CN116115835A - Bioabsorbable polymer stent and preparation method thereof - Google Patents

Abstract

The invention provides a bioabsorbable polymer stent and a preparation method thereof. The method comprises the following steps: s1: drying the raw materials, and then performing thermoforming processing treatment to obtain an original pipe; s2: and carrying out heat treatment crystallization on the original pipe to obtain the bioabsorbable polymer stent, wherein the heat treatment crystallization comprises melt crystallization or cold crystallization. The bioabsorbable polymer stent of the invention has high supporting force, low radial narrowing degree and low rebound; and the preparation method is simple and is easy to realize large-scale industrial production.

Description

Translated fromChinese

一种生物可吸收聚合物支架及其制备方法A kind of bioabsorbable polymer scaffold and preparation method thereof

技术领域technical field

本发明涉及复合材料技术领域，尤其涉及一种生物可吸收聚合物支架及其制备方法。The invention relates to the technical field of composite materials, in particular to a bioabsorbable polymer bracket and a preparation method thereof.

背景技术Background technique

冠心病是常见的一种心血管疾病，严重威胁人类生命健康，在美国等很多发达国家冠心病甚至排在死亡原因榜首，我国冠心病的患病率和死亡率也在不断攀升，冠心病是由于冠脉发生粥样硬化导致管腔狭窄或阻塞从而引起心肌缺血缺氧而坏死的一种疾病，因此寻求解决这一问题的方法至关重要。Coronary heart disease is a common cardiovascular disease that seriously threatens human life and health. In many developed countries such as the United States, coronary heart disease even ranks first in the list of causes of death. The prevalence and mortality of coronary heart disease in my country are also rising. Coronary heart disease is Atherosclerosis in the coronary artery leads to stenosis or obstruction of the lumen, which causes myocardial ischemia and hypoxia and necrosis. Therefore, it is very important to find a way to solve this problem.

生物可吸收支架是一种中空管状装置，冠状动脉内植入生物可吸收支架是现今治疗冠心病的一种常用手段，植入早期为血管提供径向支撑，防止血管的弹性回缩，后期完全吸收后其对血管的束缚被解除，从而有效地降低再狭窄率和血栓的形成。A bioabsorbable stent is a hollow tubular device. Implanting a bioabsorbable stent into a coronary artery is a common method for the treatment of coronary heart disease today. It provides radial support for the blood vessel in the early stage of implantation and prevents the elastic retraction of the blood vessel. After absorption, its binding to the blood vessels is released, thereby effectively reducing the rate of restenosis and the formation of thrombus.

生物可吸收支架包括生物可吸收聚合物支架和生物可吸收金属支架。目前，常用的生物可吸收聚合物支架可降解聚合物材料包括PLLA、PDLLA、聚己内酯、和聚乙交酯及其共聚物等。其中，主要以左旋聚乳酸(PLLA)或PLLA共混物(与其他生物可吸收材料共混)为基础材料，在植入体后可有效支撑狭窄血管，随后完全降解并被人体吸收。然而，PLLA植入血管一段时间后，会发生由于支架内部残留应力导致支架出现径向变窄的现象。产生这一现象的原因是，在生产过程中，支架原始管材经历了双向拉伸扩大直径的技术处理，在材料内部残留管材中心轴方向的材料内应力，内应力的存在使得支架趋向于恢复到变形前的尺寸状态，即径向变窄。植入血管内一段时间后，支架出现蠕变变形，径向变窄，支撑力减小，较小的支撑力将使得血管有再次狭窄的风险。Bioabsorbable stents include bioabsorbable polymer stents and bioabsorbable metal stents. Currently, commonly used degradable polymer materials for bioabsorbable polymer stents include PLLA, PDLLA, polycaprolactone, and polyglycolide and its copolymers. Among them, poly-L-lactic acid (PLLA) or PLLA blends (blended with other bioabsorbable materials) are mainly used as the basic material, which can effectively support narrow blood vessels after implantation, and then completely degrade and be absorbed by the human body. However, after the PLLA is implanted in the blood vessel for a period of time, the radial narrowing of the stent will occur due to the internal residual stress of the stent. The reason for this phenomenon is that during the production process, the original pipe material of the stent has undergone the technical treatment of biaxial stretching to expand the diameter, and the internal stress of the material in the direction of the central axis of the pipe remains inside the material. The existence of internal stress makes the stent tend to recover to Dimensional state before deformation, i.e. radial narrowing. After being implanted in the blood vessel for a period of time, the stent will creep and deform, radially narrow, and the supporting force will decrease, and the small supporting force will cause the risk of re-stenosis of the blood vessel.

