CN114259607A - Preparation method of stent - Google Patents
Preparation method of stent Download PDFInfo
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- CN114259607A CN114259607A CN202111618653.2A CN202111618653A CN114259607A CN 114259607 A CN114259607 A CN 114259607A CN 202111618653 A CN202111618653 A CN 202111618653A CN 114259607 A CN114259607 A CN 114259607A
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- acid copolymer
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Abstract
A stent preparation method comprises preparing a stent by a first silk thread and a second silk thread, wherein the preparation of the second silk thread comprises the steps of preparing polylactic acid-glycolic acid copolymer-paclitaxel solution; preparing a polylactic acid-glycolic acid copolymer wire with a porous structure; and (3) immersing the porous polylactic acid-glycolic acid copolymer wire body into a polylactic acid-glycolic acid copolymer-paclitaxel solution to obtain the polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
Description
Technical Field
The invention belongs to the field of high molecular materials and biomedical devices, and particularly relates to a degradable polymer stent and a manufacturing method thereof.
Background
The body has various pipelines including blood vessels, digestive tracts, respiratory tracts, bile ducts, auditory canals and the like; blood vessels such as veins and arteries, blood vessels in the heart, and blood vessels in the neck; the digestive tract includes the esophagus, the intestine, etc. In the prior art, the pipeline is dredged by implanting the stent, and some stents can be used for therapy in the pipeline when supporting the pipeline.
Disclosure of Invention
The invention aims to provide a degradable stent.
A stent preparation method is characterized in that: the method comprises the following steps: preparing a first silk thread: preparing polydioxanone into a first filament; preparing a second silk thread: preparing polylactic acid-glycolic acid copolymer-paclitaxel solution; preparing a polylactic acid-glycolic acid copolymer wire with a porous structure; mixing the polylactic acid-glycolic acid copolymer with a salt particle to obtain a mixture of the polylactic acid-glycolic acid copolymer and the salt, and uniformly mixing the polylactic acid-glycolic acid copolymer and the salt mixture; extruding a polylactic acid-glycolic acid copolymer and the salt mixed filament, and repeatedly soaking the mixed filament in double distilled water to obtain a polylactic acid-glycolic acid copolymer filament body; immersing a polylactic acid-glycolic acid copolymer wire body into a polylactic acid-glycolic acid copolymer-paclitaxel solution to obtain a polylactic acid-glycolic acid copolymer-paclitaxel silk thread; and cleaning the surface of the polylactic acid-glycolic acid copolymer-paclitaxel silk thread to obtain a second silk thread.
Manufacturing a bracket: the first and second wires are fabricated into a stent.
Optionally, the stent manufacturing includes manufacturing a first wire as a first tube element and a second wire as a second tube element outside the first tube element.
Optionally, said manufacturing the first wire into the first pipe element comprises manufacturing the first wire of the first pipe element into a first helical line; the second wire of the second pipe element is also manufactured as a second helix; the helix angle direction of the first helix is opposite to the helix angle direction of the second helix.
Optionally, the second thread comprises polylactic acid-glycolic acid copolymer and paclitaxel, wherein the content of paclitaxel is 5.19x102 μ g/mm3-1.6x104 μ g/mm3, namely 5.19x102 μ g-1.6x104 μ g of paclitaxel is contained in the polylactic acid-glycolic acid copolymer and paclitaxel thread material per cubic millimeter.
Optionally, extruding the polylactic acid-glycolic acid copolymer and the salt mixed filament, and repeatedly soaking the mixed filament in double distilled water until the salt is dissolved in the double distilled water to obtain the polylactic acid-glycolic acid copolymer filament body.
Optionally, the first tube element is provided at an end of the stent; the second pipe element is arranged in the middle of the bracket; the tensile strength of the first silk thread is 300-500MPa, and the diameter of the first silk thread is 0.1-0.5 mm; the second degradable tensile strength is 40-100MPa, and the diameter of the first silk thread is 0.1-0.5 mm.
Optionally, the salt is sodium chloride, the polylactic acid-glycolic acid copolymer and one type of sodium chloride particle are mixed to obtain a mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride, and the polylactic acid-glycolic acid copolymer and the sodium chloride mixture are uniformly mixed, wherein the step of uniformly mixing the polylactic acid-glycolic acid copolymer and the sodium chloride mixture comprises the step of stirring the polylactic acid-glycolic acid copolymer and the sodium chloride mixture in a low-speed stirrer at 25 ℃ for 1 hour at a speed of 60r/min to uniformly mix the particles; and then placing the mixed filament material into an extruder, extruding the mixed filament material of the polylactic acid-glycolic acid copolymer and the sodium chloride with the diameter of 0.1-0.5mm at the temperature of 180 ℃ and under the pressure of 5-7MPa, repeatedly soaking the mixed filament material in double distilled water, and obtaining a porous polylactic acid-glycolic acid copolymer filament material body after completely removing the sodium chloride, wherein the porous polylactic acid-glycolic acid copolymer filament material body is dried under the reduced pressure condition to constant weight.
