Biodegradable stent, preparation method thereof and biodegradable stent system

Abstract

The invention discloses a biodegradable stent, a preparation method thereof and a biodegradable stent system. The biodegradable stent comprises a stent body and a degradable material wrapping the surface of the stent body, the degradable material is of a core-shell structure, a core layer in the core-shell structure is a degradable adhesive layer, a shell layer in the core-shell structure is a degradable polymer layer, and the degradable adhesive layer comprises cyanoacrylate. A degradable material on the surface of the biodegradable stent is of a core-shell structure, an adhesive of a core layer is gradually released, the situation that the adhesive is possibly released suddenly due to the fact that the surface of the adhesive is covered with a water-soluble layer can be avoided, and after the stent is implanted into a lesion area through a conveying system, the degradable shell layer dissolves and releases the adhesive of the core layer to be bonded with the inner wall of a blood vessel; the stent can be prevented from shifting, the vascular wall cannot be damaged, and complications such as interlayers are avoided.

Description

Technical Field

[0001] The present application relates to the field of medical device technology, and further to the field of biodegradable polymer stents, and specifically to a biodegradable stent and a preparation method thereof, and a biodegradable stent system. Background Art

[0002] In the field of interventional therapy, biodegradable stents have been widely used clinically in recent years due to their advantages of intervention without implantation, and their application scenarios have gradually expanded from early coronary intervention to peripheral intervention. When used in peripheral lower limb arteries, stents are subjected to more complex stress conditions such as stretching, compression, bending, and torsion than coronary arteries, which can easily lead to stent displacement and complications such as thrombosis or aneurysm. Stent displacement accounts for a very high proportion of adverse events of peripheral lower limb artery stents.

[0003] Currently, some methods for improving stents to prevent them from shifting have been reported, but all of them have some shortcomings, for example: ① It has been reported that a biodegradable adhesive is set between the wall of the target lumen and the degradable stent to reduce the occurrence of displacement of the degradable stent, but the stent and balloon structure designed by this method is very complex, the processing is difficult, and the release of the adhesive is difficult to control; ② It has been reported that a self-expanding coated stent has been developed, with a coating and degradable barbs designed on both sides of the stent to reduce the risk of displacement or being carried away by the blood flow during the release of the stent, but the degradable barbs of this method may be damaged during the stent crimping process, and there is a risk of puncture of the blood vessel wall, resulting in dissection; ③ It has been reported that an anti-migration spiral layer is added to the outer surface of the stent to prevent the stent from sliding relative to the esophageal arm, but this method significantly increases the wall thickness of the stent, and because the spiral layer cannot be crimped, this structure is not suitable for balloon-expandable stents.

[0004] Therefore, in order to prevent the stent from shifting, it is urgent to develop a new stent. Summary of the invention

[0005] Based on this, it is necessary to provide a biodegradable stent and a preparation method thereof and a biodegradable stent system.

[0006] A first aspect of the present application provides a biodegradable stent, comprising a stent body and a degradable material coated on the surface of the stent body, wherein the degradable material is a core-shell structure, wherein the core layer of the core-shell structure is a degradable adhesive layer, and the shell layer is a degradable polymer layer, and the degradable adhesive layer comprises cyanoacrylate.

[0007] In some embodiments, the degradable material coated on the surface of the stent body is selected from one or more of degradable adhesive microspheres and degradable fiber layers.

[0008] In some embodiments, the cyanoacrylate includes one or more of methyl cyanoacrylate, ethyl cyanoacrylate, propyl cyanoacrylate, butyl cyanoacrylate, pentyl cyanoacrylate, hexyl cyanoacrylate, heptyl cyanoacrylate, and octyl cyanoacrylate.

[0009] In some embodiments, the degradable adhesive layer comprises cyanoacrylate; the degradable polymer layer comprises a degradable polymer with a molecular weight of 5000Da to 500000Da; the degradable polymer is selected from at least one of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol, and / or the degradable polymer is selected from a plurality of copolymers of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol.