为了获得足够的径向力，在支架设计过程中往往会选择增加支架筋的宽度和厚度，增加连接杆的宽度以及增加金属覆盖率等方法，而这些因素的改变，会同时改变支架的柔顺性、推送性、血流动力学等特性，造成支架整体性状的改变。但为了增加支撑强度而选择高屈服强度的支架材料，会造成球囊释放压力后支架的快速回弹，即有较高的弹性回缩率。In order to obtain sufficient radial force, methods such as increasing the width and thickness of the stent ribs, increasing the width of the connecting rods, and increasing the metal coverage are often chosen during the stent design process, and changes in these factors will simultaneously change the flexibility of the stent , pushability, hemodynamics and other characteristics, resulting in changes in the overall properties of the stent. However, choosing a scaffold material with a high yield strength in order to increase the support strength will cause the scaffold to rebound quickly after the balloon releases pressure, that is, it has a high elastic recoil rate.

CN102497970A公开了可降解管径向膨胀的方法。主要是通过使用热源沿着模具和管的圆柱轴平移，将模具加热至可降解管的变形温度，在可降解管内增加压力的作用下使可降解管沿径向膨胀而抵靠在所述模具的内表面上形成可降解管，提高了可降解管的径向强度，从而进一步提高基于可降解管所制造的可降解支架的径向强度。由于此法要求热源在较低的平移速度(例如0.2-1.2mm/s)平移，以使可降解管能获得足够的温度进行膨胀，加工效率较低。如制备200mm长的可降解管，需要至少5min。此外，由于可降解管径向膨胀的过程中，热源需要沿着模具和可降解管平移，因此，可降解管的长度受制于模具的长度限制，而模具的长度由于加工的限制不能做的很长，且可降解管从长模具的内表面拔出来也会非常困难，由此可见，CN102497970A所提供的方法不能制备较长的可降解管，且降低了制备可降解支架的效率。CN102497970A discloses a method for radial expansion of a degradable tube. Mainly by using a heat source to translate along the cylindrical axis of the mold and the tube, heating the mold to the deformation temperature of the degradable tube, under the action of increasing pressure in the degradable tube, the degradable tube radially expands against the mold The degradable tube is formed on the inner surface of the degradable tube, which improves the radial strength of the degradable tube, thereby further improving the radial strength of the degradable stent manufactured based on the degradable tube. Since this method requires the heat source to translate at a relatively low translation speed (for example, 0.2-1.2 mm/s), so that the degradable tube can obtain sufficient temperature for expansion, the processing efficiency is low. For example, it takes at least 5 minutes to prepare a 200mm long degradable tube. In addition, due to the radial expansion of the degradable tube, the heat source needs to translate along the mold and the degradable tube. Therefore, the length of the degradable tube is limited by the length of the mold, and the length of the mold cannot be made very large due to the limitation of processing. Long, and it will be very difficult to pull out the degradable tube from the inner surface of the long mold. It can be seen that the method provided by CN102497970A cannot prepare a long degradable tube, and reduces the efficiency of preparing the degradable stent.

CN102499999A公开了使可降解管径向形变的方法，将可降解管置于传热模具中，加热模具在传热模具外部轴向移动对可降解管进行预加热，采用机械芯轴在可降解管内部旋进，使可降解管径向扩张以形成可降解管。此法同样要求芯轴轴向移动的速度较低(0.2～1mm/s)，可降解管长度受制于传热模具的长度限制，不能制备较长的可降解管，降低了制备可降解支架的效率。CN102499999A discloses a method for radially deforming a degradable tube. The degradable tube is placed in a heat transfer mold, and the heating mold moves axially outside the heat transfer mold to preheat the degradable tube. Internal screwing radially expands the degradable tube to form the degradable tube. This method also requires that the axial movement speed of the mandrel is low (0.2-1mm/s), and the length of the degradable tube is limited by the length of the heat transfer mold, so it is impossible to prepare a long degradable tube, which reduces the cost of preparing the degradable stent. efficiency.

CN102210616A公开了一种可降解支架的制备方法，通过将可降解管的原材料加工成型为可降解管形状，具体通过挤出工艺或注塑工艺制备可降解管的形状。这里挤出工艺可以制备足够长度的可降解管，但其没有快速降温至“玻璃化转变温度”的过程，管体从熔融状态开始缓慢降温，降温方式包括水冷和风冷，管体在熔融状态下，受到重力、气流、水流的影响，很难保持均匀的尺寸，可操作性较低，废品率极高。CN102210616A discloses a method for preparing a degradable stent. The raw material of the degradable tube is processed and shaped into the shape of the degradable tube, specifically, the shape of the degradable tube is prepared by an extrusion process or an injection molding process. The extrusion process here can produce a degradable tube of sufficient length, but it does not have a rapid cooling process to the "glass transition temperature". The tube body starts to cool down slowly from the molten state. The cooling methods include water cooling and air cooling. The tube body is in the molten state. Under the influence of gravity, airflow, and water flow, it is difficult to maintain a uniform size, the operability is low, and the scrap rate is extremely high.

