to prevent the starch granules from not rupturing, resulting in uneven spinning;

[0029] In step (c), the voltage of electrospinning is 12 - 15 kV, the receiving distance is 12 - 15 cm, and a rotating metal rod is selected as the receiver during electrospinning, so that a tubular scaffold can be formed; the temperature of the heat treatment is 80 - 100 °C, and the time is 1 - 2 h. The heat treatment can enhance the water resistance of the PVA and starch components, and washing can remove the unformed components.

[0030] Beneficial effects:

[0031] The scaffold with controllable dissolution rate of the present invention has excellent mechanical properties and drainage effects. Moreover, with the aid of an external magnetic field, the scaffold can achieve instant and rapid dissolution, improving the treatment experience and rehabilitation effect of patients. Specific embodiments

[0032] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0033] The following are the test methods for relevant performance indicators in each embodiment:

[0034] Hydroxyl content: According to the standard of GB / T 12010.3-2010, the sample is dried to constant weight at 105±2°C and ground through a 100-mesh sieve. Weigh 1.0 g (accuracy 0.0001 g) and dissolve it in 50 mL of deionized water. After heating to 90°C for dissolution and then cooling to 25°C, add 20 mL of 0.5 mol / L sulfuric acid aqueous solution (standardized by GB / T 601-2016) for hydrolysis for 2 h. Subsequently, titrate with 0.1 mol / L sodium hydroxide aqueous solution (same calibration) to the phenolphthalein end point (pH value 8.2 - 8.4), and calculate the degree of hydrolysis through the formula (degree of hydrolysis = (difference in consumption of sulfuric acid and sodium hydroxide × 44.05) / sample mass).

[0035] Specific Absorption Rate (SAR): According to IEC 62209-1:2016, use a vector network analyzer (such as Keysight N5222B, 10 MHz - 26.5 GHz) and a standardized SAM model. Fill the tissue-simulating fluid (conductivity 1.45±0.03 S / m, dielectric constant 40.0±2) at 25±1°C. Fix the sample to be measured on the side of the model ear and operate at the maximum emission power. Use an electric field probe (such as SPEAG EX3DV4) to scan the electric field strength with a resolution of ≤2 mm, and calculate the local specific absorption rate according to SAR = σ|E|² / ρ (σ is the conductivity, ρ = 1000 kg / m³).

[0036] Molecular weight: Determined by gel permeation chromatography (GPC) according to the standard of GB / T 36214-2018. Use a Waters 1515 chromatographic system, equipped with a TSKgel SuperMultipore HZ-M chromatographic column (column temperature controlled at 40±0.1°C) and a Waters 2414 differential refractive index detector (temperature set at 35±0.1°C). The mobile phase uses 0.1 mol / L NaNO 3 (For water-soluble samples, the flow rate is 1.0±0.05 mL / min). The standard sample is selected as narrow-distribution PEG or PS (whose molecular weight covers 50% - 150% of the expected value of the sample). The sample is dissolved into a concentration of 2.0±0.1 mg / mL (dissolved at 90±1°C for 2 h and then filtered through 0.22 μm). After the system is balanced for 60 minutes (requiring a baseline drift <5 nRIU / min), inject 20 μL of the standard sample to establish a calibration curve (R²≥0.995), repeat the test on the sample 3 times, and then calculate the molecular weight; the test environment is: temperature 25±1°C, humidity ≤60%.

[0037] Compressive strength: Referring to the standard "YY / T 0872-2013 Test Methods for Ureteral Stents", a compressive specimen with a length of 50 mm is taken. Using the compression method with a fixed distance, the maximum compression distance is specified as half of the stent inner diameter. A pressure foot with a diameter of 4 mm is selected, and the stent platform is moved upward at a speed of 10 mm / min until the pressure foot compresses the stent to 50% of its inner diameter. Record the compressive strength value at this moment.