[0010] In some embodiments, the material of the stent body is a biodegradable material; the biodegradable material includes one or more of a synthetic material and a natural material.

[0011] In some specific embodiments, the synthetic material includes at least one of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol, and / or the synthetic material includes multiple copolymers of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol; the natural material includes at least one of collagen, silk fibroin, chitin, chitosan, hyaluronic acid and sodium alginate.

[0012] The second aspect of the present application provides a method for preparing the biodegradable stent described in the first aspect of the present application, comprising the following steps:

[0013] preparing a stent body;

[0014] The degradable material with a core-shell structure is deposited on the surface of the stent body.

[0015] In some embodiments, the step of preparing the stent body includes preparing the stent body by at least one of laser engraving, weaving and 3D printing.

[0016] In some embodiments, the core-shell structured degradable material is prepared from a degradable binder and a shell layer solution by at least one of electrostatic spraying and electrostatic spinning.

[0017] In some embodiments, the shell solution includes a degradable polymer and an organic solvent, and the organic solvent includes one or more of hexafluoroisopropanol, dichloromethane, chloroform, N,N-dimethylformamide, tetrahydrofuran, ethanol, acetic acid, acetone, n-propyl acetate and n-butyl acetate.

[0018] In some embodiments, the mass fraction of the degradable polymer in the shell solution is 0.5% to 15%.

[0019] In some embodiments, the parameters of the electrostatic spraying include: a voltage of 4 kV to 10 kV, a receiving distance of 10 cm to 14 cm, an ambient temperature of 20° C. to 30° C., and an ambient humidity of 20% to 40%.

[0020] In some embodiments, the electrospinning parameters include: voltage of 12 kV to 20 kV, receiving distance of 16 cm to 20 cm, ambient temperature of 20° C. to 30° C., and ambient humidity of 20% to 40%.

[0021] The third aspect of the present application provides a biodegradable stent system, which includes the biodegradable stent described in the first aspect of the present application or the biodegradable stent prepared by the method described in the second aspect of the present application and a medical dilatation tube; the medical dilatation tube includes a balloon dilatation catheter.

[0022] In some embodiments, the balloon dilatation catheter comprises a balloon and a catheter.

[0023] The fourth aspect of the present application provides a method for preparing the biodegradable stent system described in the third aspect of the present application, comprising using a crimping device to crimp the biodegradable stent onto a medical expansion tube.

[0024] The aforementioned biodegradable stent contains a degradable material with a core-shell structure. Since the adhesive is located in the core layer, the adhesive in the core layer is gradually released, which can avoid the sudden release of the adhesive that may be caused by the water-soluble layer covering the adhesive surface. After the stent is implanted in the lesion area using the delivery system, the degradable shell layer dissolves and releases the adhesive in the core layer to adhere to the inner wall of the blood vessel, which can prevent the stent from shifting and will not cause damage to the blood vessel wall, avoiding complications such as dissection. Furthermore, the adhesive in the core layer is gradually released, which can also reduce the occurrence of ectopic embolism caused by the adhesive freeing the target area. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the implementation methods and examples of the present application and to more completely understand the present application and its beneficial effects, the following is a brief introduction to the drawings required for use in the description of the implementation methods or examples. Obviously, the drawings described below are only some embodiments of the present application, and those skilled in the art can obtain other drawings based on these drawings without creative work.

[0026] Figure 1 This is a graph showing the release of butyl cyanoacrylate from a biodegradable stent prepared by different methods in one embodiment of the present application.

[0027] Figure 2 Schematic diagram of the structure of a biodegradable stent in one embodiment of the present application. DETAILED DESCRIPTION

[0028] In order to facilitate the understanding of the present application, the present application will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present application are given in the drawings. However, the present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present application more thorough and comprehensive.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0030] The terms "having", "containing", "including" and "comprising" used in this application are synonymous, which are inclusive or open-ended and do not exclude additional, uncited members or features. Members or features include materials or components, structures, elements, instruments, etc.; non-limiting examples of members or features include actions, conditions for the occurrence of actions, timing, states, etc.