CN102497970A公开了控制生物可吸收支架的结晶形态，包括一种用于制造支架的方法，提供PLLA管而将其安置在圆柱形模具内；而且通过对整个模具和管加热的热源将模具和管加热，例如立刻加热至管变形温度；在管内增加压力；允许管内增加的压力使所述管径向膨胀而抵靠在模具的内表面上，且随后通过冷却源立刻冷却整个模具和管体，但其未有有效的消除应力的操作，使其管体在人体温度下容易发生径向回弹。CN102497970A discloses controlling the crystalline morphology of a bioabsorbable scaffold, including a method for manufacturing a scaffold, providing a PLLA tube to be placed in a cylindrical mold; and heating the mold and tube by a heat source that heats the entire mold and tube , such as immediately heating to the tube deformation temperature; increasing the pressure inside the tube; allowing the increased pressure inside the tube to expand the tube radially against the inner surface of the mold, and then cooling the entire mold and tube body at once by a cooling source, but It has no effective stress relief operation, so that the pipe body is prone to radial rebound at human body temperature.

因此，急需一种径向支撑力高且弹性回缩率低的新型生物可降解支架。Therefore, there is an urgent need for a new type of biodegradable scaffold with high radial support force and low elastic recoil.

发明内容Contents of the invention

针对现有技术中所存在的不足，本发明提供了一种生物可吸收聚合物支架及其制备方法，其解决了现有生物可吸收聚合物支架存在的在提高径向支撑力的同时会导致径向回弹高的问题。Aiming at the deficiencies in the prior art, the present invention provides a bioabsorbable polymer stent and a preparation method thereof, which solves the problems existing in the existing bioabsorbable polymer stent while increasing the radial support force and causing The problem of high radial rebound.

本发明一方面，提供一种生物可吸收聚合物支架的制备方法，包括以下步骤：One aspect of the present invention provides a method for preparing a bioabsorbable polymer scaffold, comprising the following steps:

S1：将原料干燥，之后进行热成型加工处理，得到原始管材；S1: Dry the raw material, and then perform thermoforming processing to obtain the original pipe;

S2：将原始管材进行热处理结晶得到生物可吸收聚合物支架，所述热处理结晶包括熔体结晶或冷结晶。S2: performing heat treatment crystallization on the original pipe material to obtain the bioabsorbable polymer scaffold, the heat treatment crystallization includes melt crystallization or cold crystallization.

进一步地，所述熔体结晶包括将原始管材置于热水槽进行真空冷却，所述真空冷却温度为70-90℃，冷却时间为30min-2h,之后通过牵引机进行牵引拉伸，再缓慢冷却至室温；Further, the crystallization of the melt includes placing the original pipe in a hot water tank for vacuum cooling, the vacuum cooling temperature is 70-90°C, and the cooling time is 30min-2h, and then stretched by a tractor, and then slowly cooled to room temperature;

或所述冷结晶包括将原始管材先置于冷水槽进行冷却定型，所述冷却定型温度为15-35℃，之后通过牵引机进行牵引拉伸，再置于加热室进行加热处理，所述加热处理的温度为70-80℃，时间为1-5h，再缓慢降至室温。Or the cold crystallization includes placing the original pipe in a cold water tank for cooling and setting, the cooling and setting temperature is 15-35°C, and then drawing and stretching by a tractor, and then placing it in a heating room for heat treatment, the heating The treatment temperature is 70-80°C, the time is 1-5h, and then slowly lowered to room temperature.

进一步地，步骤S1中，所述干燥温度为40℃-70℃，干燥时间为4-20h。Further, in step S1, the drying temperature is 40°C-70°C, and the drying time is 4-20h.

进一步地，步骤S1中，所述热成型加工处理的温度为180-220℃。Further, in step S1, the temperature of the thermoforming processing is 180-220°C.

进一步地，所述热成型加工包括挤出吹塑、注塑吹塑、熔体纺丝中的一种或几种。Further, the thermoforming process includes one or more of extrusion blow molding, injection blow molding, and melt spinning.

进一步地，按质量百分比计，所述原料包括聚酯聚合物60-100％；不可生物降解的聚合物0-40％。Further, in terms of mass percentage, the raw material includes 60-100% of polyester polymer and 0-40% of non-biodegradable polymer.

进一步地，所述聚酯聚合物包括聚L-乳酸、聚D,L-乳酸、聚乙交酯、聚丙交酯、聚己内酯及其共聚物中的一种或几种，优选地，包括聚(L-乳酸/D,L-乳酸)、聚(乙交酯/丙交酯)、聚乙丙交酯、聚(L-乳酸/己内酯)、聚(乙交酯/己内酯)、聚(D,L-乳酸/己内酯)。Further, the polyester polymer includes one or more of poly L-lactic acid, poly D, L-lactic acid, polyglycolide, polylactide, polycaprolactone and their copolymers, preferably, Including poly(L-lactic acid/D,L-lactic acid), poly(glycolide/lactide), polyglycolide, poly(L-lactic acid/caprolactone), poly(glycolide/caprolactone esters), poly(D,L-lactic acid/caprolactone).

