技术领域technical field
本发明涉及一种降解速率可控的可降解封堵器的制备方法，属于医疗器械技术领域。The invention relates to a preparation method of a degradable occluder with controllable degradation rate, belonging to the technical field of medical devices.
背景技术Background technique
非晶态聚物有三种力学状态，它们是玻璃态、高弹态和粘流态。在玻璃化转变温度Tg以下，高聚物处于玻璃态，为刚性固体，在外力作用下只会发生非常小的形变；在熔融温度Tm以上，高聚物处于黏流态，材料逐渐变成粘性的流体，此时形变不可能恢复；在玻璃化转变温度Tg以上，熔融温度Tm以下，高聚物处于高弹态，材料的弹性形变量明显地增加，并在这个温度区间形变相对稳定。很多高分子材料具备超弹性就是利用了他们在高弹态所表现出来的优异性能。Amorphous polymers have three mechanical states, which are glassy, elastic, and viscous. Below the glass transition temperatureTg , the polymer is in a glassy state and is a rigid solid, which only undergoes very small deformation under the action of an external force; above the melting temperatureTm , the polymer is in a viscous fluid state, and the material gradually changes. It is a viscous fluid, and the deformation cannot be restored at this time; above the glass transition temperature Tg and below the melting temperature Tm , the polymer is in a highly elastic state, and the elastic deformation of the material increases significantly, and the deformation in this temperature range relatively stable. Many polymer materials have superelasticity because of their excellent performance in the high elastic state.
传统封堵器使用的是具有超弹性和形状记忆性的NiTi合金丝编织，而金属材料最大的缺点就是不可降解，术后存在心律失常、传导阻滞、Ni离子析出、瓣膜损伤等问题。植入患者心脏后患者需终身携带，对人体的远期安全性尚缺乏数据支持。特别是儿童，心脏还在不断发育，封堵器的远期安全性还没有长期随访资料的证明。Traditional occluders use NiTi alloy wire braid with superelasticity and shape memory, but the biggest disadvantage of metal materials is that they are not degradable, and there are problems such as arrhythmia, conduction block, Ni ion precipitation, and valve damage after surgery. After being implanted in the patient's heart, the patient needs to carry it for life, and there is still a lack of data support for the long-term safety of the human body. Especially for children, the heart is still developing, and the long-term safety of the occluder has not been proved by long-term follow-up data.
目前，常用于制作可降解封堵器的生物可降解材料主要包括：聚乳酸系列(PLA类，聚左旋乳酸PLLA在缓冲溶液中的降解曲线如图2所示)、聚对二氧环己酮(PDO)、聚羟基乙酸(PGA，聚羟基乙酸PGA在缓冲溶液中的降解曲线如图3所示)、聚己内酯(PCL)、聚羟基丁酸酯(PHB)等。PDO高分子材料的玻璃化转变温度(Tg)约为-10℃，较低，熔融温度(Tm)约为100℃，因此在室温条件(20℃左右)下处于高弹态，比较柔软，利于编织。PPO是结晶聚合物，结晶度在37％左右，熔点大约为110℃，其抗张强度、降解过程中强度保留率大、打结强度等性能都较好。而PLA类材料虽然生物相容性好，力学性能优异，降解周期慢，但是玻璃化转变温度(Tg)在50～60℃，略高，因此在室温条件下处于玻璃态，比较硬，不利于编织，在可降解领域应用中多作为管材，通过激光切割的纺织对其加工后定型，例如可降解支架。PGA类材料，玻璃化转变温度为35℃左右，柔性差，虽然结晶度高，但是在空气中易吸潮降解，不易保存，降解速率较快，植入组织15天后开始吸收，30天后大量吸收，60～90天完全吸收，机械性能丧失较快，不适合制作封堵器(聚羟基乙酸在缓冲溶液中的降解曲线如图3所示)。聚己内酯(PCL)的玻璃化转变温度低，为-60℃，材质柔软，但是降解周期长，降解非常缓慢。1年内仅分子量降低，2年左右材料开始降解为碎片，3～5年完全降解。如图1所示，为大鼠体内PCL的分子量随时间的变化数据图表。At present, biodegradable materials commonly used to make degradable occluders mainly include: polylactic acid series (PLA type, the degradation curve of poly-L-lactic acid PLLA in buffer solution is shown in Figure 2), polydioxanone (PDO), polyglycolic acid (PGA, the degradation curve of polyglycolic acid PGA in buffer solution is shown in Figure 3), polycaprolactone (PCL), polyhydroxybutyrate (PHB) and so on. The glass transition temperature (Tg) of PDO polymer material is about -10°C, which is relatively low, and the melting temperature (Tm) is about 100°C, so it is in a high elastic state at