Optionally, the first tube element is provided at an end of the stent; the second pipe element is arranged in the middle of the bracket; the tensile strength of the first silk thread is 300-500MPa, and the diameter of the first silk thread is 0.1-0.5 mm; the second degradable tensile strength is 40-100MPa, and the diameter of the first silk thread is 0.1-0.5 mm.
Optionally, a third pipe element is manufactured at one end of the stent, a fourth pipe element is manufactured at the other end of the stent, the materials of the third pipe element and the fourth pipe element comprise degradable metals, and the degradable metals comprise magnesium-aluminum alloy, magnesium-manganese alloy, magnesium-zinc alloy, magnesium-rare earth and gold, magnesium-lithium and gold, magnesium-calcium alloy and magnesium-silver alloy; the manufacturing a stent linking portion that links the third pipe element and the fourth pipe element.
Optionally, before the polylactic acid-glycolic acid copolymer and a sodium chloride particle are mixed to obtain a mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride, a material of the polylactic acid-glycolic acid copolymer with the particle size range of 200-250 μm is selected and sieved out, and then the sodium chloride particles with the same particle size range as the polylactic acid-glycolic acid copolymer are mixed according to the mass ratio of 1 (16-20) to obtain the mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride.
Optionally, the method further comprises a freeze-drying step, in which the polylactic acid-glycolic acid copolymer wire body with the porous structure is immersed in a polylactic acid-glycolic acid copolymer-paclitaxel stock solution for freeze-drying treatment, so as to obtain the porous polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
Optionally, after the polylactic acid-glycolic acid copolymer wire with a porous structure is immersed in the polylactic acid-glycolic acid copolymer-paclitaxel stock solution, a 2.5% mannitol aqueous solution is added, and the mixed solution is freeze-dried to obtain the polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
Optionally, the manufacturing of the stent comprises the following steps: preparing polylactic acid-glycolic acid copolymer-paclitaxel solution; preparing a polylactic acid-glycolic acid copolymer wire with a porous structure; mixing the polylactic acid-glycolic acid copolymer with NaCl particles to obtain a mixture of the polylactic acid-glycolic acid copolymer and sodium chloride, and uniformly mixing the polylactic acid-glycolic acid copolymer and the sodium chloride mixture; extruding a polylactic acid-glycolic acid copolymer and sodium chloride mixed wire, and repeatedly soaking the mixed wire in double distilled water to obtain a polylactic acid-glycolic acid copolymer wire body; immersing a polylactic acid-glycolic acid copolymer wire body into a polylactic acid-glycolic acid copolymer-paclitaxel solution to obtain a polylactic acid-glycolic acid copolymer-paclitaxel silk thread; cleaning the surface of polylactic acid-glycolic acid copolymer-paclitaxel silk thread, and coiling; the polylactic acid-glycolic acid copolymer-paclitaxel silk thread and the polydioxanone silk thread are subjected to weaving, 3D printing and other methods to prepare the stent.
Drawings
FIG. 1 Stent Panels of one embodiment of the stents of the present disclosure
FIG. 2 is a schematic cross-sectional view of one embodiment of the present disclosure
FIG. 3 enlarged view at A of a stent floor plan of one embodiment of the present disclosure
FIG. 4 deformation view of a stent according to one embodiment of the present disclosure
FIG. 5A cross-sectional view of a second filament according to one embodiment of the present disclosure
FIG. 6 axial view of a second filament of one embodiment of the present disclosure
FIG. 7 one embodiment of the present disclosure
FIG. 8 an enlarged view of the stent of FIG. 7 of the present disclosure at B
FIG. 9 one embodiment of a stent of the present disclosure
FIG. 10 one embodiment of the present disclosure
Detailed Description
The body has various pipelines including blood vessels, digestive tracts, respiratory tracts, bile ducts, auditory canals and the like; the blood vessels comprise veins, arteries, blood vessels of heart parts, neck blood vessels and the like; the digestive tract includes the esophagus, the intestine, etc. In the prior art, the pipeline is dredged by implanting the stent, and some stents can be used for therapy in the pipeline when supporting the pipeline.
The alimentary tract includes the esophagus. Clinically, esophageal stenosis is a common symptom of digestive system diseases, and comprises two forms of benign esophageal stenosis (for example, stenosis after chemical erosive burn, congenital stenosis of esophagus and the like) and local tissue hyperplasia of esophagus caused by malignant esophageal cancer. Esophageal stenosis can cause esophageal obstruction in patients, leading to dysphagia and even respiratory failure. The esophageal stent implantation can provide enough physical support for the part which is narrowed due to the pathological changes, and keep the cavity channel smooth so as to smoothly enter water and eat food.
In the prior art, when the irregular shape of the inner wall lesion is adaptively set, the following method is mostly adopted. For example, in the first mode, the larger meshes are adopted, and can accommodate the lesion part, so that the stress of the stent on the inner wall is reduced. Although this method can reduce the stress on the inner wall by the stent, the larger mesh arrangement makes the lesion on the inner wall easily penetrate through the mesh, thereby stimulating the proliferation of the lesion.