[0038] Elastic recovery rate: Take a compressive specimen with a length of 50 mm. Using the compression method with a fixed distance, the maximum compression distance is specified as half of the stent inner diameter. A pressure foot with a diameter of 4 mm is selected. Using the LLY-06D artificial biological pipeline compressor produced by Laizhou Electronic Instrument Co., Ltd., the stent platform is moved upward at a speed of 10 mm / min until the pressure foot compresses the stent to 50% of its inner diameter. Then, maintain this compressed state for 5 seconds. Affected by stress relaxation, the compressive strength of the stent will decrease. Then, the stent platform is moved downward at a rate of 10 mm / min until the pressure foot separates from the stent surface, pause for 5 seconds, and then let the stent platform rise again to make the pressure foot contact the stent surface. Repeat the above operation twice to complete one test.

[0039] Breaking strength, breaking elongation: Use a microcomputer-controlled electronic universal material testing machine to test the axial tensile properties of the stent. Referring to the tensile test method for polymer ureteral stents in YY / T 0872-2013, set the stent tensile test parameters as: the tensile rate is 200 mm / min, and the gauge distance is 50 mm. Test the breaking strength and breaking elongation of the stent.

[0040] Example 1

[0041] A preparation method of a stent with controllable dissolution rate, the specific steps are as follows:

[0042] (1) Preparation of raw materials;

[0043] PVA: The molecular weight is 85000 - 90000 Da, and the hydroxyl content is 87%;

[0044] PVA aqueous solution: The concentration is 8 wt%, and it is obtained by dissolving PVA in hot water (80 °C) and stirring until completely dissolved;

[0045] Starch aqueous solution after gelatinization treatment: The starch is hydroxypropyl starch (manufacturer: Henan Hengrui Starch Technology Co., Ltd., model: HS-702), the concentration of the starch aqueous solution is 5 wt%, the gelatinization treatment temperature is 60 °C, and the time is 30 min;

[0046] Magnetic particles: γ-Fe 2 O 3Nanoparticles with a specific absorption rate of 300 W / g and a particle size of 15 - 25 nm;

[0047] Water;

[0048] Surfactant: Tween 80, manufactured by Hong Kong Jisenbei International Trade Co., Ltd., product number JS0135;

[0049] Developer: BaSO 4 ;

[0050] (2) Prepare a scaffold with a controllable dissolution rate;

[0051] (2.1) Mix the PVA aqueous solution and the gelatinized starch aqueous solution evenly to obtain a basic spinning solution; among them, the mass ratio of PVA to starch is 0.6:20;

[0052] (2.2) Add PVA and magnetic particles to an appropriate amount of water, mix evenly, and after obtaining a dispersion liquid, drop the dispersion liquid into the basic spinning solution, mix evenly, and then add a surfactant and a developer, and mix evenly to obtain a spinning solution;

[0053] (2.3) After electrospinning the spinning solution (using a rotating metal rod as the receiver), perform heat treatment, washing, and freeze-drying in sequence to obtain a scaffold with a controllable dissolution rate; among them, the voltage of electrospinning is 12 kV, and the receiving distance is 12 cm; the temperature of heat treatment is 80 °C, and the time is 1 h.

[0054] The content of magnetic particles in the finally prepared scaffold with a controllable dissolution rate is 1 wt%, the content of the surfactant is 0.1 wt%, the content of the developer is 10 wt%, and the mass ratio of PVA (the total PVA added in steps (2.1) and (2.2)) to starch is 1:20;

[0055] The compressive strength of the undissolved scaffold is 105.27 cN, the elastic recovery rate is 79.25%, the breaking strength is 70.15 N, and the breaking elongation rate is 185.323%;

[0056] When no magnetic field is applied to the scaffold, after soaking in a PBS buffer solution (manufactured by Wuhan Saiweier Biotechnology Co., Ltd., product number G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 14.2%, the reduction rate of the elastic recovery rate is 11.9%, the reduction rate of the breaking strength is 9.9%, and the reduction rate of the breaking elongation rate is 14.3%;

[0057] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the scaffold and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 43 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 98.3%, the reduction rate of the elastic recovery rate is 97.4%, the reduction rate of the breaking strength is 96.2%, and the reduction rate of the elongation at break is 95.2%.