room temperature (about 20°C), which is relatively soft and beneficial weave. PPO is a crystalline polymer with a crystallinity of about 37% and a melting point of about 110°C. Its tensile strength, high strength retention rate during degradation, and knot strength are all good. Although PLA materials have good biocompatibility, excellent mechanical properties, and slow degradation cycle, their glass transition temperature (Tg) is slightly higher at 50-60°C, so they are in a glassy state at room temperature and are relatively hard, which is not conducive to Braiding is mostly used as a tube in the degradable field, and it is shaped by laser-cut textiles, such as degradable stents. PGA material has a glass transition temperature of about 35°C and poor flexibility. Although it has high crystallinity, it is easy to absorb moisture and degrade in the air, is not easy to store, and has a fast degradation rate. It begins to absorb after 15 days of implantation, and absorbs a lot after 30 days. , completely absorbed in 60-90 days, the mechanical properties are lost quickly, and it is not suitable for making occluders (the degradation curve of polyglycolic acid in buffer solution is shown in Figure 3). Polycaprolactone (PCL) has a low glass transition temperature of -60°C, and the material is soft, but the degradation cycle is long and the degradation is very slow. Only the molecular weight decreases within 1 year, the material begins to degrade into fragments in about 2 years, and completely degrades in 3 to 5 years. As shown in FIG. 1 , it is a data chart of the molecular weight of PCL in rats over time.
PDO/PPDO poly(p-dioxanone)是聚对二氧环己酮的缩写。于20世纪70年代末由美国Ethicon公司开发了商品名为PDS的外科手术缝合线，它为单丝结构，特殊的表面结构使得其对伤口的损害小，降解性能好，柔性高于其他聚GA缝合线，有着独特的优越性。PDO/PPDO poly(p-dioxanone) is an abbreviation for polydioxanone. In the late 1970s, Ethicon Corporation of the United States developed a surgical suture named PDS, which has a monofilament structure. The special surface structure makes it less harmful to the wound, has good degradation performance, and is more flexible than other polyGAs. Sutures have unique advantages.
PDO的降解是一个水解过程，水解的快慢部分取决于水分子与酯键作用的难易程度。PDO纤维降解的较为平缓，在降解初期能保持一个较好的强度。随着水解的进行，材料的非晶区以及取向结构遭到了破坏，材料强度急剧下降，直到最后晶区发生降解。PDO在人体内最终可以完全分解成二氧化碳和水，无化学残留，被广泛用于医疗美容的埋线提升术中。The degradation of PDO is a hydrolysis process, and the speed of hydrolysis partly depends on the difficulty of the interaction between water molecules and ester bonds. The degradation of PDO fiber is relatively gentle, and it can maintain a good strength in the initial stage of degradation. As the hydrolysis proceeds, the amorphous region and orientation structure of the material are destroyed, and the strength of the material drops sharply until the final crystalline region degrades. PDO can be completely decomposed into carbon dioxide and water in the human body, without chemical residue, and is widely used in thread embedding surgery for medical cosmetology.
目前，上海形状记忆合金材料有限公司研发的可降解封堵器使用的材料主要为：1.编织丝材(聚对二氧环己酮PDO)，2.阻流膜(聚乳酸PLA类)。At present, the materials used in the degradable occluder developed by Shanghai Shape Memory Alloy Material Co., Ltd. mainly include: 1. Braided wire (polydioxanone PDO), 2. Flow blocking membrane (polylactic acid PLA).