[0031] In this application, the technical features or technical solutions described in an open language include closed technical features or technical solutions composed of the listed contents, and also include open technical features or technical solutions containing the listed contents.

[0032] In this application, when referring to the unit of a data range, if there is a unit only after the right endpoint, it means that the units of the left endpoint and the right endpoint are the same.

[0033] In this application, if there are multiple steps involved in the method flow, unless there is a clear different description in this document, there is no strict order restriction for the execution of these steps, and they can be executed in other orders than described. Moreover, any step can include multiple sub-steps or multiple stages, and these sub-steps or stages are not necessarily executed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be executed in turn, alternating or simultaneously with other steps or parts of sub-steps or stages of other steps.

[0034] In the present application, exemplary descriptions such as "in some implementation modes (or examples)" and "in one implementation mode (or example)" may include but are not limited to the following meanings: these solutions may be combined with other solutions in a suitable manner to form new technical solutions.

[0035] In the present application, the terms "first", "second", "third", "fourth", etc. in "the first aspect", "the second aspect", "the third aspect", "the fourth aspect", etc. are used only for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "first", "second", "third", "fourth", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0036] In the present application, when it comes to a numerical interval (i.e., a numerical range), unless otherwise specified, the distribution of the optional numerical values ​​in the numerical interval is considered to be continuous, and includes the two numerical endpoints (i.e., the minimum and maximum values) of the numerical interval, and each numerical value between the two numerical endpoints. Unless otherwise specified, when the numerical interval only refers to an integer in the numerical interval, it includes the two endpoint integers of the numerical range, and each integer between the two endpoints, which is equivalent to directly listing each integer. When multiple numerical ranges are provided to describe features or characteristics, these numerical ranges can be merged. In other words, unless otherwise specified, the numerical range disclosed herein should be understood to include any and all sub-ranges included therein. The "numerical value" in the numerical interval can be any quantitative value, such as a number, a percentage, a ratio, etc. "Numerical interval" allows broadly including numerical interval types such as percentage intervals, ratio intervals, and ratio intervals.

[0037] At present, when biodegradable stents are used in peripheral lower limb arteries, the stents are subjected to more complex stress conditions such as stretching, compression, bending, and torsion compared to coronary arteries, which can easily lead to stent displacement and complications such as thrombosis or aneurysm. Stent displacement accounts for a very high proportion of adverse events in peripheral lower limb artery stents.

[0038] There are reports that a polymer stent with a soluble or degradable adhesive is invented. When exposed to an aqueous environment, the adhesive is activated to bond the stent and the blood vessel wall. However, this method has the problem that a large amount of adhesive in the coating is suddenly released during the adhesive release process, which may cause ectopic embolism.

[0039] A report pointed out that a biodegradable stent is used in which a biodegradable adhesive is set between the wall of the target lumen and the biodegradable stent to reduce the occurrence of displacement of the biodegradable stent. However, this method has the problems that the designed stent and balloon structure are very complex, the processing is difficult, and the release of the adhesive is difficult to control.

[0040] A report pointed out a self-expanding covered stent with a coating and degradable barbs on both sides of the stent to reduce the risk of the stent shifting or being carried away by the blood flow during release. However, this method has the problem that the degradable barbs may be damaged during the stent crimping process, and there is a risk of puncture of the blood vessel wall, leading to dissection.

[0041] A report pointed out a biodegradable esophageal stent with an anti-migration spiral structure, which prevents the relative sliding of the stent and the esophageal arm by adding an anti-migration spiral layer on the outer surface of the stent. However, this method significantly increases the wall thickness of the stent, and because the spiral layer cannot be compressed and gripped, this structure is not suitable for balloon-expandable stents.

