CN111529150B

CN111529150B - Sinus duct stent and preparation method thereof

Info

Publication number: CN111529150B
Application number: CN202010353321.5A
Authority: CN
Inventors: 白晶; 王先丽; 程兆俊; 邵怡; 薛烽; 储成林; 汪丰
Original assignee: Southeast University Suzhou Medical Device Research Institute
Current assignee: Southeast University Suzhou Medical Device Research Institute
Priority date: 2020-04-28
Filing date: 2020-04-28
Publication date: 2023-02-24
Anticipated expiration: 2040-04-28
Also published as: CN111529150A

Abstract

The invention provides a nasal sinus duct stent and a preparation method thereof. The preparation method comprises the following steps: providing a preset thermoplastic degradable polymer, printing the thermoplastic degradable polymer into a slice on an XOY plane by adopting a 3D printing technology, curling the slice into an annular structure around a preset reference axis, performing heat treatment setting on the annular structure after the slice is pre-fixed to obtain a hollow stent, forming a porous drug carrying layer on the surface of the hollow stent, and performing hole sealing treatment on the porous drug carrying layer to obtain the sinus duct stent. The preparation method provided by the invention is not limited by the precision of a fused deposition type 3D printer instrument, ensures the consistency of the forming conditions of each part of the bracket, so that the bracket has good elasticity, can effectively prevent the bracket from escaping from a matrix and subsequent sudden release of the medicament in the deployment process, and simultaneously avoids the problem of insufficient medicament loading capacity, thereby achieving the purpose of preventing the occurrence of medical accidents such as secondary blockage and the like caused by the proliferation of the granulation tissue of the nasal cavity into the nasal cavity space.

Description

Sinus duct stent and preparation method thereof

Technical Field

The invention belongs to the technical field of biomedical equipment, and particularly relates to a sinus duct stent and a preparation method thereof.

Background

Human nasal obstruction is a common disease in clinic. It often causes the patient to breathe unsmoothly, even causes facial deformity and paralysis, and directly influences the normal life of people. The main method of the current interventional therapy is to send an elution stent with a drug on the surface into a blocked nasal cavity part by using a catheter delivery system, so that the narrow nasal cavity is expanded and the repair function can be achieved by using the drug effect.

The prior stent preparation technology has the defects that: the requirements of nasal cavities of different individuals on the size of the bracket are different, the bracket prepared by the traditional method has low efficiency, poor repeatability and difficulty in timely adjustment of the size, the bracket with the hollowed side surface prepared by the laser engraving method has high cost and the wall thickness is not easy to control. With the rise of 3D printing technology, the modern molding technology with low cost, no raw material waste, high efficiency and good repeatability is widely applied to the preparation of medical instruments. For the preparation of tubular stents, the following disadvantages exist with conventional Z-stacking techniques: (1) The preparation of the bracket with small diameter and a complex pattern structure on the surface is difficult to realize due to the limitation of instrument precision; (2) The wall thickness of the bracket prepared by stacking in the Z-axis direction is required to be thicker, otherwise, the requirement of higher vertical stacking height is difficult to realize; (3) The limitation of the wall thickness causes that the high polymer material stent prepared by stacking in the Z-axis direction in 3D printing is hard and brittle and has almost no self-expansion performance.

At present, a 3D printing support with good product performance is prepared by Chinese patent CN 102149859B in one of the prior art, the support is prepared by a 3D 4 shaft rapid forming system, although the printed support can meet the requirement of self-expansion performance, the requirement on the precision and the type of a 3D printer is higher, the diameter change of the support is not easy, and the improvement of the equipment cost is not different from the increase of the overall cost of a sinus duct support. In addition, although the ultraviolet curing molding (SLA) combined Continuous Liquid Interface Production (CLIP) technology adopted in the above patent can realize the preparation of the ultrafine vascular stent, the method requires the use of precise instruments. In addition, the rapid curing of the photosensitive resin by ultraviolet light-initiated photopolymerization requires the addition of potentially toxic chemical agents such as photoinitiators to the printing ink. In addition, the SLA raw material is photosensitive resin, when a body-shaped structure is formed to achieve the purpose of curing, the degradation mechanism of the cured resin material applied to the human body is no longer the bond breaking mechanism of a linear polymer material, the degradation mechanism is the typical mechanism of water absorption and swelling of a body-shaped high polymer material, and the risk of inducing potential safety hazards after the SLA raw material is implanted into the human body exists, so that the preparation method has no universality.

The 3D printing technology is well known for its high efficiency, and fused deposition type 3D printers require that polymer is sprayed from a nozzle and deposited on a hot bed, and then rapidly cooled and solidified to enable the next layer to be stacked. For semi-crystalline polymeric materials, the degree of crystallinity depends on how fast the sample is going to be melted to cool. When the polymer material is cooled at a fast speed in the 3D printing rapid forming process, the prepared stent product has the problems of high brittleness and the like.

The high polymer material has viscosity after reaching the melting point temperature, and can play a role in bonding two adjacent matrixes, but for the support, after two welding edges are simply welded, the support can generate stress concentration when stressed, and the welding edges can be firstly broken to cause the support to lose efficacy and not play a supporting role; the general polymer material is a hydrophobic material, and has weak binding capacity with the drug, so that the drug is difficult to bind with the stent main body, the drug is often released suddenly, the therapeutic purpose cannot be achieved, and the drug poisoning of a patient can be caused.

The balloon method adopted in the existing stent deployment scheme can cause huge mechanical destructive damage to the lumen, and risks of scratching and even breaking the lumen wall exist. In particular, during deployment of a polymer-based luminal stent, the stent can undergo a severe plastic deformation process; at this time, if the drug is carried on the surface of the stent, the drug coating is easily peeled off, and thus, after the stent is implanted into a lesion of a human body, the total dose may be insufficient, so that it is difficult to ensure the therapeutic effect of the interventional stent.