进一步地，所述不可生物降解的聚合物包括聚氨酯、聚甲基丙烯酸正丁酯、乙烯-醋酸乙烯共聚物、聚(苯乙烯-b-异丁烯-b-苯乙烯)中的一种或几种。Further, the non-biodegradable polymer includes one or more of polyurethane, poly-n-butyl methacrylate, ethylene-vinyl acetate copolymer, poly(styrene-b-isobutylene-b-styrene) .

进一步地，所述原料由聚乳酸和聚氨酯组成，Further, the raw material is composed of polylactic acid and polyurethane,

优选地，聚乳酸和聚氨酯的质量比为7：3。Preferably, the mass ratio of polylactic acid and polyurethane is 7:3.

本发明另一方面，提供一种生物可吸收聚合物支架，通过上述方法制备得到。Another aspect of the present invention provides a bioabsorbable polymer scaffold prepared by the above method.

其中，所述生物可吸收聚合物支架的管腔直径为1-5mm,壁厚为0.1-0.3mm。Wherein, the lumen diameter of the bioabsorbable polymer stent is 1-5 mm, and the wall thickness is 0.1-0.3 mm.

本发明的技术原理为：本发明中的原料经挤出机料筒加热至熔点以上，形成粘流态，后经螺杆推送及模具限位，熔体形成原始管材进入水中，并在水中冷却定型。The technical principle of the present invention is: the raw material in the present invention is heated above the melting point by the barrel of the extruder to form a viscous flow state, and then pushed by the screw and limited by the mold, the melt forms the original pipe and enters the water, and is cooled and shaped in the water .

根据冷却水的不同温度，其具体技术原理如下：According to the different temperatures of the cooling water, the specific technical principles are as follows:

1、熔体结晶：熔体经模具挤出后，进入到温度70-90℃的冷却水中结晶。在熔体结晶过程中，熔体中聚合物分子随着温度降低运动越来越慢，最后形成一个晶核。成核后聚合物分子再围绕晶核成长，形成结晶成长过程。冷却温度是影响结晶质量和结晶速度的关键因素，此处使用的冷却水温度应设置在原材料的“玻璃化转变温度”附近。1. Melt crystallization: After the melt is extruded through the mold, it enters the cooling water at a temperature of 70-90°C to crystallize. During the melt crystallization process, the polymer molecules in the melt move slower and slower as the temperature decreases, and finally form a crystal nucleus. After nucleation, polymer molecules grow around the crystal nucleus to form a crystal growth process. Cooling temperature is a key factor affecting crystallization quality and crystallization speed, and the cooling water temperature used here should be set near the "glass transition temperature" of the raw material.

2、冷结晶：熔体经模具挤出后，进入到温度15-35℃的冷却水中定型，并经牵引机牵引切割定长，随后将管材放置于70-80℃的加热室中继续处理1-5h。在冷结晶过程中，熔体中聚合物熔融后再骤冷降温，这个过程中结晶度很低，形成玻璃态的状态。之后再升温，固态的聚合物中冻结的分子逐渐能够运动，从而发生结晶。升温温度是影响结晶质量和结晶速度的关键因素。2. Cold crystallization: After the melt is extruded through the mold, it enters the cooling water at a temperature of 15-35°C to be shaped, and is drawn and cut to length by a tractor, and then the pipe is placed in a heating room at 70-80°C to continue processing 1 -5h. In the cold crystallization process, the polymer in the melt is melted and then cooled down rapidly. During this process, the degree of crystallinity is very low and a glassy state is formed. Then, when the temperature is raised again, the frozen molecules in the solid polymer are gradually able to move, so that crystallization occurs. Heating temperature is a key factor affecting crystallization quality and crystallization speed.

综上可知，本发明中的两种结晶方法，均可促进材料的结晶度，制备出具有小尺寸晶体、更高结晶度、更易消除内应力的管体，使得管体不仅具有增强的径向力，而且减小了弹性回缩。进一步，发明人还发现，冷结晶中加热室的处理不仅可以使得管体充分结晶，而且可以有足够的时间使得晶体进行缺陷修复；并可以更有效的消除管体的内应力，防止管体后期因内应力影响而产生形变。更重要的是，与聚乳酸管体材料相比，当管体材料为70％的聚乳酸和30％的聚氨酯时，管体的弹性回缩最小，同时径向支撑力与聚乳酸材料管体相当。In summary, the two crystallization methods in the present invention can both promote the crystallinity of the material, and prepare a tube body with small-sized crystals, higher crystallinity, and easier elimination of internal stress, so that the tube body not only has enhanced radial force, and reduces elastic recoil. Further, the inventors also found that the treatment of the heating chamber in the cold crystallization can not only fully crystallize the tube body, but also allow enough time for the crystal to repair defects; and can more effectively eliminate the internal stress of the tube body and prevent the tube body from being damaged in the later stage. Deformation due to the influence of internal stress. More importantly, compared with the PLA tube body material, when the tube body material is 70% PLA and 30% polyurethane, the elastic recoil of the tube body is the smallest, while the radial support force is the same as that of the PLA material tube body. quite.