[0058] Comparative Example 1

[0059] A method for preparing a scaffold is basically the same as that in Example 1, except that: the content of magnetic particles in the scaffold is 0.4 wt%.

[0060] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the scaffold and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 39 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 5.30%, the reduction rate of the elastic recovery rate is 6.23%, the reduction rate of the breaking strength is 5.29%, and the reduction rate of the elongation at break is 7.36%.

[0061] Comparing Example 1 with Comparative Example 1, it can be seen that when the content of magnetic particles in the scaffold is too low, the scaffold is difficult to dissolve rapidly under the action of a magnetic field.

[0062] Comparative Example 2

[0063] A method for preparing a scaffold is basically the same as that in Example 1, except that: the magnetic particles are replaced with γ-Fe coated with Si 2 O 3 nanoparticles with a specific absorption rate less than 300 W / g.

[0064] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the scaffold and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 39.5 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 7.35%, the reduction rate of the elastic recovery rate is 7.37%, the reduction rate of the breaking strength is 8.43%, and the reduction rate of the elongation at break is 7.12%.

[0065] Comparing Example 1 with Comparative Example 2, it can be seen that when the specific absorption rate of the magnetic particles in the scaffold is too small, the response to the applied magnetic field is not sensitive, so the water dissolution rate does not increase significantly when an external magnetic field is applied.

[0066] Comparative Example 3

[0067] A preparation method of a scaffold is basically the same as that of Example 1, except that: the particle size of the magnetic particles in the scaffold is 28 - 32 nm.

[0068] The compressive strength of the undissolved scaffold is 82.32 cN, the elastic recovery rate is 50.76%, the breaking strength is 45.29 N, and the elongation at break is 124.23%;

[0069] When no magnetic field is applied to the scaffold, after soaking in PBS buffer solution (manufacturer: Wuhan Sevier Biotechnology Co., Ltd., product number: G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 16.3%, the reduction rate of the elastic recovery rate is 15.82%, the reduction rate of the breaking strength is 12.26%, and the reduction rate of the elongation at break is 15.86%;

[0070] When a magnetic field is applied to the scaffold (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz), after soaking in PBS buffer solution at 37 °C for 20 min, the temperature of the PBS buffer solution rises to 40 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 85.24%, the reduction rate of the elastic recovery rate is 80.47%, the reduction rate of the breaking strength is 84.97%, and the reduction rate of the elongation at break is 85.84%.

[0071] Comparing Example 1 with Comparative Example 3, it can be seen that when the particle size of the magnetic particles in the scaffold is too large, due to the too large magnetic particles in the scaffold, the electrospun fibers are discontinuous, resulting in a great reduction in mechanical properties when undissolved, thus unable to meet the mechanical strength required for the in - vivo scaffold. At the same time, when the particle size of the magnetic particles in the scaffold is too large, it may also damage the PVA continuous phase, causing greater loss, and it is difficult to play the role of promoting dissolution without increasing the magnetic field strength.

[0072] Example 2

[0073] A preparation method of a scaffold with controllable dissolution rate is as follows:

[0074] (1) Preparation of raw materials;

[0075] PVA: The molecular weight is 104500 - 200000 Da, and the hydroxyl content is 90%;

[0076] PVA aqueous solution: The concentration is 10 wt%, obtained by dissolving PVA in hot water (85 °C) and stirring until completely dissolved;

[0077] Starch aqueous solution after gelatinization treatment: The starch is hydroxypropyl starch (manufacturer: Henan Hengrui Starch Technology Co., Ltd., model: HS - 702), the concentration of the starch aqueous solution is 7.5 wt%, the gelatinization treatment temperature is 70 °C, and the time is 45 min;

[0078] Magnetic particles: Cobalt ferrite nanoparticles with a specific absorption rate of 450 W / g and a particle size of 15 - 25 nm;

[0079] Water;

[0080] Surfactant: Tween 80, manufactured by Hong Kong Jisenbei International Trade Co., Ltd., product number JS0135;