For the reasons, the preparation method of the bracket customized according to different human nasal cavity environments is worthy of being researched by vast medical workers. The support wall that 3D printed method was made is too thick and inelastic in Z axle direction stacking, tubular 3D printed method requires too high and difficult acquisition to instrument itself, and increased the cost of support, the support that the photocuring was printed possesses very big medical risk because of the restriction of raw materials is implanted in the human body, and, the degradation cycle and the tissue healing cycle of support are asynchronous, the welding limit that hot gas welding caused is cracked by stress concentration, key technical problems such as speed and the dose control of medicine release need to be solved urgently.

Disclosure of Invention

The invention aims to at least solve one of the technical problems in the prior art and provides a sinus duct stent and a preparation method thereof.

The invention provides a preparation method of a sinus duct stent, which comprises the following specific steps:

providing a preset thermoplastic degradable polymer, and printing the thermoplastic degradable polymer into a thin sheet on an XOY plane by adopting a 3D printing technology;

coiling the thin slice around a preset reference shaft to form an annular structure, and after the thin slice is pre-fixed, carrying out heat treatment setting on the annular structure to obtain a hollow bracket;

forming a porous drug-carrying layer on the surface of the hollow stent;

and carrying out hole sealing treatment on the porous medicine carrying layer to obtain the sinus duct stent.

Optionally, after the pre-fixing, performing heat treatment setting on the annular structure to obtain a hollow stent, including:

carrying out heat treatment setting on the annular structure at 40-50 ℃ for 2-5 min to obtain a semi-finished hollow bracket;

and preparing and forming a reinforcing rib on the semi-finished hollow support to obtain the hollow support.

Optionally, the preparing and forming a reinforcing rib on the semi-finished hollow support to obtain the hollow support includes:

and melting the welding areas on the two sides of the semi-finished hollow support, applying welding pressure to form a spiral reinforcing rib wound on the outer surface of the semi-finished hollow support, and annealing at 40-50 ℃ for 5-20 min to obtain the hollow support.

Optionally, the forming a porous drug-carrying layer on the surface of the hollow stent includes:

immersing the hollow stent into 80-120 mL of mixed solution of drug and chitosan, ultrasonically immersing for 0.5-1.5 h, and then carrying out freeze drying treatment to enable the chitosan to crust on the surface of the hollow stent to form the porous drug carrying layer.

Optionally, the drug-chitosan mixed solution comprises acetic acid with a concentration range of 1% (v/v) to 3% (v/v), chitosan with a viscosity range of 400mPa · s to 600mPa · s, a concentration range of 1% (w/v) to 3% (w/v), and sirolimus drug; wherein the content of the first and second substances,

the sirolimus drug loading amount accounts for 10% (w/w) to 20% (w/w) of the total amount of the chitosan.

Optionally, the hole sealing treatment is performed on the porous drug carrying layer to obtain the sinus duct stent, including:

immersing the hollow stent with the porous drug-carrying layer into 80-120 mL of sodium alginate saturated aqueous solution, and dropwise adding the saturated aqueous solution into 80-120 mL of CaCl ₂ Mechanically stirring the solution for 5 to 15min to form calcium alginate hydrogel;

and sealing the porous drug-carrying layer by using the calcium alginate hydrogel, and carrying out freeze drying treatment to obtain the sinus duct stent.

Optionally, the thermoplastic degradable polymer comprises at least one of polylactic acid, polycaprolactone, polyglycolic acid, polylactic-glycolic acid.

Optionally, the sheet is a parallelogram-shaped sheet; wherein the content of the first and second substances,

any one of rhombus patterns, triangular patterns, trapezoid patterns and circular patterns penetrating through the thickness of the parallelogram sheet is arranged on the parallelogram sheet.

Optionally, the length range of the sheet is 10 mm-20 mm, the width range is 20 mm-30 mm, and the thickness range is 0.1mm-0.5 mm.

In a second aspect of the present invention, there is provided a sinus duct support, which is prepared by the above-mentioned sinus duct support preparation method.

The invention provides a preparation method of a sinus duct stent, which comprises the following steps: the method is characterized in that a preset thermoplastic degradable polymer is provided, the thermoplastic degradable polymer is printed out of a sheet on an XOY plane by adopting a 3D printing technology, and compared with a Z-axis direction stacking printing method, the sheet (equivalent to the side structure of a stent) printed on the XOY plane can be used for preparing a sinus duct stent with a small diameter and a wall thickness of 0.1-0.5 mm without being limited by the precision of a fused deposition type 3D printer instrument, so that the consistency of the molding condition of each part of the stent is ensured, and the stent has good elasticity. And then, curling the formed slices around a preset reference shaft to form an annular structure, pre-fixing the annular structure, carrying out heat treatment setting on the annular structure to obtain a hollow stent, forming a porous drug carrying layer on the surface of the hollow stent, and carrying out hole sealing treatment on the porous drug carrying layer to obtain the sinus duct stent. The medicine carrying layer formed in the embodiment increases the binding force between the medicine and the support through hole sealing treatment, prevents the falling of the medicine layer, effectively prevents the support from escaping from a matrix and subsequent sudden release of the medicine in the deployment process, and simultaneously avoids the problem of insufficient medicine carrying capacity so as to prevent the occurrence of medical accidents such as secondary blockage caused by the growth of the granulation tissue hyperplasia of the nasal cavity into the nasal cavity space.