本发明具有以下有益效果：The present invention has the following beneficial effects:

本发明方法制备的支架，具有较高的结晶度，内应力已完全消除，因此，支架具有良好的支撑力，并且可避免支架的回缩。The stent prepared by the method of the invention has high crystallinity and the internal stress has been completely eliminated, so the stent has good supporting force and can avoid retraction of the stent.

具体实施方式Detailed ways

下面结合实施例对本发明中的技术方案进一步说明。The technical solution in the present invention will be further described below in conjunction with the embodiments.

实施例1生物可吸收聚合物支架的制备The preparation of embodiment 1 bioabsorbable polymer scaffold

1、选择PLLA(聚乳酸)为原料，将PLLA放置于真空烘箱中真空干燥，真空度-0.095Mpa，温度65℃，干燥时间6h。1. Select PLLA (polylactic acid) as the raw material, place PLLA in a vacuum oven for vacuum drying, the vacuum degree is -0.095Mpa, the temperature is 65°C, and the drying time is 6h.

2、使用精密挤出机对步骤1中所述烘干后的原料进行挤出，挤出温度设置温度梯度，从进料口到出料口温度为160-200℃，原料经高温料筒和模具加热，转变为均一的熔体状态，同时，在挤出机螺杆的推送下，熔体经挤出机模具出料口挤出。2. Use a precision extruder to extrude the dried raw materials described in step 1. The extrusion temperature is set with a temperature gradient. The temperature from the inlet to the outlet is 160-200°C. The raw materials are passed through the high-temperature barrel and The mold is heated and transformed into a uniform melt state. At the same time, under the push of the extruder screw, the melt is extruded through the outlet of the extruder mold.

3、步骤2所述的模具出口，芯棒中设置有通气孔，通气孔连接在氮气瓶上，氮气经流量阀以一定的流量通向芯棒，以实现熔体为中空、圆柱形。3. At the mold outlet described in step 2, a vent hole is provided in the mandrel, and the vent hole is connected to the nitrogen bottle, and the nitrogen gas passes through the flow valve to the mandrel at a certain flow rate, so that the melt is hollow and cylindrical.

4、熔体挤出模具后，迅速进入温度为25±2℃的冷却水中，冷却水以冷水机循环的形式保持恒温，冷水槽长度为5m。4. After the melt is extruded from the mold, it quickly enters the cooling water with a temperature of 25±2°C. The cooling water is kept at a constant temperature in the form of a chiller circulation, and the length of the cold water tank is 5m.

5、熔体经水槽内冷却水快速冷却定型后，连接至牵引机处，以保证稳定而持久的牵引，从而实现管体尺寸均一。调整牵引机牵引速率及氮气流量，使管体尺寸为外径3.0mm，壁厚0.12mm，同时设置管体长度为1m，牵引机将根据牵引长度自动将管体切割。5. After the melt is rapidly cooled and shaped by the cooling water in the water tank, it is connected to the traction machine to ensure stable and long-lasting traction, so as to achieve uniform pipe size. Adjust the traction speed and nitrogen flow of the tractor so that the outer diameter of the pipe body is 3.0mm and the wall thickness is 0.12mm. At the same time, the length of the pipe body is set to 1m, and the tractor will automatically cut the pipe body according to the traction length.

6、经切割后的管体转移至80℃加热室中，管体垂直悬挂，以防止加热不均造成的管体变形，热处理时间为2h，热处理完毕后，加热室缓慢降温至室温，降温速度为5℃/min。6. The cut pipe body is transferred to a heating chamber at 80°C, and the pipe body is hung vertically to prevent deformation of the pipe body caused by uneven heating. The heat treatment time is 2 hours. After the heat treatment is completed, the heating chamber is slowly cooled to room temperature. 5°C/min.

7、从降至室温的加热室中取出管体，即为支架基体，可用于后续的激光切割制备支架。7. Take out the tube body from the heating chamber lowered to room temperature, which is the stent matrix, which can be used for subsequent laser cutting to prepare stents.

实施例2生物可吸收聚合物支架的制备Embodiment 2 Preparation of bioabsorbable polymer scaffold

1组：与实施例1类似，不同之处在于：原料为30％PLLA(聚乳酸)和70％TPU(聚胺酯)。Group 1: similar to Example 1, except that the raw materials are 30% PLLA (polylactic acid) and 70% TPU (polyurethane).