In order to prevent the pathological hyperplasia, electrostatic spinning technology or drug coating technology is also commonly adopted in the field, and a drug coating is arranged on the outer side of the stent. Obviously, the coating can be arranged to inhibit the hyperplasia of the lesion by using the medicament in the coating, but the double-layer stent has the advantages of more complex and higher cost in manufacturing. The inner layer of such stents is typically made of a metallic material to provide the supporting force. The degradation period of the metal stent is different from that of the outer drug coating, so that the design of the stent is more difficult.
The second method comprises the following steps: when the support is woven, fixing points of the support silk threads are arranged at intervals, and the support can adapt to the irregular pressure of the inner wall to the inner side at the position where the support silk threads are not connected, so that the protruding stress of the support to the inner wall is reduced. However, this weaving method is complicated and the manufacturing cost is high. Moreover, the stent manufactured by the weaving method has uneven point transition of the stent supporting force, too small supporting force at the position where the wires are not connected and too large supporting force at the position where the wires are connected.
Accordingly, the present disclosure provides a stent that overcomes the deficiencies in the prior art.
The first embodiment is as follows:
as shown in fig. 1, the present disclosure discloses a stent 10 that may be used to support a body lumen such as an esophagus, a blood vessel, an airway, an ear canal, or the like. The stent is composed of a plurality of tube elements, each of which is formed by bending a wire, the plurality of tube elements constituting, in combination with each other, a hollow tube capable of allowing a fluid to flow from one end to the other end; the fluid may be blood, or food flowing in the esophagus or food being digested, or air flowing in the hollow tube. Fig. 1 shows a schematic view of the stent 10 deployed flat. The plurality of pipe elements comprises a first pipe element comprising at least a first filament 1(101, 102, 103), the first filament comprising a first degradable material; the plurality of pipe elements further comprises a second pipe element comprising at least a second filament 2(201, 202, 203), the second filament comprising a second degradable material; and the stent is manufactured by the methods of weaving the first silk thread and the second silk thread, 3D printing and the like.
As shown in FIG. 4, the first pipe element has a first diameter D1 and the second pipe element has a diameter D2, and the first diameter D1 of the first pipe element compresses to a first compressed diameter D12 and the first diameter D2 of the second pipe element compresses to a second compressed diameter D22 when subjected to the same radial compressive force F. For the first pipe element, the diametric compressed dimension is 2S 1; for the second pipe element, the compression size is 2S 2.
A first deformation ratio λ 1 of the first pipe element of 2S 1/D1;
a second deformation ratio λ 2 of the second pipe element is 2S 2/D2;
wherein the first deformation ratio λ 1 is different from the second deformation ratio λ 2.
Alternatively, D1 is the same as D2, or D1 is slightly smaller in diameter than D2.
Advantageously, the first tube member provides greater support than the second tube when the first tube member has a lower deformation rate than the second tube member, i.e., when the stent is compressed when the stent is implanted in a body lumen. The inner walls of blood vessels and esophagus have irregular shapes and different flexibilities due to pathological changes. Due to the adoption of materials with different supporting forces, the support has slow transition supporting force change while having supporting force in the circumferential direction and the axial direction, and the hard support is prevented from puncturing the pathological changes of the inner wall. I.e. the wires 101, 102, 103 of the pipe element 1 are able to provide a greater supporting force; the wires 201, 202, 203 of the tube element provide a certain flexibility. The two silk threads with different supporting forces are woven together to form the stent, and the interweaving points of the two silk threads are uniformly distributed, so that the mechanical property of the stent is more stable and predictable.
Optionally, the ratio of the deformation ratio λ 1 of the first pipe element diameter D1 to the deformation ratio λ 2 of the second pipe element diameter D2 ranges from 0.7< λ 1: λ 2< 0.9. Within this range of deformation ratios, the overall performance of the stent is optimized, i.e. both a greater support force of the first tube element can be exerted and the flexibility of the second tube element can be fully utilized. The first pipe element has a compressibility less than the second pipe element and a tensile strength greater than the tensile strength of the second pipe element.
Beneficially, disclosed herein is a single layer stent, simple to manufacture; and the materials adopted by the stent are all polymer materials and do not contain metal materials, so that the control of the degradation period of the stent is easier.
Alternatively, for example, as shown in fig. 2, the first tube element is disposed on the inside of the stent and the second tube element is disposed on the outside of the stent. When the bracket is subjected to the pressure of the lumen, the second pipe element transmits the pressure to the first pipe element, so that the deformation of the whole bracket is more uniform. As shown in fig. 3, the wires L1 and L4 of the first pipe element enclose a quadrilateral with the wires L2 and L3 of the second pipe element and form four vertices, D1, D2, D3, D4. Four vertex uniform sections. The pressure of the cavity to the second wire is evenly transmitted to the first wire. As shown in FIG. 4, the second wire of the second tube element, when subjected to luminal pressure, is capable of forming a diameter D22 that fits inside the diameter of the first tube element, the second tube element forming a virtual diameter D12 that is less than the diameter D12 of the first tube element after compression.
Advantageously, in the stent manufactured by weaving or 3D printing or other methods in the present disclosure, the connection points or force bearing points between the threads are evenly distributed, so that the stent support force changes more softly.