[0042] Based on this, the embodiments of the present application at least provide a biodegradable stent and a preparation method thereof, and a biodegradable stent system.

[0043] In a first aspect of the present application, a biodegradable stent is provided, referring to Figure 2 , including a stent body and a degradable material coated on the surface of the stent body, wherein the degradable material is a core-shell structure, in which the core layer is a degradable adhesive layer and the shell layer is a degradable polymer layer.

[0044] In the present application, unless otherwise specified, "degradable adhesive layer" refers to the degradable adhesive being released from the degradable adhesive layer into a liquid environment.

[0045] In some embodiments, the degradable material coated on the surface of the stent body includes one or more of degradable adhesive microspheres and degradable fiber layers. It should be noted that the degradable adhesive microspheres and the degradable fiber layers are both core-shell structures, and the degradable adhesive microspheres and the degradable fiber layers can be replaced with each other on the surface of the stent body.

[0046] In some embodiments, the size of the core-shell structured degradable microspheres may be 1 µm to 50 µm.

[0047] In the present application, unless otherwise specified, the size of the core-shell structured degradable microspheres refers to the diameter of the core-shell structured degradable microspheres.

[0048] In some embodiments, the degradable adhesive layer contains a degradable adhesive, and the type of the degradable adhesive can be selected from conventional degradable adhesives in the art, such as but not limited to cyanoacrylate adhesives. Further, cyanoacrylate adhesives include but are not limited to methyl cyanoacrylate, ethyl cyanoacrylate, propyl cyanoacrylate, butyl cyanoacrylate, pentyl cyanoacrylate, hexyl cyanoacrylate, heptyl cyanoacrylate, octyl cyanoacrylate, and mixtures thereof.

[0049] In some embodiments, the degradable polymer layer includes a degradable polymer with a molecular weight of 5000Da to 500000Da. Further, the degradable polymer may be, but is not limited to, polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate, polyethylene glycol, and copolymers and mixtures thereof.

[0050] In some embodiments, the main material of the stent is a biodegradable polymer material, and the biodegradable polymer material includes synthetic polymer materials and natural polymer materials. Further, synthetic polymer materials include but are not limited to polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate, polyethylene glycol, and copolymers and mixtures of the above materials; natural polymer materials include but are not limited to collagen, silk fibroin, chitin, chitosan, hyaluronic acid, sodium alginate, etc.

[0051] In the present application, since the degradable material covering the surface of the stent body is a core-shell structure, the small molecule adhesive of the core layer is gradually released, and the small molecule adhesive is polymerized in situ in the blood environment to generate macromolecules, which can better adhere to the outer surface of the stent and the blood vessels, and better prevent the stent from shifting. Furthermore, the biodegradable stent can also avoid the sudden release of adhesive that may be caused by the water-soluble layer covering the adhesive surface, and can reduce the occurrence of ectopic embolism caused by the adhesive freeing the target area.

[0052] The second aspect of the present application provides a method for preparing the biodegradable stent of the first aspect of the present application, comprising the following steps:

[0053] S100: preparing the stent body;

[0054] S200: Depositing a degradable material with a core-shell structure on the surface of the stent body.

[0055] In some embodiments, the degradable material of the core-shell structure is prepared from the degradable binder and the shell layer solution by an electrostatic processing process.

[0056] In some embodiments, a method for preparing the degradable bioscaffold of the first aspect of the present application is provided, comprising the following steps:

[0057] S100': preparing the stent body;

[0058] S150': preparing degradable adhesive microspheres and / or degradable fiber layers from a degradable adhesive and a shell layer solution by an electrostatic processing process;

[0059] S200': depositing degradable adhesive microspheres and / or degradable fiber layers on the surface of the stent body.

[0060] In some embodiments, the stent body can be prepared by conventional technical means in the art, such as but not limited to laser engraving, weaving or 3D printing and other processing techniques.