[0081] Developer: BaSO 4 ;

[0082] (2)Prepare a scaffold with a controllable dissolution rate;

[0083] (2.1)Mix the PVA aqueous solution and the gelatinized starch aqueous solution evenly to obtain a basic spinning solution; among them, the mass ratio of PVA to starch is 1.5:20;

[0084] (2.2)Add PVA and magnetic particles to an appropriate amount of water, mix evenly, and after obtaining a dispersion liquid, drop the dispersion liquid into the basic spinning solution, mix evenly, then add the surfactant and the developer, and mix evenly to obtain a spinning solution;

[0085] (2.3)After electrospinning the spinning solution (using a rotating metal rod as the receiver), perform heat treatment, washing, and freeze-drying in sequence to obtain a scaffold with a controllable dissolution rate; among them, the voltage of electrospinning is 12.5 kV, the receiving distance is 12.5 cm; the temperature of heat treatment is 100 °C, and the time is 1.5 h.

[0086] The content of magnetic particles in the finally prepared scaffold with a controllable dissolution rate is 2 wt%, the content of the surfactant is 0.125 wt%, the content of the developer is 15 wt%, and the mass ratio of PVA to starch is 2:20;

[0087] The compressive strength of the undissolved scaffold is 106.03 cN, the elastic recovery rate is 80.27%, the breaking strength is 75.45 N, and the breaking elongation is 187.638%;

[0088] When no magnetic field is applied to the scaffold and it is immersed in a PBS buffer solution (manufactured by Wuhan Saiweier Biotechnology Co., Ltd., product number G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 13%, the reduction rate of the elastic recovery rate is 11.2%, the reduction rate of the breaking strength is 10.02%, and the reduction rate of the breaking elongation is 12.5%;

[0089] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the stent and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 44.5 °C. Compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 96.2%, the reduction rate of the elastic recovery rate is 96.7%, the reduction rate of the breaking strength is 95.7%, and the reduction rate of the elongation at break is 94.6%.

[0090] Example 3

[0091] A method for preparing a stent with controllable dissolution rate, the specific steps are as follows:

[0092] (1) Preparation of raw materials;

[0093] PVA: The molecular weight is 100,000 - 124,000 Da, and the hydroxyl content is 93%;

[0094] PVA aqueous solution: The concentration is 12 wt%, and it is obtained by dissolving PVA in hot water (90 °C) and stirring until completely dissolved;

[0095] Starch aqueous solution after gelatinization treatment: The starch is hydroxypropyl starch (manufacturer: Henan Hengrui Starch Technology Co., Ltd., model: HS - 702), the concentration of the starch aqueous solution is 10 wt%, the temperature of the gelatinization treatment is 80 °C, and the time is 45 min;

[0096] Magnetic particles: Manganese ferrite nanoparticles, the specific absorption rate is 600 W / g, and the particle size is 15 - 25 nm;

[0097] Water;

[0098] Surfactant: Tween 80, manufacturer: Hong Kong Jisenbei International Trade Co., Ltd., product number: JS0135;

[0099] Developer: BaSO 4 ;

[0100] (2) Preparation of a stent with controllable dissolution rate;

[0101] (2.1) Mix the PVA aqueous solution and the starch aqueous solution after gelatinization treatment evenly to obtain a basic spinning solution; wherein, the mass ratio of PVA to starch is 2.4:20;

[0102] (2.2) Add PVA and magnetic particles to an appropriate amount of water, mix evenly, and after obtaining a dispersion liquid, add the dispersion liquid dropwise to the basic spinning solution, mix evenly, then add the surfactant and the developer, and mix evenly to obtain a spinning solution;

[0103] (2.3) After subjecting the spinning solution to electrospinning (using a rotating metal rod as the receiver), heat treatment, washing, and freeze-drying are carried out in sequence to obtain a scaffold with a controllable dissolution rate; among them, the voltage of electrospinning is 15 kV, and the receiving distance is 15 cm; the temperature of heat treatment is 90 °C, and the time is 2 h.