具体如下：details as follows:

1、选择PLLA(聚乳酸)为原料，将PLLA放置于真空烘箱中真空干燥，真空度-0.095Mpa，温度65℃，干燥时间6h。将TPU(聚胺酯)放置于真空烘箱中真空干燥，真空度-0.095Mpa，温度85℃，干燥时间6h。1. Select PLLA (polylactic acid) as the raw material, place PLLA in a vacuum oven for vacuum drying, the vacuum degree is -0.095Mpa, the temperature is 65°C, and the drying time is 6h. Place the TPU (polyurethane) in a vacuum oven for vacuum drying, the vacuum degree is -0.095Mpa, the temperature is 85°C, and the drying time is 6h.

2、使用机械混料机对PLLA和TPU进行机械共混，作为优选PLLA和TPU的质量比为7:3。其余步骤与实施例1相同。2. Use a mechanical mixer to mechanically blend PLLA and TPU, preferably with a mass ratio of PLLA and TPU of 7:3. All the other steps are the same as in Example 1.

2组：与实施例1类似，不同之处在于：步骤4中冷却水温度为15℃；Group 2: similar to Example 1, the difference is that the temperature of the cooling water in step 4 is 15°C;

3组：与实施例1类似，不同之处在于：步骤4中冷却水温度为35℃；Group 3: Similar to Example 1, the difference is that the temperature of the cooling water in step 4 is 35°C;

4组：与实施例1类似，不同之处在于：步骤6中加热室温度为70℃，时间为5h；Group 4: similar to Example 1, the difference is that in step 6, the temperature of the heating chamber is 70°C, and the time is 5h;

5组：与实施例1类似，不同之处在于：步骤6中加热室温度为70℃，时间为5h；Group 5: similar to Example 1, the difference is: in step 6, the temperature of the heating chamber is 70°C, and the time is 5h;

实施例3生物可吸收聚合物支架的制备Embodiment 3 Preparation of bioabsorbable polymer scaffold

1、选择PLLA(聚乳酸)为原料，将PLLA放置于真空烘箱中真空干燥，真空度-0.095Mpa，温度65℃，干燥时间6h。将TPU(聚胺酯)放置于真空烘箱中真空干燥，真空度-0.095Mpa，温度85℃，干燥时间6h。1. Select PLLA (polylactic acid) as the raw material, place PLLA in a vacuum oven for vacuum drying, the vacuum degree is -0.095Mpa, the temperature is 65°C, and the drying time is 6h. Place the TPU (polyurethane) in a vacuum oven for vacuum drying, the vacuum degree is -0.095Mpa, the temperature is 85°C, and the drying time is 6h.

2、使用机械混料机对PLLA和TPU进行机械共混，作为优选PLLA和TPU的质量比为7:3。2. Use a mechanical mixer to mechanically blend PLLA and TPU, preferably with a mass ratio of PLLA and TPU of 7:3.

3、使用精密挤出机对步骤2中所述共混后的原料进行挤出，挤出温度设置温度梯度，从进料口到出料口温度为160-200℃，原料经高温料筒和模具加热，转变为均一的熔体状态，同时，在挤出机螺杆的推送下，熔体经挤出机模具出料口挤出。3. Use a precision extruder to extrude the blended raw materials described in step 2. The extrusion temperature is set to a temperature gradient. The temperature from the inlet to the outlet is 160-200°C. The raw materials are passed through a high-temperature barrel and The mold is heated and transformed into a uniform melt state. At the same time, under the push of the extruder screw, the melt is extruded through the outlet of the extruder mold.

4、步骤2所述的模具出口，芯棒中设置有通气孔。4. At the outlet of the mold described in step 2, vent holes are provided in the mandrel.

5、熔体挤出模具后，迅速进入温度为80±2℃的热水槽中，热水以加热棒控温的形式保持恒温，热水槽长度为10m，时间为1h。5. After the melt is extruded from the mold, it quickly enters a hot water tank with a temperature of 80±2°C. The hot water is kept at a constant temperature by means of a heating rod. The length of the hot water tank is 10m and the time is 1h.

6、冷却水槽为真空水槽，使用定径套对挤出的熔体进行定型，真空的环境可保证熔体贴壁定径套，实现管材轮廓为正圆。6. The cooling water tank is a vacuum water tank, and the sizing sleeve is used to shape the extruded melt. The vacuum environment can ensure that the melt adheres to the sizing sleeve, and the contour of the pipe is a perfect circle.

7、熔体经热水槽热处理后，连接至牵引机处，以保证稳定而持久的牵引，从而实现管体尺寸均一。调整牵引机牵引速率，使管体尺寸为外径3.0mm，壁厚0.12mm同时设置管体长度为1m，牵引机将根据牵引长度自动将管体切割。7. After the melt is heat-treated in the hot water tank, it is connected to the traction machine to ensure stable and long-lasting traction, so as to achieve uniform pipe size. Adjust the traction speed of the tractor so that the pipe body size is 3.0mm in outer diameter and 0.12mm in wall thickness. At the same time, set the length of the pipe body to 1m, and the tractor will automatically cut the pipe body according to the traction length.