[0061] In some embodiments, in step S150', the shell solution includes a degradable polymer and an organic solvent. Further, the types of organic solvents include but are not limited to hexafluoroisopropanol, dichloromethane, chloroform, N,N-dimethylformamide, tetrahydrofuran, ethanol, acetic acid, acetone, n-propyl acetate, n-butyl acetate and one or more of the mixtures of the above solvents.

[0062] In some embodiments, the mass fraction of the degradable polymer in the shell solution is 0.5% to 15%. Without limitation, the mass fraction of the degradable polymer in the shell solution can be, but is not limited to, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, or a value or range between any two of the above values.

[0063] In some embodiments, in step S150 ′, the electrostatic processing process includes at least one of electrostatic spraying and electrostatic spinning.

[0064] In the present application, the principle of electrostatic spraying is similar to the principle of electrostatic spinning process. A high-voltage electrostatic field is established between a polymer solution and a receiving device, and the polymer solution is squeezed out to form droplets. After the high-voltage electrostatic field is applied, an electrostatic field force is formed inside the droplets. When the electrostatic field force overcomes the surface tension of the droplets, unstable bursts will occur to form charged droplets at the micro-nano level. The solvent of the charged droplets is usually a volatile solvent. After the solvent evaporates, the charged droplets solidify into micro-nano particles and are deposited on the receiving device.

[0065] It should be noted that the main difference between electrostatic spraying and electrostatic spinning lies in the different solution properties and process parameters. The polymer solution generally used in electrostatic spraying has a lower viscosity, and the droplets evaporate and solidify to form micro-nano particles, while the polymer solution generally used in electrostatic spinning has a higher viscosity, and the droplets evaporate and solidify to form micro-nano fibers. Therefore, the key processing parameters for making a stent adhered with a degradable microsphere / fiber layer are the solution properties and process parameters. The receiving device is a stent body fixed inside the electrostatic spraying / spinning.

[0066] In some embodiments, the core layer degradable adhesive and the shell layer solution are fixed inside the electrostatic spraying / electrospinning device, the core layer degradable adhesive is connected to the core layer of the coaxial electrospinning nozzle, and the shell layer solution is connected to the shell layer of the coaxial electrospinning nozzle. The preparation of core-shell structured micro-nano particles / fibers is achieved by adjusting the solution properties such as polymer type, polymer molecular weight, solvent type, solution concentration, and process parameters such as voltage, droplet extrusion speed, receiving distance, ambient temperature and humidity, etc.

[0067] In some embodiments, the parameters of the electrostatic processing process include a voltage of 4 kV to 30 kV, a receiving distance of 5 cm to 20 cm, an ambient temperature of 20° C. to 30° C., and an ambient humidity of 20% to 40%.

[0068] In some embodiments, when the electrostatic processing technology is electrostatic spraying, the parameters include a voltage of 4 kV to 10 kV, a receiving distance of 10 cm to 14 cm, an ambient temperature of 20° C. to 30° C., and an ambient humidity of 20% to 40%.

[0069] In some embodiments, when the electrostatic processing process is electrospinning, the parameters include a voltage of 12 kV to 20 kV, a receiving distance of 16 cm to 20 cm, an ambient temperature of 20° C. to 30° C., and an ambient humidity of 20% to 40%.

[0070] In the third aspect of the present application, a biodegradable stent system is provided, which includes the biodegradable stent of the first aspect of the present application or the biodegradable stent prepared by the method of the second aspect of the present application and a medical dilation tube; further, the medical dilation tube may include a balloon dilation catheter.

[0071] In the present application, the balloon dilatation catheter may be selected from but not limited to one or more of a coronary artery balloon dilatation catheter, a peripheral vascular balloon dilatation catheter, a biliary balloon dilatation catheter, and a urogenital tract balloon dilatation catheter.

[0072] In some embodiments, a balloon dilatation catheter comprises a balloon and a catheter.