[0104] In the finally obtained scaffold with a controllable dissolution rate, the content of magnetic particles is 2 wt%, the content of surfactant is 0.15 wt%, the content of developer is 20 wt%, and the mass ratio of PVA to starch is 3:20;

[0105] The compressive strength of the undissolved scaffold is 106.98 cN, the elastic recovery rate is 81.01%, the breaking strength is 78.32 N, and the elongation at break is 188.357%;

[0106] When no magnetic field is applied to the scaffold, after soaking in PBS buffer (manufacturer: Wuhan Sevier Biotechnology Co., Ltd., product number: G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 10%, the reduction rate of the elastic recovery rate is 10.0%, the reduction rate of the breaking strength is 9.8%, and the reduction rate of the elongation at break is 10%;

[0107] When a magnetic field is applied to the scaffold (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz), after soaking in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 44.5 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 95%, the reduction rate of the elastic recovery rate is 95%, the reduction rate of the breaking strength is 94.5%, and the reduction rate of the elongation at break is 93.5%.

[0108] Comparative Example 4

[0109] A method for preparing a scaffold is basically the same as that in Example 1, except that: the magnetic particles are replaced with manganese ferrite nanoparticles coated with citric acid with a specific absorption rate greater than 600 W / g.

[0110] The compressive strength of the undissolved scaffold is 105.20 cN, the elastic recovery rate is 79.19%, the breaking strength is 70.15 N, and the elongation at break is 185.323%;

[0111] When no magnetic field is applied to the scaffold, after soaking in PBS buffer (manufacturer: Wuhan Sevier Biotechnology Co., Ltd., product number: G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold is 5.30%, the reduction rate of the elastic recovery rate is 6.23%, the reduction rate of the breaking strength is 5.29%, and the reduction rate of the elongation at break is 7.36%;

[0112] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the stent and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 55 °C. Compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 99.48%, the reduction rate of the elastic recovery rate is 98.90%, the reduction rate of the breaking strength is 99.21%, and the reduction rate of the elongation at break is 98.69%.

[0113] Comparing Example 1 with Comparative Example 4 shows that when the specific absorption rate of magnetic particles in the stent is too high, the local system heats up rapidly, and excessive heat generated by the magnetic field easily causes local tissue burns.

[0114] Comparative Example 5

[0115] A method for preparing a stent is basically the same as that in Example 1, except that the hydroxyl content of PVA is 96%.

[0116] The compressive strength of the undissolved stent is 110.69 cN, the elastic recovery rate is 82.35%, the breaking strength is 78.29 N, and the elongation at break is 193.27%;

[0117] When no magnetic field is applied to the stent and it is immersed in PBS buffer (manufacturer: Wuhan Sevier Biotechnology Co., Ltd., product number: G4202) at 37 °C for 14 days, compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 4.37%, the reduction rate of the elastic recovery rate is 5.38%, the reduction rate of the breaking strength is 4.27%, and the reduction rate of the elongation at break is 5.29%;

[0118] When a magnetic field (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz) is applied to the stent and it is immersed in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rises to 40.5 °C. Compared with the undissolved stent, the reduction rate of the compressive strength of the stent is 60.23%, the reduction rate of the elastic recovery rate is 59.49%, the reduction rate of the breaking strength is 62.97%, and the reduction rate of the elongation at break is 59.26%.

[0119] Comparing Example 1 with Comparative Example 5 shows that when the hydroxyl content of PVA is too high, it is difficult for the stent to dissolve rapidly under the action of a magnetic field.