8、经切割后的管体转移至悬挂架上，管体垂直悬挂，以防止冷却不均造成的管体变形，冷却时间为1h，从悬挂架上取下管体，即为支架基体，可用于后续的激光切割。8. The cut pipe body is transferred to the suspension frame, and the pipe body is hung vertically to prevent the deformation of the pipe body caused by uneven cooling. The cooling time is 1 hour. for subsequent laser cutting.

实施例4生物可吸收聚合物支架的制备Embodiment 4 Preparation of bioabsorbable polymer scaffold

1组：与实施例3类似，不同之处在于：步骤5中温度为70℃，时间为2h；Group 1: similar to Example 3, the difference is: in step 5, the temperature is 70°C and the time is 2h;

2组：与实施例3类似，不同之处在于：步骤5中温度为90℃，时间为0.5h。Group 2: similar to Example 3, except that in step 5, the temperature is 90°C and the time is 0.5h.

对比例1Comparative example 1

与实施例1类似，不同之处在于：步骤6中，加热室温度为60℃。Similar to Example 1, the difference is that in Step 6, the temperature of the heating chamber is 60°C.

对比例2Comparative example 2

与实施例1类似，不同之处在于：步骤6中，加热室温度为100℃。Similar to Example 1, the difference is that in Step 6, the temperature of the heating chamber is 100°C.

对比例3Comparative example 3

与实施例1类似，不同之处在于：不包括步骤6、7。Similar to Embodiment 1, the difference is that steps 6 and 7 are not included.

从牵引机上收取管体后，即为支架基体，可用于后续的激光切割制备支架。After the tube body is collected from the tractor, it is the stent matrix, which can be used for subsequent laser cutting to prepare the stent.

对比例4Comparative example 4

按照专利CN106361465A实施例1的方式制备外径3.0mm，壁厚0.12mm的管体。A pipe body with an outer diameter of 3.0 mm and a wall thickness of 0.12 mm was prepared according to the method of Example 1 of patent CN106361465A.

试验例生物可吸收聚合物支架的物理力学性能Physical and Mechanical Properties of Test Example Bioabsorbable Polymer Scaffold

1、径向回弹测试1. Radial rebound test

按照标准YY/T0473-2004《外科植入物聚交酯共聚物和共混物体外降解实验》4.2.1配制磷酸盐缓冲液。按照缓冲液体积(毫升)和管体质量(克)比值30:1的比例，将管体浸泡在缓冲液中，并以37℃水浴处理。Phosphate buffer was prepared according to 4.2.1 of the standard YY/T0473-2004 "In vitro degradation experiment of polylactide copolymers and blends for surgical implants". According to the ratio of the buffer volume (ml) to the tube body mass (g) ratio of 30:1, soak the tube body in the buffer solution and treat it in a 37°C water bath.

2、支撑力性能测试2. Support performance test

使用支架支撑力测试仪对管体施加持续的压力(推进速度0.1mm/s),直至支架直径变化率达到10％，记录这一测试过程中最大压力值,单位以毫米汞柱(mmHg)表示。Use the stent support force tester to apply continuous pressure to the tube body (propelling speed 0.1mm/s) until the diameter change rate of the stent reaches 10%, record the maximum pressure value during this test, and the unit is expressed in millimeters of mercury (mmHg) .

3、结晶度测试3. Crystallinity test

结晶度采用ISO11357-1-2016标准方法测定。The degree of crystallinity was measured by ISO11357-1-2016 standard method.

DSC测试方法具体为：测试聚合物的DSC曲线，得到熔融曲线和基线包围的面积，换算成热量，即为聚合物结晶部分的熔融热，聚合物结晶部分熔融热比100％结晶时的理论熔融热焓，即为此聚合物的结晶度。The DSC test method is specifically: test the DSC curve of the polymer, obtain the area surrounded by the melting curve and the baseline, convert it into heat, that is, the melting heat of the polymer crystallization part, the melting heat of the polymer crystallization part is more than the theoretical melting when 100% crystallization Enthalpy, which is the degree of crystallinity of the polymer.

管体各径向回弹数据、径向支撑力和结晶度如表1所示。The radial springback data, radial support force and crystallinity of the pipe body are shown in Table 1.