[0073] In some embodiments, the biodegradable stent system is applied to peripheral lower extremity arteries.

[0074] In a fourth aspect of the present application, a method for preparing the biodegradable stent system of the third aspect of the present application is provided, comprising crimping the biodegradable stent onto a medical expansion tube using a crimping device. Further, the crimping device can be a stent crimper or some crimping devices commonly used in the medical field.

[0075] Some examples are provided below.

[0076] The embodiments of the present application will be described in detail below in conjunction with examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods for which the conditions are not specified in the following examples are preferably referred to the guidance given in the present application, and can also be based on the experimental manual or normal conditions in the art, or can also be based on the conditions recommended by the manufacturer, or with reference to experimental methods known in the art.

[0077] In the following examples, the measured parameters of raw material components may have slight deviations within the range of weighing accuracy unless otherwise specified. For temperature and time parameters, acceptable deviations caused by instrument testing accuracy or operating accuracy are allowed.

[0078] Example 1

[0079] S1. Preparation of the stent body

[0080] Polylactic acid is selected as the main material, and laser engraving technology is used to process the degradable polylactic acid stent.

[0081] S2. Preparation of degradable adhesive microsphere layer by electrostatic spraying

[0082] Polylactide with a molecular weight of 10000-20000Da was dissolved in hexafluoroisopropanol to obtain a shell solution with a mass fraction of 1%, and butyl cyanoacrylate was selected as a core layer degradable adhesive. The core layer degradable adhesive was connected to the core layer of the coaxial electrospinning nozzle, and the shell solution was connected to the shell layer of the coaxial electrospinning nozzle.

[0083] The degradable polylactic acid scaffold prepared by S1 was fixed inside the electrospinning device and electrostatic spraying was performed according to the following parameters: voltage 4-6kV, receiving distance 12-14cm, ambient temperature 22-24℃, ambient humidity 35-40%. The prepared core-shell structure microspheres were deposited on the degradable polylactic acid scaffold, and the size of the core-shell structure microspheres was 10µm.

[0084] S3. Preparation of the scaffold system

[0085] The degradable stent prepared by S2 is pressed and gripped on the surface of the balloon of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0086] Example 1 Comparative Example

[0087] S1. Preparation of the stent body

[0088] Polylactic acid is selected as the main material, and laser engraving technology is used to process the degradable polylactic acid stent.

[0089] S2. Preparation of the scaffold system

[0090] The degradable stent prepared by S1 is pressed and gripped on the surface of the balloon of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0091] Example 2

[0092] S1. Preparation of the stent body

[0093] Polycaprolactone was selected as the main material, and 3D printing technology was used to process the degradable polycaprolactone scaffold.

[0094] S2. Preparation of degradable adhesive fiber layer by electrospinning

[0095] The polyglycolide-lactide copolymer with a molecular weight of 150000-250000Da was dissolved in acetone and N,N-dimethylformamide with a volume ratio of 8:2 to obtain a shell solution with a mass fraction of 6%, and octyl cyanoacrylate was selected as the core layer degradable adhesive. The core layer degradable adhesive was connected to the core layer of the coaxial electrospinning nozzle, and the shell solution was connected to the shell layer of the coaxial electrospinning nozzle.

[0096] The degradable polylactic acid scaffold prepared in S1 was fixed inside the electrospinning equipment and electrospinning was performed according to the following parameters: voltage 12-16 kV, receiving distance 18-20 cm, ambient temperature 26-28 ° C, ambient humidity 20-25%. The prepared core-shell structure fiber was deposited on the degradable polycaprolactone scaffold.

[0097] S3. Preparation of the scaffold system

[0098] The degradable stent prepared by S2 is pressed and gripped on the surface of the balloon of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0099] Example 2 Comparative Example

[0100] S1. Preparation of the stent body

[0101] Polycaprolactone was selected as the main material, and 3D printing technology was used to process the degradable polycaprolactone scaffold.