Example two:
the first degradable material comprises: one or more of polycaprolactone, polyanhydride, tyrosine polycarbonate, polyglycolide-lactide, and polydioxanone. The degradable material has higher hardness and can provide larger supporting force.
Optionally, the tensile strength of the first degradable material is 300-500 MPa.
Optionally, the first degradable material is polydioxanone, and the tensile strength is 440-.
The second degradable material comprises: polylactic acid-glycolic acid copolymer, polylactic acid, polyglycolic acid, and copolymers of polylactic acid and polyglycolic acid. The material is relatively low in hardness and can provide flexibility for the stent to accommodate and bear the protruding parts of the lesions of the inner wall.
Optionally, the tensile strength of the first degradable material is 40-100 MPa.
Optionally, the first degradable material is polylactic acid and polyglycolic acid, and the tensile strength is 45-90 MPa.
Advantageously, the two polymer materials are used simultaneously, so that the controlled degradation time is guaranteed. A self-expanding polymeric material.
Example three:
as shown in fig. 5 and 6, the second degradable material includes one or more of the following materials: polylactic acid-glycolic acid copolymer, polylactic acid, polyglycolic acid, and copolymers of polylactic acid and polyglycolic acid. The second filament 2 comprises a second filament body 2110 with a plurality of recesses in which drug particles 2111 are embedded.
Optionally, the second thread further comprises one or more of paclitaxel, paclitaxel derivatives, taxane, taxol, docetaxel, epothilone, nocodazole, cabazitaxel, combretastatin, docetaxel trihydrate, vinorelbine tartrate, combretastatin disodium phosphate, albendazole, triclabendazole, vinflunine tartrate, rapamycin, and rapamycin derivatives.
Advantageously, by incorporating a drug, such as paclitaxel, into the polylactic acid-glycolic acid copolymer, the stent itself is provided with the drug, which reduces the process flow compared to stent graft.
Meanwhile, the polylactic acid-glycolic acid copolymer and the paclitaxel are mixed and processed into the silk thread, the diameter of the silk thread is uniform, and the dosage of the paclitaxel contained in the silk thread is also uniform, so that the dosage of the paclitaxel in the stent can be calculated only by measuring how many silk threads are used when the stent is processed. However, the process method of adding paclitaxel to the stent in a film covering manner has the disadvantages that the film covering technology is not uniform and the film covering thickness is not consistent due to immaturity of the film covering technology. The dosage inaccuracy is calculated by measuring the thickness of the coating film. Therefore, the scheme disclosed by the invention can be used for calculating the medicine carrying quantity more accurately and conveniently.
Example four:
the second thread comprises polylactic acid-glycolic acid copolymer and paclitaxel, wherein the content of the paclitaxel is 5.19x102μg/mm3-1.6x104μg/mm3。
The beneficial results are: the proportion of paclitaxel can be adjusted. Due to the fact that the proportion of the paclitaxel is different, the diameter of the second silk thread can be adjusted according to the proportion of the paclitaxel, and under the condition that the amount of the paclitaxel is large, the size of the second silk thread is increased, and therefore the degradation period is prolonged.
Example five:
the diameter of the first wire is: 0.1-0.5 mm;
the diameter of the second wire is: 0.1-0.5 mm.
Alternative a):
the first degradable material of the first filament comprises polydioxanone, with a tensile strength of 440 MPa;
the second degradable material of the second thread comprises a copolymer of polylactic acid and polyglycolic acid, having a tensile strength of 45 MPa.
The diameter of the first wire is 0.1 mm; the diameter of the second wire is 0.3 mm;
alternative b):
the first degradable material of the first filament comprises polydioxanone, having a tensile strength of 450 MPa;
the second degradable material of the second filament comprises a copolymer of polylactic acid and polyglycolic acid, having a tensile strength of 40 MPa.
The diameter of the first wire is 0.2 mm; the diameter of the second wire is 0.2 mm;
alternative c):
the first degradable material of the first filament comprises polydioxanone, with a tensile strength of 480 MPa;
the second degradable material of the second thread comprises a copolymer of polylactic acid and polyglycolic acid, having a tensile strength of 45 MPa.
The diameter of the first wire is 0.3 mm; the diameter of the second wire is 0.5 mm;
advantageously, in the case where greater support is required, the diameter of the first wire can be chosen to be larger; where a softer stent is desired, the diameter of the second wire may be selected to be smaller; meanwhile, the size of the supporting force can be realized by adjusting the weaving density of the first silk threads and the weaving density of the second silk threads.
Example six:
the first and second wires have contact points through which the first and second wires are connected.
Advantageously, the two wires are connected by contact points, making the stent one piece. The rigidity and flexibility of the stent have continuity, and the stress of the stent when the stent is implanted into a cavity is reduced.
Example seven:
the contact point further comprises a connecting element, which is made of a degradable material.
And (4) point bonding the liquid at the contact point. The two silk threads can be connected and fixed through the bonding liquid by adopting methods such as ultraviolet curing and the like.
Advantageously, the connection of the tube elements of the stent is made stronger by the connecting elements.