Drawings

FIG. 1 is a flow chart of a method of manufacturing a sinus duct support according to a first embodiment of the present invention;

FIG. 2 is a side view of a sinus canal stent in accordance with a second embodiment of the present invention in a geometric configuration with lateral expansion of the ribs;

FIG. 3 is a schematic view of a sinus duct support according to a third embodiment of the present invention showing the curling direction and the welding edges;

FIG. 4 is a perspective view and a top view of a sinus tube support according to a fourth embodiment of the present invention;

FIG. 5 is a graph showing a simulated stress analysis of a stent having a vertical welded edge and a helical welded edge according to a fifth embodiment of the present invention; wherein, the first and the second end of the pipe are connected with each other,

fig. 5 (a) and (b) are stress cloud diagrams of the bracket with the vertical welding edge under the simulation condition of simulating the nasal cavity wall pressure;

FIGS. 5 (c) and (d) are respectively a deformed cloud image of the simulated nasal cavity wall pressure of the stent with a spiral welding edge;

FIG. 6 is a scanning electron micrograph of a porous drug-bearing layer formed after dipping and freeze-drying a sinus stent according to a sixth embodiment of the present invention;

FIG. 7 is a radial compression-rebound graph of a sinus canal stent having an inner diameter of 6mm and varying wall thickness according to a seventh embodiment of the present invention.

Detailed Description

In order to make the technical solutions of the present invention better understood, the present invention is further described in detail with reference to the accompanying drawings and the detailed description below.

As shown in fig. 1, in a first aspect of the present invention, a method S100 for preparing a sinus canal stent is provided, which specifically includes the following steps S110 to S140:

and S110, providing a preset thermoplastic degradable polymer, and printing the thermoplastic degradable polymer into a sheet on an XOY plane by adopting a 3D printing technology.

Aiming at the problem that the diameter of the support prepared by the current 3D printing is not easy to change, and the wall thickness of the printed support is too thick and inelastic, the embodiment adopts a fused deposition type 3D printer to print the thermoplastic degradable polymer into a thin slice on an XOY plane, and the thin slice has a thin wall thickness and controllable diameter. Illustratively, and as shown in conjunction with FIG. 2, this embodiment provides the sheet as a parallelogram-shaped sheet having a length in the range of 10mm to 20mm, a width in the range of 20mm to 30mm, and a thickness in the range of 0.1mm to 0.5mm. That is, the thermoplastic degradable polymer is printed out by a 3D printer into a sheet model of a parallelogram structure, which corresponds to a side-deployed structure of the stent.

Further, the parallelogram sheet of the present embodiment may be a sheet of a side-unfolding model with patterns, that is, any one of a rhombus pattern, a triangle pattern, a trapezoid pattern and a circle pattern penetrating the thickness of the sheet is provided on the sheet, and as an example, as shown in fig. 2, the parallelogram sheet of the present embodiment is provided with a rhombus hollow pattern, but of course, patterns with other shapes may be selected, and this is not particularly limited.

The printing material of the present example is a thermoplastic degradable polymer containing at least one of polylactic acid, polycaprolactone, polyglycolic acid, and polylactic-glycolic acid. That is, any thermoplastic degradable polymer such as polylactic acid, polycaprolactone, polyglycolic acid, and polylactic-glycolic acid may be used as the thermoplastic degradable polymer, or a mixture of these may be used, and of course, other thermoplastic degradable polymers may be used, and they are not particularly limited.

The fused deposition type 3D printing rapid prototyping technology is adopted in the embodiment, the working efficiency is high, the repeatability is strong, the manufacturing cost is greatly reduced, the sinus duct support with the small diameter and the wall thickness of 0.1mm-0.5mm can be prepared by printing the side structure of the support on the XOY plane, the limitation of the precision of a fused deposition type 3D printer instrument is avoided, the consistency of the forming condition of each part of the support is ensured, and the support of the embodiment has good elasticity.

And S120, curling the sheet printed in the step S110 into a ring-shaped structure around a preset reference shaft, and performing heat treatment setting on the ring-shaped structure after pre-fixing to obtain the hollow bracket.

It should be noted that the method of coiling the sheet into the annular structure is not particularly limited in this example, for example, a metal rod may be provided, the sheet may be coiled into the annular structure by winding the sheet around the metal rod, and of course, the metal rod may need to be taken out after the annular structure is shaped to obtain the hollow stent, and the size of the metal rod may be specifically selected according to the diameter of the hollow stent, and a copper rod having a diameter in a range of 3mm to 6mm is used in this embodiment.

It should be further noted that the reference axis is not specifically limited in this embodiment, and for example, as shown in fig. 2, a line (004) in fig. 2 is a reference axis (a secondary inversion axis), (005) and (005 ') and (006') are coincident points of a top end and a bottom end of a parallelogram side sheet structure formed by welding, (002) is a skeleton portion of a stent network structure, and (003) is a hot-air welding edge. In the embodiment, as shown in fig. 3, the line (004) of the parallelogram sheet is used as a central axis to be curled, and after hot-gas welding forming, the top end point (005) is overlapped with the point (005 '), the bottom end point (006) is overlapped with the point (006'), and the corresponding two sides (003) are used as welding areas, and after welding, an integrated hollow stent is formed, and the formed hot-gas welding edge is spiral.

Specifically, step S120 of this embodiment specifically includes: and (3) coiling the parallelogram thin sheet around a copper rod for a circle according to a reference shaft (004), pre-fixing two ends and the middle area of the thin sheet by using thin copper wires to form a ring structure, and then putting the ring structure into a vacuum drying oven at the temperature of 40-50 ℃ for heat treatment and shaping for 2-5 min to form the hollow support. The hollow support can be specifically set according to actual needs, namely, the diameter of the hollow support can be changed by selecting copper rods with different diameters, the diameter of the support is easy to change, and the method is low in cost.