[0102] S2. Preparation of the scaffold system

[0103] The degradable stent prepared by S1 is pressed and gripped on the balloon surface of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0104] Example 3

[0105] S1. Preparation of the stent body

[0106] Polydioxanone was selected as the main material, and weaving technology was used to process the degradable polydioxanone stent.

[0107] S2. Preparation of degradable adhesive fiber layer by electrospinning

[0108] A polyglycolide-lactide copolymer with a molecular weight of 80,000-120,000 Da was dissolved in hexafluoroisopropanol to obtain a shell solution with a mass fraction of 10%, and butyl cyanoacrylate was selected as a core layer degradable adhesive. The core layer degradable adhesive was connected to the core layer of the coaxial electrospinning nozzle, and the shell solution was connected to the shell layer of the coaxial electrospinning nozzle.

[0109] The degradable polydioxanone scaffold prepared in S1 was fixed inside the electrospinning equipment and electrospinning was performed according to the following parameters: voltage of 16-20 kV, receiving distance of 18-20 cm, ambient temperature of 20-22 ° C, and ambient humidity of 30-35%. The prepared core-shell structure fiber was deposited on the degradable polydioxanone scaffold.

[0110] S3. Preparation of the scaffold system

[0111] The degradable stent prepared by S2 is pressed and gripped on the surface of the balloon of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0112] Example 3 Comparative Example

[0113] S1. Preparation of the stent body

[0114] Polydioxanone was selected as the main material, and weaving technology was used to process the degradable polydioxanone stent.

[0115] S2. Coating process for preparing water-soluble coating

[0116] Polyethylene glycol with a molecular weight of 80000-120000Da is dissolved in purified water to obtain a water-soluble coating solution with a mass fraction of 10%, and butyl cyanoacrylate is selected as a degradable adhesive. A degradable adhesive layer is first coated on the surface of the degradable stent prepared in S1, and then a water-soluble coating is coated on the surface of the degradable adhesive layer.

[0117] S3. Preparation of the scaffold system

[0118] The degradable stent prepared by S2 is pressed and gripped on the surface of the balloon of the balloon dilatation catheter system to complete the processing of the degradable stent system.

[0119] Experimental testing

[0120] 1. Effectiveness test

[0121] With reference to YY / T 0663.1-2021 Cardiovascular implants, intravascular devices, part 1: test methods for displacement in intravascular prostheses, the simulated blood vessel was placed in a 37°C PBS buffer environment, the balloon was expanded in the simulated blood vessel to release the stent, and the stent was pulled out of the simulated blood vessel at a speed of 50 mm / min to record the peak force. The results are shown in Table 1 below. The peak force of the stent deposited with the degradable adhesive microsphere / fiber layer is much higher than that of the stent without deposition, and the anti-displacement effect is excellent.

[0122] Table 1 Displacement peak force test results

[0123]

[0124] 2. Advantages over other methods

[0125] The samples of Example 3 and the control example of Example 3 were placed in a 37°C constant temperature shaking incubator to release butyl cyanoacrylate at 1, 3, 7, 12, 36, 24, and 48 hours, and the amount of butyl cyanoacrylate released was detected by gas chromatography. Figure 1 As shown, at 48 hours, the amount of butyl cyanoacrylate released from the stent of Example 3 is about 12%, which ensures the adhesion performance while achieving slow release. The degradation period of the adhesive layer is more than 6 months, and the stent can be wrapped into the blood vessel by the endothelium, with a lower risk of displacement. However, the butyl cyanoacrylate in the control stent of Example 3 has been completely released at 5 hours, with a risk of sudden release.

[0126] In summary, compared with the barb fixation process, the method of this application will not cause damage to the blood vessel wall and avoid complications such as dissection. Compared with the sudden release of adhesive that may be caused by directly applying the adhesive or covering the surface of the adhesive with a water-soluble layer, the adhesive of the method of this application is a core-shell structure, and the adhesive of the core layer is gradually released, reducing the occurrence of ectopic embolism caused by the adhesive freeing the target area. In addition, the adhesive has good biocompatibility and can be completely degraded after the stent is endothelialized and does not remain in the body.