Example eight:
as shown in fig. 1, the first tube element includes a plurality of first threads, the second tube element includes a plurality of second threads, in a tiled view of the stent, the first threads are parallel to each other, the second threads are parallel to each other, two adjacent first threads intersect with each other to form a quadrangle, and four vertexes of the quadrangle are formed by the intersection of the first threads and the second threads. As shown in fig. 2, in a radial cross-sectional view of the stent, the first wires are disposed on one side close to the central line of the stent shaft, and the second wires are disposed on the other side far from the central line of the stent shaft. The stent is manufactured by 3D printing, i.e. first printing a first thread to form a first tube element and then printing a second thread to form a second tube element, or weaving, first weaving a first thread to form a first tube element and then weaving a second thread to form a second tube element.
Advantageously, the first wire has a high tensile strength and the second wire has a low tensile strength, and placement of the first wire inside the stent may provide better support for the lumen with greater tensile strength of the first tubular element. And the first wire and the second wire form an intersection point, and when the second wire is bent inwards due to the pressure of the lumen, the second wire transmits the received pressure to the first wire through the intersection point.
The first tube element comprises a number of first filaments and the second tube element comprises a number of second filaments, and the number of first filaments is different from the number of second filaments. When the support force required by the stent is higher, the ratio of the first wire to the second wire is 1: 1; when the stent is required to be softer, the number of the second wires is more than that of the first wires, for example, the ratio of the first wires to the second wires is 1:2, namely, one first wire is clamped between two second wires; it is also possible to choose the ratio of the first and second threads to be 1:5, i.e. two second threads on either side of the first thread.
The beneficial results are: the supporting force softness of the bracket is adjusted by adjusting the proportion of the silk threads.
Example nine:
the connecting portion further includes a magnesium alloy. The magnesium alloy can be selected from magnesium-aluminum alloy, magnesium-manganese alloy, magnesium-zinc alloy, magnesium rare earth and gold, magnesium lithium and gold, magnesium-calcium alloy and magnesium-silver alloy, and the connecting part material of magnesium-lithium alloy, gold, magnesium-calcium alloy and magnesium-silver alloy can be magnesium alloy besides degradable high polymer material. The bracket can be scanned by scanning equipment in the bracket implantation process or after the bracket is implanted, so that the magnesium-aluminum alloy is identified, and the bracket is positioned.
Example ten:
as shown in fig. 10, the stent 61 is composed of a first wire 601 and a second wire 602, and further includes a third pipe element 62 and a fourth pipe element 63, the material of which each includes a magnesium alloy. The third pipe element and the fourth pipe element are respectively arranged at one end of the stent, and the length and the position information of the stent can be identified through scanning equipment during or after the stent is implanted.
The bracket also includes a connecting portion 64. Connecting portion 64 is connected to third and fourth pipe elements 62, 62 and connecting portion 64 is connected to the first and second wires.
Advantageously, the bends in the third and fourth tube elements may enable a relatively good compression of the stent; since the third and fourth pipe elements are composed of a magnesium alloy having a larger supporting force, a larger supporting force can be provided.
Example eleven:
as shown in fig. 7 and 8, the stent 41 includes first pipe elements 402, 403 and a second pipe element 401. The first tube element is braided from first filaments 4021, 4031; the second tube element is woven from second filaments 4011. The first tube element is located at an end of the stent and the second tube element is located in a middle of the stent.
Advantageously, the first wires with higher strength are adopted at the two ends, so that the bracket provides larger supporting force during positioning in the pipeline.
Optionally, as shown in fig. 8, the first filaments 4021 are integrally woven with the second filaments 4011 by weaving.
The advantages are that the connection is uniformly realized in a weaving mode, and the integrity is more complete.
Example twelve:
as shown in fig. 9, embodiment twelve is an alternative to embodiment eleven. Wherein the first pipe element opening is in an expanded configuration. Advantageously, the arrangement enables better retention of the stent at both ends within the duct.
The processing technology of the bracket comprises the following steps:
1. preformed polylactic acid-glycolic acid copolymer-paclitaxel solution
101: preparing an emulsion: adding 100mg of polylactic acid-glycolic acid copolymer into 2.0ml of dichloromethane solution to prepare emulsion solution;
102: paclitaxel solution: adding paclitaxel, dissolving with dichloromethane solution of polylactic acid-glycolic acid copolymer, and ultrasonic processing for 3-5 min;
103: preparing a polyvinyl alcohol solution: the paclitaxel solution was added dropwise to 30ml of an aqueous polyvinyl alcohol (PVA) solution, stirred at high speed, and then diluted with water until the PVA concentration was 2%. Stirring the polyvinyl alcohol solution at a low speed of 500r/min for 2 hours;
104: preparing polylactic acid-glycolic acid copolymer-paclitaxel stock solution: treating the prepared polyvinyl alcohol solution, filtering out an external water phase in the polylactic acid-glycolic acid copolymer-paclitaxel solution, and repeatedly centrifuging and washing the residual solution. Until the polylactic acid-glycolic acid copolymer-paclitaxel stock solution does not contain dichloromethane and PVA, and the polylactic acid-glycolic acid copolymer-paclitaxel stock solution is obtained for standby.