This embodiment is printed prefabricated support side expansion structure with 3D and is combined with hot gas welding's technique, can prepare out the support of different diameters and wall thickness scope to satisfy the individual demand to support size, radial holding power, elasticity and compliance of different patients, and, the radial holding power and the accessible support wall thickness adjustment of rebound rate of this support.

Furthermore, in order to avoid stress concentration of the bracket when the bracket is stressed after the two welding edges are welded, the welding edges are firstly broken to cause the failure of the bracket and fail to play a supporting role, the embodiment forms the reinforcing ribs in the welding areas so as to obtain the integrated hollow bracket.

Specifically, referring to fig. 4, after the annular structure is heat-treated and shaped at 40-50 ℃ for 2-5 min, the method further comprises preparing and forming a reinforcing rib (001) on the hollow support to obtain an integrated hollow support, wherein the cross section of the integrated hollow support is a hollow cylinder. As shown in fig. 2 and fig. 3, the steps specifically include: and melting the welding areas (003) on the two sides of the semi-finished hollow bracket after heat treatment and shaping, applying welding pressure to the welding areas (003) to form a spiral reinforcing rib (001) wound on the outer surface of the semi-finished hollow bracket, and then annealing at 40-50 ℃ for 5-20 min to obtain the hollow bracket.

In this embodiment, since the reinforcing ribs are further formed in the welding region of the bracket, it is necessary to take out the copper bar after forming the integral hollow bracket having the reinforcing ribs.

This embodiment has not only realized applying welding pressure to the welding area through forming the strengthening rib and has reached the purpose that the welding is tight real, has still guaranteed the radial elasticity of support through forming the spiral strengthening rib, has guaranteed simultaneously that the support is unlikely to early fracture and inefficacy when receiving nasal cavity wall pressure grip, thereby prevent effectively that the support position of fracture department in advance from causing great block to drop and leading to narrow nasal cavity jam once more originally, further worsen respiratory tract environment. In addition, compared with the support with the vertical reinforcing ribs, the support with the spiral reinforcing ribs has the advantages that the maximum wall pressure and the maximum deformation of the support under the same stress condition are obviously reduced, and the smooth breathing and the beautiful appearance of a patient after the support is implanted are ensured.

Furthermore, the annealing treatment on the thermoplastic polymer material adopted by the embodiment can release the internal stress of the stent caused during the crimping, improve the bonding strength of the welding seam, and increase the crystallinity of the polymer by controlling the annealing temperature and time parameters, so that the brittleness of the raw material is improved, and the stent has good elasticity and meets the service requirement.

S130, forming a porous drug carrying layer on the surface of the hollow stent, and specifically comprising the following steps:

immersing the hollow stent into 80-120 mL of mixed solution of drug and chitosan, ultrasonically immersing for 0.5-1.5 h, and then carrying out freeze drying treatment to enable the chitosan to crust on the surface of the hollow stent to form a porous drug carrying layer.

The drug of the present embodiment can be selected according to actual needs, and the drug-chitosan mixed solution of the present embodiment includes acetic acid at a concentration ranging from 1% (v/v) to 3% (v/v), chitosan at a viscosity ranging from 400mPa · s to 600mPa · s and at a concentration ranging from 1% (w/v) to 3% (w/v), and sirolimus drug; wherein, the sirolimus drug loading amount accounts for 10% (w/w) to 20% (w/w) of the total amount of the chitosan, namely, the sirolimus drug is loaded in the porous of the chitosan, and the chitosan is encrusted on the surface of the hollow stent to form the porous drug loading.

In the embodiment, the porous drug carrying layer is formed on the hollow stent formed by 3D printing through outer layer dipping and freeze drying, and compared with the traditional direct spraying method, the process increases the binding force between the drug and the stent, so that the drug layer cannot fall off.

S140, hole sealing treatment is carried out on the porous medicine carrying layer to obtain the sinus duct support, and the method specifically comprises the following steps:

immersing the hollow stent with the porous drug carrying layer into 80-120 mL of sodium alginate saturated aqueous solution, and dropwise adding the solution into 80-120 mL of CaCl ₂ Mechanically stirring the solution for 5 to 15min to form calcium alginate hydrogel;

and (3) sealing the porous drug-carrying layer by using calcium alginate hydrogel, and carrying out freeze drying treatment to obtain the sinus duct stent.

In the embodiment, the porous drug carrying layer in the previous step is subjected to hole sealing treatment by adopting the calcium alginate hydrogel, so that the escape of the stent from the matrix and subsequent burst release of the drug are effectively prevented in the deployment process, namely, the drug loss in the conveying process is effectively reduced, the problem of insufficient drug carrying capacity is avoided, and the probability of occurrence of medical accidents such as secondary blockage caused by the fact that the nasal cavity granulation tissue grows into the nasal cavity space is also prevented. The porous structure of the sinus duct stent shell of the embodiment creates a space for the radial elastic expansion of the stent, thereby greatly reducing the probability of stent displacement after the stent is successfully deployed.

The invention aims to improve the efficiency of the prior art, reduce the manufacturing cost of the stent, and prepare the sinus duct stent which is matched with a patient in size, has good toughness, can be completely degraded, and can inhibit granulation tissue hyperplasia and prevent sudden release and falling of the drug. The preparation method solves the problems that the size of a fused deposition type 3D printing technology for preparing the bracket is limited and the brittleness of a finished product is large, and simultaneously effectively avoids the problems of stress concentration, easy falling of a loaded medicine layer, sudden release of the medicine and the like caused by the existence of a vertical welding seam on the bracket, and achieves the purpose of supporting a collapsed nasal cavity and inhibiting granulation tissue from proliferating and growing into the nasal cavity space.