[0120] Example 4

[0121] A method for preparing a stent with a controllable dissolution rate is as follows:

[0122] (1) Preparation of raw materials;

[0123] PVA: molecular weight is 100000 - 124000 Da, hydroxyl content is 90%;

[0124] PVA aqueous solution: with a concentration of 10 wt%, obtained by dissolving PVA in hot water (85 °C) and stirring until completely dissolved;

[0125] Starch aqueous solution after gelatinization treatment: the starch is hydroxypropyl starch (manufactured by Henan Hengrui Starch Technology Co., Ltd., model HS-702), the concentration of the starch aqueous solution is 7.5 wt%, the gelatinization treatment temperature is 70 °C, and the time is 60 min;

[0126] Magnetic particles: magnetite nanoparticles, with a specific absorption rate of 600 W / g and a particle size of 15 - 25 nm;

[0127] Water;

[0128] Surfactant: Tween 80, manufactured by Hong Kong Jisenbei International Trade Co., Ltd., product number JS0135;

[0129] Developer: BaSO 4 ;

[0130] (2) Prepare a scaffold with a controllable dissolution rate;

[0131] (2.1) Mix the PVA aqueous solution and the starch aqueous solution after gelatinization treatment evenly to obtain a basic spinning solution; among them, the mass ratio of PVA to starch is 1.6:20;

[0132] (2.2) Add PVA and magnetic particles to an appropriate amount of water, mix evenly, and after obtaining a dispersion liquid, drop the dispersion liquid into the basic spinning solution, mix evenly, then add the surfactant and the developer, and mix evenly to obtain a spinning solution;

[0133] (2.3) After electrospinning the spinning solution (using a rotating metal rod as the receiver), perform heat treatment, washing, and freeze-drying in sequence to obtain a scaffold with a controllable dissolution rate; among them, the voltage of electrospinning is 12.5 kV, the receiving distance is 12.5 cm; the temperature of heat treatment is 90 °C, and the time is 1.5 h.

[0134] The content of magnetic particles in the finally prepared scaffold with a controllable dissolution rate is 3 wt%, the content of the surfactant is 0.15 wt%, the content of the developer is 20 wt%, and the mass ratio of PVA to starch is 2:20;

[0135] The compressive strength of the undissolved scaffold is 108.65 cN, the elastic recovery rate is 81.59%, the breaking strength is 80.23 N, and the breaking elongation is 189.729%;

[0136] When no magnetic field was applied to the scaffold, after soaking in PBS buffer (manufactured by Wuhan Sevier Biotechnology Co., Ltd., catalog number G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold was 15%, the reduction rate of the elastic recovery rate was 13.0%, the reduction rate of the breaking strength was 11.9%, and the reduction rate of the elongation at break was 15%;

[0137] When a magnetic field was applied to the scaffold (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz), after soaking in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rose to 43.5 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold was 99.1%, the reduction rate of the elastic recovery rate was 98.2%, the reduction rate of the breaking strength was 97%, and the reduction rate of the elongation at break was 97.9%.

[0138] Example 5

[0139] A method for preparing a scaffold with controllable dissolution rate, which is only different from Example 4 in that: the magnetic particles are pure iron nanoparticles (specific absorption rate and particle size are the same as in Example 4).

[0140] The compressive strength of the undissolved scaffold was 108.65 cN, the elastic recovery rate was 81.59%, the breaking strength was 80.23 N, and the elongation at break was 189.729%;

[0141] When no magnetic field was applied to the scaffold, after soaking in PBS buffer (manufactured by Wuhan Sevier Biotechnology Co., Ltd., catalog number G4202) at 37 °C for 14 days, compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold was 15%, the reduction rate of the elastic recovery rate was 13.0%, the reduction rate of the breaking strength was 11.9%, and the reduction rate of the elongation at break was 15%;

[0142] When a magnetic field was applied to the scaffold (magnetic field strength: 0.6 T, magnetic field frequency: 100 Hz), after soaking in PBS buffer at 37 °C for 20 min, the temperature of the PBS buffer rose to 42 °C. Compared with the undissolved scaffold, the reduction rate of the compressive strength of the scaffold was 99.5%, the reduction rate of the elastic recovery rate was 99.0%, the reduction rate of the breaking strength was 98.0%, and the reduction rate of the elongation at break was 98.5%.

[0143] Under the application of a magnetic field, compared with iron oxide nanoparticles, although pure iron nanoparticles can provide a faster dissolution rate for the scaffold, their dissociation products may cause complications such as inflammation, and the biocompatibility is poor.