2. Preparing a polylactic acid-glycolic acid copolymer wire with a highly porous structure:
the parameters are: 5L/95G, 10L/90G, 15L/85G, 20L/80G, 25L/75G, 30L/70G, 35L/65G, 40L/60G, 45L/55G, 50L/50G, 55L/45G, 60L/40G, 65L/35G, 70L/30G, 75L/25G, 80L/20G, 85L/15G, 90L/10G and 95L/5G, and screening out polylactic acid-glycolic acid copolymer materials with the particle size range of 200-250 mu m, and then mixing NaCl particles with the same particle size range as the materials according to the mass ratio of 1 (16-20) to obtain a polylactic acid-glycolic acid copolymer and sodium chloride mixture. The mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride is stirred for 1 hour at the temperature of 25 ℃ in a low-speed stirrer at the speed of 60r/min, so that the particles are uniformly mixed. And then placing the mixed filament material into an extruder, extruding the mixed filament material of the polylactic acid-glycolic acid copolymer and the sodium chloride with the diameter of 0.1-0.5mm at the temperature of 180 ℃ and under the pressure of 5-7MPa, repeatedly soaking the mixed filament material in double distilled water, and obtaining a highly porous polylactic acid-glycolic acid copolymer filament material body after completely removing NaCl, wherein the polylactic acid-glycolic acid copolymer filament material body is dried to constant weight under the condition of reduced pressure for later use.
A freeze-drying procedure: and (3) immersing the polylactic acid-glycolic acid copolymer wire body with a highly porous structure into a polylactic acid-glycolic acid copolymer-paclitaxel stock solution, and performing freeze-drying treatment to obtain the polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
Alternatively, the highly porous structured polylactic acid-glycolic acid copolymer is weighed and the weight W1 is recorded. And (3) immersing the polylactic acid-glycolic acid copolymer wire with a highly porous structure into a polylactic acid-glycolic acid copolymer-paclitaxel stock solution, and recording the weight W2 of the polylactic acid-glycolic acid copolymer wire after freeze-drying treatment. The weight difference before and after lyophilization, i.e., W-W2-W1, is the weight of the polylactic acid-glycolic acid copolymer-paclitaxel stock solution embedded in the polylactic acid-glycolic acid copolymer filament. The amount of the paclitaxel carried in the polylactic acid-glycolic acid copolymer silk can be calculated according to the amount of the paclitaxel contained in the polylactic acid-glycolic acid copolymer-paclitaxel stock solution.
Optionally, after the polylactic acid-glycolic acid copolymer wire with a highly porous structure is immersed in the polylactic acid-glycolic acid copolymer-paclitaxel stock solution, a 2.5% mannitol aqueous solution is added, and the mixed solution is freeze-dried. To obtain the polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
Advantageously, mannitol is a lyoprotectant, maintaining the drug-loaded stability of the loaded microspheres, which may be present in the wire.
Optionally, the paclitaxel content is 5.19x102μg/mm3-1.6x104μg/mm3That is, the polylactic acid-glycolic acid copolymer and the paclitaxel silk material contain paclitaxel 5.19x10 per cubic millimeter2μg-1.6x104μg。
The polylactic acid-glycolic acid copolymer-paclitaxel silk thread is subjected to surface cleaning and is formed into a dish.
4. Preparing a bracket:
the polylactic acid-glycolic acid copolymer-paclitaxel silk thread and the polydioxanone silk thread are prepared into the stent by methods of weaving, 3D printing and the like.
Optionally, the manufacturing of the stent includes manufacturing a first wire as a first tube element and a second wire as a second tube element outside the first tube element; said forming the first wire into a first tube element includes forming the first wire of the first tube element into a first helical line; the second wire of the second pipe element is also manufactured as a second helix; the helix angle direction of the first helix is opposite to the helix angle direction of the second helix.
Although the present invention has been described with respect to the preferred embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A stent preparation method is characterized in that: the method comprises the following steps:
preparing a first silk thread: preparing polydioxanone into a first filament;
preparing a second silk thread: preparing polylactic acid-glycolic acid copolymer-paclitaxel solution;
preparing a polylactic acid-glycolic acid copolymer wire with a porous structure;
mixing the polylactic acid-glycolic acid copolymer with a salt particle to obtain a mixture of the polylactic acid-glycolic acid copolymer and the salt, and uniformly mixing the polylactic acid-glycolic acid copolymer and the salt mixture; extruding a polylactic acid-glycolic acid copolymer and the salt mixed filament, and repeatedly soaking the mixed filament in double distilled water to obtain a porous polylactic acid-glycolic acid copolymer filament body;
immersing a porous polylactic acid-glycolic acid copolymer wire body into a polylactic acid-glycolic acid copolymer-paclitaxel solution to obtain a polylactic acid-glycolic acid copolymer-paclitaxel silk thread;
and cleaning the surface of the polylactic acid-glycolic acid copolymer-paclitaxel silk thread to obtain a second silk thread.
Manufacturing a bracket:
the first and second wires are fabricated into a stent.