The method of making the sinotubular stent will be further described with reference to several specific examples below:

example 1

The preparation method of the sinus duct stent in the present example comprises the following steps:

s1, establishing a support side structure model by using three-dimensional modeling software, exporting a file format of stl file, importing the stl file into a fused deposition type 3D printer, and printing a side unfolding structure sheet model which is provided with patterns and is in a parallelogram shape by using polycaprolactone (Mv =40, 000, PCL) as a raw material, namely printing a sheet. The specific parameters of the side structure of the parallelogram sheet printed in this embodiment are as follows: length L =10.0mm, width W =20mm, and sheet thickness t =0.1mm.

S2, coiling the parallelogram slices obtained in the step S1 for one circle around a thin copper rod with the diameter of 3.0mm according to a preset direction (refer to a line 004 in a figure 2), pre-fixing two welded ends (refer to a line 003 in the figure 2) and the middle of the parallelogram slices with thin copper wires, and putting the parallelogram slices into a vacuum drying oven at the temperature of 40 ℃ for first heat treatment and shaping for 2min to form a semi-finished hollow bracket.

Furthermore, after the obtained semi-finished hollow bracket is taken out, a hot gas welding technology is adopted, hot gas reaching the melting point temperature is used for melting two sides of the degradable polymer parallelogram slice together, and welding pressure is applied to a welding area to achieve the purpose of tight welding. And after the hot gas welding is finished, placing the support accompanied with the fine copper rod support into a vacuum drying oven at 45 ℃ for secondary annealing treatment for 5min, and extracting the copper rod to obtain the hollow support with firm combination.

And S3, immersing the stent obtained in the step S2 in 100mL of sirolimus-chitosan mixed solution, ultrasonically soaking for 1h to enable the solvent to volatilize, then, taking out the hollow stent, and performing freeze drying treatment to form a porous supporting layer on the surface of the hollow stent. The solution system of the embodiment uses acetic acid as a solvent, the viscosity of the used chitosan is 400 mPas, the concentration of the chitosan solution is 2% (w/v), the solvent acetic acid is a 2% (v/v) aqueous solution, and the sirolimus supporting amount accounts for 10% (w/w) of the total amount of the chitosan.

S4, immersing the hollow stent with the porous drug carrying layer obtained in the step S3 into 100mL of sodium alginate saturated aqueous solution, and dropwise adding 100mL of CaCl by using a 21-gauge needle (21-G) ₂ The solution (1.0%, w/v) was mechanically stirred for 10 minutes to allow the calcium alginate hydrogel to seal the porous layer on the surface of the stent, and then the hydrogel was freeze-dried and stored in a thermostat at 4 ℃ to obtain a sinus duct stent.

Further, since the welding edge of the sinus canal stent formed in the embodiment is spiral, correspondingly, the formed reinforcing rib is also spiral, which has a certain difference from the conventional vertical welding edge. Therefore, the present embodiment further analyzes the simulated force analysis diagram of the sinus canal support with the vertical welding edge and the spiral welding edge. Specifically, as shown in fig. 5, (a) and (b) in fig. 5 are respectively stress cloud graphs of the bracket with the vertical welding edge under the simulation of the nasal cavity wall pressure; 5 (c) and (d) in the figure are respectively deformation cloud pictures under the simulation condition of the wall pressure of the bracket simulation nasal cavity with the spiral welding edge. As can be known from analog simulation analysis, compared with a vertical reinforcing rib, the support with the spiral welding edge has smaller deformation displacement, the spiral reinforcing rib effectively disperses the pressure and holding force to the periphery of the support wall, and the support with the spiral reinforcing rib has the advantages that the maximum wall pressure and the maximum deformation of the support are obviously reduced under the same stress condition compared with the support with the vertical reinforcing rib.

Furthermore, when the scanning electron microscope image is further analyzed by taking the sinus duct stent formed in the embodiment as an example, as shown in fig. 6, a loose and porous chitosan shell layer is formed on the surface of the polymer-based stent, wherein larger pores in the chitosan shell layer can be used for carrying the drug and have higher biological safety.

Example 2

s1, establishing a stent side structure model by using three-dimensional modeling software, exporting a file format of stl file, importing the stl file into a fused deposition type 3D printer, and printing a side unfolding structure sheet model which is provided with patterns and has a parallelogram shape by using poly (lactic-co-glycolic acid) (Mv =80,000,PLGA) as a raw material, namely printing a sheet. The specific parameters of the side structure of the parallelogram sheet printed in this embodiment are as follows: length L =13.0mm, width W =25.0mm, and sheet thickness t =0.2mm.

And S2, coiling the parallelogram slices obtained in the step S1 around a thin copper rod with the diameter of 4.0mm for one circle according to a preset direction (refer to a line 004 in a figure 2), pre-fixing the welded two ends (refer to a line 003 in the figure 2) and the middle part by using a thin copper wire, and putting the obtained product into a vacuum drying oven at the temperature of 45 ℃ for primary heat treatment and shaping for 3min to form a semi-finished hollow support.

Furthermore, after the obtained semi-finished hollow bracket is taken out, a hot gas welding technology is adopted, hot gas reaching the melting point temperature is used for melting two sides of the degradable polymer parallelogram slice together, and welding pressure is applied to a welding area to achieve the purpose of tight welding. And after the hot gas welding is finished, placing the support accompanied with the fine copper rod support into a vacuum drying oven at 45 ℃ for secondary annealing treatment for 10min, and extracting the copper rod to obtain the hollow support with firm combination.