表1径向回弹性能检测Table 1 Radial rebound performance test

由以上结果可知，实施例2中1组的回弹系数明显低于实施例1，这可能是由于管材中30％TPU弹性体的存在，使得PLLA分子链的运动能力更强，在相同结晶环境下，PLLA和TPU在微观上形成了“海-岛”状结构，以PLLA为骨架，TPU分散在PLLA基体中，使得PLLA的结晶度更高，消除内应力的效果更好，从而使该组管材在保持了足够的径向支撑力，并且该组管材的径向支撑力上与纯PLLA无明显差异的同时，还保持了回弹系数最低。From the above results, it can be seen that the rebound coefficient of Group 1 in Example 2 is significantly lower than that of Example 1, which may be due to the presence of 30% TPU elastomer in the pipe, which makes the PLLA molecular chain more mobile. In the same crystallization environment Next, PLLA and TPU form a "sea-island" structure on the microscopic scale, with PLLA as the skeleton, and TPU dispersed in the PLLA matrix, which makes the crystallinity of PLLA higher and the effect of eliminating internal stress is better, so that the group While the pipes maintain sufficient radial support force, and the radial support force of this group of pipes has no significant difference from pure PLLA, it also maintains the lowest rebound coefficient.

对比例1中，虽然管材回弹系数较小，但由于加热室温度过低，结晶度低，管材径向支撑力过低。对比例2中，热处理温度(100℃)较高，管材受重力影响出现形变，不具备可检测性。对比例3未经过加热室处理，虽然回弹系数小，但结晶度低，管材径向支撑力较低。对比例4中经膨胀拉伸后的管体，有明显的回弹现象，其数据远高于实施例1。In Comparative Example 1, although the coefficient of resilience of the pipe is small, the radial support force of the pipe is too low due to the low heating room temperature and low crystallinity. In Comparative Example 2, the heat treatment temperature (100° C.) was relatively high, and the pipe material was deformed under the influence of gravity, which was not detectable. Comparative example 3 has not been treated in a heating chamber. Although the coefficient of resilience is small, the degree of crystallinity is low, and the radial support force of the pipe is low. The expanded and stretched pipe body in Comparative Example 4 has obvious rebound phenomenon, and its data is much higher than that of Example 1.

最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。Finally, it is noted that the above embodiments are only used to illustrate the technical solutions of the present invention without limitation. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be carried out Modifications or equivalent replacements without departing from the spirit and scope of the technical solution of the present invention shall be covered by the claims of the present invention.

Claims (10)

1. A method for preparing a bioabsorbable polymeric stent, characterized by: the method comprises the following steps:

s1: drying the raw materials, and then performing thermoforming processing treatment to obtain an original pipe;

s2: and carrying out heat treatment crystallization on the original pipe to obtain the bioabsorbable polymer stent, wherein the heat treatment crystallization comprises melt crystallization or cold crystallization.

2. A method of preparing a bioabsorbable polymeric stent as claimed in claim 1, wherein: the melt crystallization comprises the steps of placing an original pipe in a hot water tank for vacuum cooling, wherein the vacuum cooling temperature is 70-90 ℃, the cooling time is 30min-2h, then, carrying out traction and stretching by a traction machine, and then, slowly cooling to the room temperature;

or the cold crystallization comprises the steps of firstly placing the original pipe in a cold water tank for cooling and shaping, wherein the cooling and shaping temperature is 15-35 ℃, then drawing and stretching by a tractor, then placing in a heating chamber for heating, wherein the heating temperature is 70-80 ℃ for 1-5h, and then slowly cooling to room temperature.

3. A method of preparing a bioabsorbable polymeric stent as claimed in claim 1, wherein: in the step S1, the drying temperature is 40-70 ℃ and the drying time is 4-20h.

4. A method of preparing a bioabsorbable polymeric stent as claimed in claim 1, wherein: in the step S1, the temperature of the thermoforming processing treatment is 160-220 ℃.

5. A method of preparing a bioabsorbable polymeric stent as claimed in claim 1, wherein: in step S1, the thermoforming process includes one or more of extrusion blow molding, injection blow molding, and melt spinning.

6. A method of preparing a bioabsorbable polymeric stent as claimed in claim 1, wherein: the raw materials comprise 60-100% of polyester polymer by mass percent; 0-40% of non-biodegradable polymer.

7. A method of preparing a bioabsorbable polymeric stent as claimed in claim 6, wherein: the polyester polymer comprises one or more of poly L-lactic acid, poly D, L-lactic acid, polyglycolide, polylactide, polycaprolactone and copolymers thereof, preferably poly (L-lactic acid/D, L-lactic acid), poly (glycolide/lactide), poly (glycolide), poly (L-lactic acid/caprolactone), poly (glycolide/caprolactone), poly (D, L-lactic acid/caprolactone).

8. A method of preparing a bioabsorbable polymeric stent as claimed in claim 6, wherein: the non-biodegradable polymer comprises one or more of polyurethane, poly-n-butyl methacrylate, ethylene-vinyl acetate copolymer and poly (styrene-b-isobutene-b-styrene).

9. A method of preparing a bioabsorbable polymeric stent as claimed in claim 6, wherein: the raw materials consist of polylactic acid and polyurethane,

preferably, the mass ratio of polylactic acid to polyurethane is 7:3.

10. a bioabsorbable polymeric stent, characterized by: a method of preparing a bioabsorbable polymer stent of claims 1-9.