2. A method of preparing a stent according to claim 1, wherein: the stent fabrication includes fabricating a first wire as a first tube element and fabricating a second wire as a second tube element outside the first tube element.
3. A method of preparing a stent according to claim 2, wherein: said forming the first wire into a first tube element includes forming the first wire of the first tube element into a first helical line;
the second wire of the second pipe element is also manufactured as a second helix;
the helix angle direction of the first helix is opposite to the helix angle direction of the second helix.
4. A method of preparing a stent according to claim 3, wherein: the second silk thread comprises polylactic acid-glycolic acid copolymer and paclitaxel, wherein the content of the paclitaxel is 5.19x102 mu g/mm3-1.6x104 mu g/mm3, namely, the content of the paclitaxel in each cubic millimeter of the polylactic acid-glycolic acid copolymer and the paclitaxel silk thread material is 5.19x102 mu g-1.6x104 mu g.
5. A method of preparing a stent according to claim 4, wherein:
the salt is sodium chloride, and the salt is sodium chloride,
mixing the polylactic acid-glycolic acid copolymer with sodium chloride particles to obtain a mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride, and uniformly mixing the polylactic acid-glycolic acid copolymer with the sodium chloride mixture, wherein the step of uniformly mixing the polylactic acid-glycolic acid copolymer with the sodium chloride mixture comprises the step of stirring the polylactic acid-glycolic acid copolymer and the sodium chloride mixture in a low-speed stirrer at 25 ℃ for 1 hour at a speed of 60r/min to uniformly mix the particles;
and then placing the mixed filament material into an extruder, extruding the mixed filament material of the polylactic acid-glycolic acid copolymer and the sodium chloride with the diameter of 0.1-0.5mm at the temperature of 180 ℃ and under the pressure of 5-7MPa, repeatedly soaking the mixed filament material in double distilled water, and obtaining a porous polylactic acid-glycolic acid copolymer filament material body after completely removing the sodium chloride, wherein the porous polylactic acid-glycolic acid copolymer filament material body is dried under the reduced pressure condition to constant weight.
6. A method of preparing a stent according to claim 5, wherein: the first pipe element is arranged at the end part of the bracket; the second pipe element is arranged in the middle of the bracket;
the tensile strength of the first silk thread is 300-500MPa, and the diameter of the first silk thread is 0.1-0.5 mm;
the second degradable tensile strength is 40-100MPa, and the diameter of the first silk thread is 0.1-0.5 mm.
7. A method of making a stent according to claim 3, wherein a third tube element is fabricated at one end of said stent and a fourth tube element is fabricated at the other end of said stent, said third and fourth tube elements being made of a material comprising a degradable metal selected from the group consisting of magnesium-aluminum alloy, magnesium-manganese alloy, magnesium-zinc alloy, magnesium-rare earth and gold, magnesium-lithium and gold, magnesium-calcium alloy, magnesium-silver alloy;
the manufacturing a stent linking portion that links the third pipe element and the fourth pipe element.
8. A method of preparing a stent according to claim 6 or 7, wherein: before mixing the polylactic acid-glycolic acid copolymer with a sodium chloride particle to obtain the mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride, selecting a material of the polylactic acid-glycolic acid copolymer with the particle size range of 200-250 mu m, screening out, and then mixing the sodium chloride particles with the same particle size range as the polylactic acid-glycolic acid copolymer according to the mass ratio of 1 (16-20) to obtain the mixture of the polylactic acid-glycolic acid copolymer and the sodium chloride.
9. A method of preparing a stent according to claim 8, wherein: the method may further comprise a step of lyophilisation,
and (3) immersing the polylactic acid-glycolic acid copolymer wire body with the porous structure into a polylactic acid-glycolic acid copolymer-paclitaxel stock solution, and performing freeze-drying treatment to obtain the porous polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
10. The method of preparing a stent of claim 9, wherein: immersing the polylactic acid-glycolic acid copolymer wire with a porous structure into polylactic acid-glycolic acid copolymer-paclitaxel stock solution, adding 2.5% mannitol aqueous solution, and freeze-drying the mixed solution to obtain the polylactic acid-glycolic acid copolymer-paclitaxel silk thread.