And S3, immersing the stent obtained in the step S2 in 100mL of sirolimus-chitosan mixed solution for 1 hour of ultrasonic immersion to allow the solvent to volatilize and then the chitosan to form a shell on the surface of the stent, and then taking out the stent for freeze drying treatment to form a porous supporting layer on the surface of the hollow stent. In the solution system of the present embodiment, acetic acid is used as a solvent, the viscosity of the used chitosan is 500mPa · s, the concentration of the chitosan solution is 2% (w/v), the solvent acetic acid is a 2% (v/v) aqueous solution, and the sirolimus loading accounts for 10% (w/w) of the total amount of chitosan.

S4, immersing the hollow stent with the porous drug carrying layer obtained in the step S3 into 100mL of sodium alginate saturated aqueous solution, and dropwise adding 100mL of CaCl by using a 21-gauge needle (21-G) ₂ Mechanically stirring the solution (1.0%, w/v) for 10min to seal the porous layer on the surface of the stent, freeze-drying, and standing at 4 deg.CStored in a thermostat to obtain a sinus duct stent.

Example 3

s1, establishing a stent side structure model by using three-dimensional modeling software, exporting a file format of stl file, importing the file format of stl file into a fused deposition type 3D printer, and printing a side unfolding structure sheet model which is provided with patterns and is in a parallelogram shape by using polylactic-glycolic acid (Mv =100,000,PLGA) as a raw material. I.e. a sheet is printed out. The specific parameters of the side structure of the parallelogram sheet printed in this embodiment are as follows: length L =16.0mm, width W =30.0mm, and sheet thickness t =0.3mm.

And S2, coiling the parallelogram slices obtained in the step S1 around a thin copper rod with the diameter of 5.0mm for one circle according to a preset direction (refer to a line 004 in a figure 2), pre-fixing the welded two ends (refer to a line 003 in the figure 2) and the middle part by using a thin copper wire, and putting the obtained product into a vacuum drying oven at the temperature of 45 ℃ for primary heat treatment and shaping for 5min to form a semi-finished hollow support.

Furthermore, after the obtained hollow bracket semi-finished product is taken out, a hot gas welding technology is adopted, hot gas reaching the melting point temperature is used for melting two sides of the degradable polymer parallelogram slice together, and welding pressure is applied to a welding area to achieve the purpose of tight welding. And after the hot gas welding is finished, placing the support accompanied with the fine copper rod support into a vacuum drying oven at 45 ℃ for secondary annealing treatment for 15min, and extracting the copper rod to obtain the firmly-combined hollow support.

And S3, immersing the stent obtained in the step S2 into 100mL of sirolimus-chitosan mixed solution, ultrasonically soaking for 1h to enable the solvent to volatilize, then, taking out the stent, and performing freeze drying treatment to form a porous supporting layer on the surface of the hollow stent. In the solution system of the present embodiment, acetic acid is used as a solvent, the viscosity of the used chitosan is 600mPa · s, the concentration of the chitosan solution is 2% (w/v), the solvent acetic acid is a 2% (v/v) aqueous solution, and the sirolimus loading accounts for 10% (w/w) of the total amount of chitosan.

S4, loading the porous medicine obtained in the step S3The carrier layer hollow stent was immersed in 100mL of a saturated aqueous solution of sodium alginate, and 100mL of CaCl was added dropwise with a 21-gauge needle (21-G) ₂ In the solution (1.0%, w/v), the calcium alginate hydrogel was mechanically stirred for 10 minutes to seal the porous layer on the surface of the stent, and then the calcium alginate hydrogel was freeze-dried and stored in a thermostat at 4 ℃ to obtain a sinus duct stent.

Example 4

s1, establishing a side structure model of the stent by using three-dimensional modeling software, exporting a file format of stl file, importing the stl file into a fused deposition type 3D printer, and printing a side unfolding structure sheet model which is provided with patterns and is in a parallelogram shape by using polylactic-glycolic acid (Mv =200,000,PLGA) as a raw material. I.e. a sheet is printed out. The specific parameters of the side structure of the parallelogram sheet printed in this embodiment are as follows: length L =19.0mm, width W =30.0mm, and sheet thickness t =0.5mm.

And S2, coiling the parallelogram slices obtained in the step S1 around a thin copper rod with the diameter of 6.0mm for one circle according to a preset direction (refer to a line 004 in a figure 2), pre-fixing the welded two ends (refer to a line 003 in the figure 2) and the middle part by using a thin copper wire, and putting the obtained product into a vacuum drying oven at the temperature of 50 ℃ for primary heat treatment and shaping for 5min to form a semi-finished hollow support.

Furthermore, the obtained semi-finished hollow bracket is taken out, a hot gas welding technology is adopted, the hot gas reaching the melting point temperature is used for melting the two sides of the degradable polymer parallelogram slices together, and welding pressure is applied to a welding area to achieve the purpose of tight welding. And after the hot gas welding is finished, placing the bracket accompanied with the fine copper rod support into a vacuum drying oven at 50 ℃ for secondary annealing treatment for 20min, and extracting the copper rod to obtain the firmly-combined hollow bracket.

And S3, immersing the stent obtained in the step S2 into 100mL of sirolimus-chitosan mixed solution, ultrasonically soaking for 1h to enable the solvent to volatilize, then, taking out the stent, and performing freeze drying treatment to form a porous supporting layer on the surface of the hollow stent. The solution system of the embodiment uses acetic acid as a solvent, the viscosity of the used chitosan is 600 mPas, the concentration of the chitosan solution is 2% (w/v), the solvent acetic acid is a 2% (v/v) aqueous solution, and the sirolimus supporting amount accounts for 10% (w/w) of the total amount of the chitosan.