Claims

1. A stent with controllable dissolution rate, characterized in that: The substrate is composed of PVA and starch, and the hydroxyl content of PVA is not higher than 93%. The hydroxyl content is the proportion of the number of vinyl alcohol structural units that have undergone hydrolysis reaction and converted into each 100 PVA repeating units. Magnetic particles are uniformly dispersed in the substrate, the specific absorption rate of the magnetic particles is 300-600 W / g, the particle size of the magnetic particles is not higher than 25 nm, and the content of the magnetic particles in the bracket is not lower than 1wt%.

2. A stent with controllable dissolution rate according to claim 1, characterized in that: The hydroxyl content of PVA is not less than 87%; the mass ratio of PVA to starch is 1-3:

20.

3. A stent with controllable dissolution rate according to claim 1, characterized in that: The molecular weight of PVA is 85000-200000 Da.

4. A stent with controllable dissolution rate according to claim 1, characterized in that: The starch is hydroxypropyl starch.

5. The stent with controllable dissolution rate according to claim 1, characterized in that: The content of magnetic particles in the bracket is not higher than 3wt%; the particle size of the magnetic particles is not lower than 15nm; the magnetic particles are ferroferric oxide, γ-Fe2O3, cobalt ferrite, manganese ferrite or pure iron nanoparticles.

6. A stent with controllable dissolution rate according to claim 1, characterized in that: A surfactant is also uniformly dispersed in the substrate, and the content of the surfactant in the bracket is 0.1-0.15wt%.

7. The stent with controllable dissolution rate according to claim 1, characterized in that: The developer is also evenly dispersed in the substrate, and the content of the developer in the bracket is 10-20wt%.

8. A stent with controllable dissolution rate according to any one of claims 1 to 7, characterized in that: The compression strength of the undissolved scaffolds was 105.27-108.65 cN, the elastic recovery rate was 79.25-81.59%, the breaking strength was 70.15-80.23 N, and the breaking elongation was 185.323-189.729%; When no magnetic field was applied to the stent, after being immersed in PBS buffer at 37°C for 14 days, the reduction rate of the compression strength of the stent was 10-15%, the reduction rate of the elastic recovery rate was 10-13%, the reduction rate of the breaking strength was 9.8-11.9%, and the reduction rate of the breaking elongation was 10-15% relative to the undissolved stent; When a magnetic field is applied to the stent, after soaking in PBS buffer at 37°C for 20 minutes, the temperature of the PBS buffer rises to 42-44.5°C. Relative to the undissolved stent, the reduction rate of the compression strength of the stent is 95.0-99.5%, the reduction rate of the elastic recovery rate is 95.0-99.0%, the reduction rate of the breaking strength is 94.5-98.0%, and the reduction rate of the breaking elongation is 93.5-98.5%. The magnetic field intensity is 0.6T and the magnetic field frequency is 100Hz.

9. A method for preparing a stent with controllable dissolution rate according to any one of claims 1 to 8, characterized in that: The following steps are involved: (a) uniformly mixing the PVA aqueous solution and the starch aqueous solution subjected to gelatinization treatment to obtain a basic spinning solution; (b) adding PVA and magnetic particles into water and mixing them uniformly to obtain a dispersion, then dropping the dispersion into a base spinning solution and mixing them uniformly, and then adding a surfactant and a developer and mixing them uniformly to obtain a spinning solution; (c) After the spinning solution is subjected to electrospinning, it is heat treated, washed, and freeze-dried in sequence to obtain the scaffold.

10. The method according to claim 9, characterized in that In step (a), the concentration of the PVA aqueous solution is 8-12wt%; the concentration of the starch aqueous solution is 5-10wt%, and the gelatinization temperature is 60-80°C and the time is 30-60min; In step (c), the voltage of electrospinning is 12-15 kV, the receiving distance is 12-15 cm, and a rotating metal rod is used as a receiver during electrospinning; the temperature of heat treatment is 80-100° C., and the time is 1-2 h.