[0127] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0128] The above-mentioned embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for a person of ordinary skill in the art, several variations 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 shall be subject to the attached claims, and the description may be used to interpret the scope of the claims.

Claims

1. A biodegradable stent, characterized in that: The biodegradable stent comprises a stent body and a degradable material coated on the surface of the stent body, wherein the degradable material is a core-shell structure, the core layer of the core-shell structure is a degradable adhesive layer, the shell layer is a degradable polymer layer, and the degradable adhesive layer comprises cyanoacrylate.

2. The biodegradable stent according to claim 1, characterized in that: The degradable material coated on the surface of the stent body is selected from one or more of degradable adhesive microspheres and degradable fiber layers.

3. The biodegradable stent according to claim 2, characterized in that: The cyanoacrylate includes one or more of methyl cyanoacrylate, ethyl cyanoacrylate, propyl cyanoacrylate, butyl cyanoacrylate, pentyl cyanoacrylate, hexyl cyanoacrylate, heptyl cyanoacrylate and octyl cyanoacrylate; The degradable polymer layer comprises a degradable polymer with a molecular weight of 5000Da to 500000Da; the degradable polymer is selected from at least one of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol, and / or the degradable polymer is selected from a plurality of copolymers of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol.

4. The biodegradable stent according to claim 1, characterized in that: The material of the stent body is a biodegradable material; the biodegradable material includes one or more of synthetic materials and natural materials; Wherein, the synthetic material includes at least one of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol, and / or, the synthetic material includes multiple copolymers of polylactide, polyglycolide, polycaprolactone, polydioxanone, polytrimethylene carbonate and polyethylene glycol; the natural material includes at least one of collagen, silk fibroin, chitin, chitosan, hyaluronic acid and sodium alginate.

5. A method for preparing the biodegradable stent according to any one of claims 1 to 4, characterized in that: The following steps are involved: preparing a stent body; The degradable material with a core-shell structure is deposited on the surface of the stent body.

6. The method according to claim 5, characterized in that The step of preparing the stent body includes preparing the stent body by at least one of laser engraving, weaving and 3D printing.

7. The method according to claim 6, characterized in that The degradable material with core-shell structure is prepared from a degradable binder and a shell layer solution by at least one of electrostatic spraying and electrostatic spinning.

8. The method according to claim 7, characterized in that The method satisfies one or more of the following conditions: (1) The shell solution comprises a degradable polymer and an organic solvent, wherein the organic solvent comprises one or more of hexafluoroisopropanol, dichloromethane, chloroform, N,N-dimethylformamide, tetrahydrofuran, ethanol, acetic acid, acetone, n-propyl acetate and n-butyl acetate; (2) The mass fraction of the degradable polymer in the shell solution is 0.5% to 15%; (3) The parameters of the electrostatic spraying include: voltage of 4 kV~10 kV, receiving distance of 10 cm~14 cm, ambient temperature of 20°C~30°C, and ambient humidity of 20%~40%; (4) The parameters of the electrospinning include: voltage of 12 kV to 20 kV, receiving distance of 16 cm to 20 cm, ambient temperature of 20°C to 30°C, and ambient humidity of 20% to 40%.

9. A biodegradable stent system, characterized in that: It comprises the biodegradable stent described in any one of claims 1 to 4 or the biodegradable stent prepared by the method described in any one of claims 5 to 8 and a medical dilatation tube; the medical dilatation tube comprises a balloon dilatation catheter; the balloon dilatation catheter comprises a balloon and a catheter.

10. A method for preparing the biodegradable stent system according to claim 9, characterized in that: The method comprises using a crimping device to crimp the biodegradable stent onto a medical expansion tube.

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