S4, immersing the hollow stent with the porous drug-carrying layer obtained in the step S3 into 100mL of sodium alginate saturated aqueous solution, and dropwise adding 100mL of CaCl by using a 21-gauge needle (21-G) ₂ In the solution (1.0%, w/v), the calcium alginate hydrogel was mechanically stirred for 10 minutes to seal the porous layer on the surface of the stent, and then the calcium alginate hydrogel was freeze-dried and stored in a thermostat at 4 ℃ to obtain a sinus duct stent.

Further, taking the sinus tube stent formed in this embodiment with an inner diameter of 6mm as an example, the compression-rebound curves of the radial deformation rates of the sinus tube stents with wall thicknesses of 0.1mm, 0.3mm and 0.5mm reaching 50% were further analyzed, as shown in fig. 7, it can be seen that as the wall thickness of the stent increases, the supporting capacity increases, but the rebound rate after contraction decreases. Therefore, the sinus duct stent of the embodiment can achieve the purpose of balancing the support force and the rebound rate of the stent by designing the thickness of the stent during three-dimensional modeling. That is, the thickness of the design support, that is, the thickness of the 3D printing sheet, can be specifically set according to actual needs in the present embodiment.

As shown in fig. 4, in a second aspect of the present invention, a sinus duct support is provided, which is a cylindrical hollow support, and is prepared by the above-mentioned sinus duct support preparation method, and the specific preparation method refers to the above-mentioned description, and is not repeated herein.

This sinus pipe support possesses thermotropic shape memory deformability, can take place to correspondingly accomplish shrink and from the expansion action under the temperature stimulation, and based on this characteristics, this embodiment adopts thermotropic excitation recovery method to deploy the sinus pipe support, and concrete step includes:

and (2) carrying out gamma ray sterilization treatment on the obtained sinus stent, putting the sinus stent in a constant temperature water bath system at 40-45 ℃, enabling the diameter to be shrunk under a sinus stent pressing and holding tool, conveying the sinus stent to a collapsed nasal cavity through a sinus stent catheter, controlling the pressing and holding time in the water bath system within 30s, and then washing the sinus stent under heat flow at 35-40 ℃ for 8-12 s, thus finishing the deployment of the sinus stent.

The specific deployment method of the sinus duct support will be further described with reference to several specific examples:

example 5

The sinus tube stent obtained in example 1 described above was subjected to gamma ray sterilization treatment. After that, the sterilized sinus canal stent is placed in a constant temperature water bath system at 40 ℃, and the diameter is contracted under a stent crimping tool and is conveyed to the collapsed nasal cavity through a stent catheter, wherein the crimping time in the water bath system is controlled within 30s, and the sinus canal stent is flushed for 10s under the heat flow of 35 ℃, so that the deployment of the sinus canal stent in the example can be completed.

Example 6

The sinus tube stent obtained in example 2 described above was subjected to gamma ray sterilization treatment. After that, the sterilized sinus canal stent is placed in a constant temperature water bath system at 42 ℃, and the diameter is contracted under a stent crimping tool and is conveyed to the collapsed nasal cavity through a stent catheter, wherein the crimping time in the water bath system is controlled within 30s, and the sinus canal stent is flushed for 10s under the heat flow of 38 ℃, so that the deployment of the sinus canal stent in the example can be completed.

Example 7

The sinus tube stent obtained in example 3 described above was subjected to gamma ray sterilization treatment. After that, the sterilized sinus canal stent is placed in a constant temperature water bath system at 45 ℃ and is subjected to diameter shrinkage under a stent crimping tool and is conveyed to the collapsed nasal cavity through a stent catheter, wherein the crimping time in the water bath system is controlled within 30s, and the sinus canal stent is flushed for 10s under heat flow at 38 ℃, so that the deployment of the sinus canal stent in the example can be completed.

Example 8

The sinus tube stent obtained in example 4 described above was subjected to gamma ray sterilization treatment. After that, the sterilized sinus tube stent is placed in a constant temperature water bath system at 45 ℃, and is contracted in diameter under a stent crimping tool and is delivered to the collapsed nasal cavity through a stent catheter, wherein the time of crimping in the water bath system is controlled within 30s, and the sinus tube stent is rinsed for 10s under heat flow at 40 ℃, and then the deployment of the sinus tube stent in the example can be completed.

It should be noted that, in the present embodiment, the deployment of the sinus tube stent corresponds to the 4 embodiments described above, and it is obvious to those skilled in the art that the specific deployment may be performed according to actual situations, that is, the temperature and the time involved in the deployment of the sinus tube stent may be set according to actual situations, which is not limited in particular.

Compared with a traditional sacculus expansion support recovery system, the support thermotropic excitation recovery method adopted by the prepared paranasal sinus tube support makes full use of the shape memory recovery function of the support framework, greatly reduces the risk of mechanical scraping and even wall breaking caused by the sacculus to the nasal cavity when the support is mechanically expanded, creates a space for radial elastic expansion of the support due to the porous structure of the paranasal sinus tube support shell, and greatly reduces the probability of support displacement after the support is successfully deployed. In addition, after the drug on the surface of the sinus duct stent prepared by the embodiment is released, the completely degradable stent main body can be automatically degraded into fragments to enter a human body excretion system, the remains of the stent are taken out without a secondary operation, the biological safety is higher, the pain and the burden of a patient are reduced, and the stent implanted into the nasal cavity which is collapsed in the day can achieve the effect of gradually healing while the respiratory capacity of the patient is improved.