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Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1363399A (en) * | 2002-01-29 | 2002-08-14 | 清华大学 | Process for preparing internally degradable tubular liver tissue frame material |
| CN1367023A (en) * | 2002-03-08 | 2002-09-04 | 清华大学 | Preparation method of biodegradable medicine composite macromolecular scaffold material |
| US20030113359A1 (en) * | 2001-01-16 | 2003-06-19 | Vascular Therapies, Llc | Apparatus and methods for preventing or treating failure of hemodialysis vascular access and other vascular grafts |
| US20040026811A1 (en) * | 2002-01-02 | 2004-02-12 | The Regents Of The University Of Michigan | Tissue engineering scaffolds |
| CN101781815A (en) * | 2010-02-03 | 2010-07-21 | 东华大学 | Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold |
| US20100256746A1 (en) * | 2009-03-23 | 2010-10-07 | Micell Technologies, Inc. | Biodegradable polymers |
| CN102908216A (en) * | 2012-10-30 | 2013-02-06 | 东南大学 | Biodegradable medical human body cavity channel inner bracket and preparation method thereof |
| CN103169522A (en) * | 2006-05-24 | 2013-06-26 | 泰科保健集团有限合伙公司 | Flexible vascular occluding device |
| CN105055312A (en) * | 2015-09-07 | 2015-11-18 | 苏州纳诺康生物技术有限公司 | Method for preparing docetaxel drug-loaded nanoparticles with polylactic acid/hydroxyglycollic acid copolymer as material |
| CN105670249A (en) * | 2016-01-25 | 2016-06-15 | 中国科学院长春应用化学研究所 | Polylactic acid porous material and preparation method thereof |
| CN107029302A (en) * | 2016-02-01 | 2017-08-11 | 黑龙江鑫达企业集团有限公司 | The PLA/PCL composite material human bodies support of pipelines of controllable safety and its preparation |
| CN107206122A (en) * | 2015-02-13 | 2017-09-26 | W.L.戈尔及同仁股份有限公司 | Coherent simple layer high intensity synthetic polymer composite for artificial valve |
| CN107320224A (en) * | 2017-06-09 | 2017-11-07 | 东华大学 | Weaving base reinforcing degradable intraluminal stent and its preparation and application |
| CN108066048A (en) * | 2017-12-20 | 2018-05-25 | 东华大学 | It is thermally bonded degradable intraluminal stent of composite construction and its preparation method and application |
| US20200253760A1 (en) * | 2017-12-07 | 2020-08-13 | Ooo "Ik Sovremennye Tekhnologii" | Biodegradable intravascular shape memory stent |
| CN112312936A (en) * | 2018-03-12 | 2021-02-02 | 流体生物科技有限公司 | Bioabsorbable guide stent |
| CN113301860A (en) * | 2019-01-18 | 2021-08-24 | W.L.戈尔及同仁股份有限公司 | Bioabsorbable medical device |
-
2021
- 2021-12-28 CN CN202111618653.2A patent/CN114259607B/en active Active
Patent Citations (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030113359A1 (en) * | 2001-01-16 | 2003-06-19 | Vascular Therapies, Llc | Apparatus and methods for preventing or treating failure of hemodialysis vascular access and other vascular grafts |
| US20040026811A1 (en) * | 2002-01-02 | 2004-02-12 | The Regents Of The University Of Michigan | Tissue engineering scaffolds |
| CN1363399A (en) * | 2002-01-29 | 2002-08-14 | 清华大学 | Process for preparing internally degradable tubular liver tissue frame material |
| CN1367023A (en) * | 2002-03-08 | 2002-09-04 | 清华大学 | Preparation method of biodegradable medicine composite macromolecular scaffold material |
| CN103169522A (en) * | 2006-05-24 | 2013-06-26 | 泰科保健集团有限合伙公司 | Flexible vascular occluding device |
| US20100256746A1 (en) * | 2009-03-23 | 2010-10-07 | Micell Technologies, Inc. | Biodegradable polymers |
| CN101781815A (en) * | 2010-02-03 | 2010-07-21 | 东华大学 | Preparation method of porous fiber with controllable degradation rate for tissue engineering scaffold |
| CN102908216A (en) * | 2012-10-30 | 2013-02-06 | 东南大学 | Biodegradable medical human body cavity channel inner bracket and preparation method thereof |
| CN107206122A (en) * | 2015-02-13 | 2017-09-26 | W.L.戈尔及同仁股份有限公司 | Coherent simple layer high intensity synthetic polymer composite for artificial valve |
| CN105055312A (en) * | 2015-09-07 | 2015-11-18 | 苏州纳诺康生物技术有限公司 | Method for preparing docetaxel drug-loaded nanoparticles with polylactic acid/hydroxyglycollic acid copolymer as material |
| CN105670249A (en) * | 2016-01-25 | 2016-06-15 | 中国科学院长春应用化学研究所 | Polylactic acid porous material and preparation method thereof |
| CN107029302A (en) * | 2016-02-01 | 2017-08-11 | 黑龙江鑫达企业集团有限公司 | The PLA/PCL composite material human bodies support of pipelines of controllable safety and its preparation |
| CN107320224A (en) * | 2017-06-09 | 2017-11-07 | 东华大学 | Weaving base reinforcing degradable intraluminal stent and its preparation and application |
| US20200253760A1 (en) * | 2017-12-07 | 2020-08-13 | Ooo "Ik Sovremennye Tekhnologii" | Biodegradable intravascular shape memory stent |
| CN108066048A (en) * | 2017-12-20 | 2018-05-25 | 东华大学 | It is thermally bonded degradable intraluminal stent of composite construction and its preparation method and application |
| CN112312936A (en) * | 2018-03-12 | 2021-02-02 | 流体生物科技有限公司 | Bioabsorbable guide stent |
| CN113301860A (en) * | 2019-01-18 | 2021-08-24 | W.L.戈尔及同仁股份有限公司 | Bioabsorbable medical device |
Non-Patent Citations (1)
| Title |
|---|
| 高小龙等: "新型可降解食管支架的设计研究", 《中国医疗器械信息》 * |
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