The invention provides a sinus duct stent and a preparation method thereof, and compared with the prior art, the sinus duct stent has the following beneficial effects: firstly, the invention adopts a 3D printing rapid forming technology, is not limited by the precision of a fused deposition type 3D printer instrument, ensures the consistency of forming conditions of each part of the bracket, so that the bracket has good elasticity, and the 3D printing prefabricated bracket side surface unfolding structure is combined with a hot gas welding technology, so that the brackets with different diameters and wall thickness ranges can be prepared to meet the requirements of different individual patients on the size, radial supporting force, elasticity and compliance of the bracket, and the radial supporting force and the rebound rate of the bracket can be adjusted through the wall thickness of the bracket. Secondly, the spiral reinforcing ribs formed on the bracket by utilizing the hot gas welding technology ensure the radial elasticity of the bracket, ensure that the bracket cannot be broken and lose efficacy early when being pressed by the nasal cavity wall, and effectively prevent the bracket part at the broken part from causing larger block falling off to cause the blockage of the original narrow nasal cavity again. Compared with the vertical reinforcing ribs, the spiral reinforcing ribs effectively disperse the compression and holding force applied to the periphery of the wall of the support, and the support with the spiral reinforcing ribs has the advantages that the maximum wall compression and the maximum deformation of the support are obviously reduced under the same stress condition compared with the support with the vertical reinforcing ribs. Thirdly, the invention adopts the annealing treatment to the thermoplastic polymer material to release the internal stress of the bracket caused during the curling, simultaneously improves the bonding strength of the welding seam, and simultaneously can increase the crystallinity of the polymer by controlling the annealing temperature and time parameters, so that the brittleness of the raw material is improved, and the bracket has good elasticity and meets the service requirement. And the porous drug-carrying layer is formed, so that the binding force between the drug and the stent is increased compared with a direct spraying method, the drug layer cannot fall off, the porous drug-carrying layer is subjected to hole sealing treatment by adopting calcium alginate hydrogel, the stent is effectively prevented from escaping from a matrix and subsequent burst release of the drug in the deployment process, the problem of insufficient drug-carrying capacity is avoided, and the probability of occurrence of medical accidents such as secondary blockage caused by the fact that the nasal cavity granulation tissue grows into the nasal cavity space is prevented. Compared with a balloon-expandable stent recovery system, the stent thermotropic excitation recovery method fully utilizes the shape memory recovery function of the stent framework, greatly reduces the risk of mechanical scraping and even wall breaking of the nasal cavity caused by the balloon during mechanical stent expansion, and greatly reduces the probability of stent displacement after the stent is successfully deployed because the porous structure of the sinus canal stent shell creates space for radial elastic expansion of the stent. Sixth, after the drug on the surface of the sinus duct stent is released, the completely degradable stent main body can be automatically degraded into fragments to enter a human body excretion system, the remains of the stent do not need to be taken out in a secondary operation, the pain and the burden of a patient are reduced, and the stent is implanted into a nasal cavity which is collapsed in nature, so that the respiratory capacity of the patient can be increased, and the effect of gradual healing can be achieved.

It will be understood that the above embodiments are merely exemplary embodiments taken to illustrate the principles of the present invention, which is not limited thereto. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit and substance of the invention, and these modifications and improvements are also considered to be within the scope of the invention.

Claims

1. A preparation method of a sinus duct stent is characterized by comprising the following specific steps:

coiling the thin slice around a preset reference shaft to form an annular structure, and after the thin slice is pre-fixed, carrying out heat treatment setting on the annular structure to obtain a hollow support;

forming a porous drug-carrying layer on a surface of the hollow stent, comprising: immersing the hollow stent into 80-120 mL of mixed solution of drug and chitosan, ultrasonically immersing for 0.5-1.5 h, and then carrying out freeze drying treatment to enable the chitosan to crust on the surface of the hollow stent to form the porous drug supporting layer;

2. The method for preparing a sinus canal stent according to claim 1, wherein the pre-fixing is followed by heat setting of the loop structure to obtain a hollow stent, comprising:

heat treatment setting is carried out on the annular structure at the temperature of 40-50 ℃ for 2-5 min, and a semi-finished hollow bracket is obtained;

3. The method for preparing a sinus duct support according to claim 2, wherein the preparing and forming of the reinforcing rib on the semi-finished hollow support to obtain the hollow support comprises:

4. The method for preparing a sinus tube stent according to claim 1, wherein the mixed solution of drug and chitosan comprises acetic acid at a concentration ranging from 1% (v/v) to 3% (v/v), chitosan at a viscosity ranging from 400 mPa-s to 600 mPa-s at a concentration ranging from 1% (w/v) to 3% (w/v), and sirolimus drug; wherein the content of the first and second substances,

5. The method for preparing a sinus tube support according to any one of claims 1 to 3, wherein the sealing the porous drug-carrying layer to obtain the sinus tube support comprises:

immersing the hollow stent with the porous drug supporting layer into 80-120 mL of saturated aqueous solution of sodium alginate, and dropwise adding 80-120 mL of CaCl into the saturated aqueous solution of sodium alginate ₂ Mechanically stirring the solution for 5-15 min to form calcium alginate hydrogel;

and sealing the porous drug supporting layer by using the calcium alginate hydrogel, and performing freeze drying treatment to obtain the sinus duct stent.

6. The method of preparing a sinus tube stent according to any one of claims 1 to 3, wherein the thermoplastic degradable polymer comprises at least one of polylactic acid, polycaprolactone, polyglycolic acid, polylactic-glycolic acid.

7. The method of preparing a sinus tube support according to any one of claims 1 to 3, wherein the sheet is a parallelogram-shaped sheet; wherein the content of the first and second substances,

the parallelogram thin slice is provided with any one of rhombus patterns, triangle patterns, trapezoid patterns and circular patterns which penetrate through the thickness of the parallelogram thin slice.

8. A method of preparing a sinus tube stent according to any one of claims 1 to 3, wherein the sheet has a length in the range of 10mm to 20mm, a width in the range of 20mm to 30mm, and a thickness in the range of 0.1mm to 0.5mm.

9. A sinus duct support prepared by the method of any one of claims 1 to 8.