PDO封堵器在3个月左右已经失去了力学强度，并且开始降解。而心脏隔膜内皮化需要1-3个月，这就有可能造成封堵器在早期脱落或碎片栓塞等问题。The PDO occluder has lost its mechanical strength and started to degrade in about 3 months. However, it takes 1-3 months for the endothelialization of the cardiac septum, which may cause problems such as early shedding of the occluder or embolization of fragments.
虽然目前动物(动物模型为比格犬)实验结果显示，可降解封堵器植入1个月内皮化即开始，3个月后内皮化完全，6个月封堵器明显降解，12个月封堵器基本降解，2～3年封堵器降解完全。但是，动物的内皮化速度比人体要快，3个月虽然动物心脏内内皮化已经完全，但人体内可能需要更长的时间。若3个月后封堵器的内皮化还未完成，而封堵器力学性能迅速下降，支撑力降低，PDO丝材开始降解。在心脏血流的冲刷下，封堵器丝材断裂，降解碎片脱落，可能引发血栓，导致肺栓塞甚至脑梗。Although the current animal (animal model is a Beagle dog) experiment results show that the endothelialization of the biodegradable occluder begins 1 month after implantation, and the endothelialization is complete after 3 months. The occluder basically degrades, and the occluder degrades completely within 2 to 3 years. However, the speed of endothelialization in animals is faster than that in humans. Although the endothelialization in the heart of animals has been completed within 3 months, it may take longer in humans. If the endothelialization of the occluder has not been completed after 3 months, the mechanical properties of the occluder decline rapidly, the supporting force decreases, and the PDO wire begins to degrade. Under the scouring of the heart's blood flow, the wire material of the occluder breaks, and the degraded fragments fall off, which may cause thrombus, pulmonary embolism or even cerebral infarction.
如何控制以PDO可降解缝合线为丝材编织，以PDLLA为阻流膜的可降解封堵器在体内的降解速率，是一个亟待解决的问题。How to control the degradation rate of the biodegradable occluder with PDO degradable suture as the silk material and PDLLA as the flow blocking membrane in vivo is an urgent problem to be solved.
考虑到材料的生物相容性，可降解性，可编织性，可定型性，形状记忆性等性能，以可降解缝合线PDO作为丝材，编织的可降解封堵器是目前工程技术角度最为理想的制作材料。Considering the biocompatibility, degradability, weavability, shapeability, shape memory and other properties of the material, the degradable suture PDO is used as the filament, and the degradable braided occluder is currently the most advanced engineering technology. Ideal crafting material.
虽然动物实验结果显示PDO可降解封堵器的降解速率与内皮化速度相匹配，但是人体的内皮化速度较动物慢，因此可能存在封堵器已经开始降解而内皮化仍未完全的风险，可能导致封堵器降解碎片被心脏内血流冲刷脱落，引发血栓等。Although the results of animal experiments show that the degradation rate of the PDO degradable occluder matches the endothelialization rate, the endothelialization rate of the human body is slower than that of animals, so there may be a risk that the occluder has begun to degrade but the endothelialization is not yet complete. As a result, the degraded fragments of the occluder are washed away by the blood flow in the heart and cause thrombus.
发明内容Contents of the invention
本发明所要解决的问题是：现有可降解封堵器的降解速度过快的问题。The problem to be solved by the invention is: the degradation speed of the existing degradable occluder is too fast.
为了解决上述问题，本发明提供了一种降解速率可控的可降解封堵器的制备方法，所述可降解封堵器包括丝材和阻流膜，其特征在于，采用以下方法的其中一种或两种：In order to solve the above problems, the present invention provides a method for preparing a degradable occluder with a controllable degradation rate. The degradable occluder includes a silk material and a choke film, and is characterized in that one of the following methods is adopted: one or both:
方法一：在丝材的表面增加生物相容性涂层，阻隔丝材与水接触，延缓其力学性能降低速度和降解速率，使其能够在人体内完全内皮化之后才开始逐步降解；Method 1: Add a biocompatible coating on the surface of the silk material to block the contact between the silk material and water, delay the reduction rate and degradation rate of its mechanical properties, and enable it to gradually degrade after it is completely endothelialized in the human body;
方法二：在丝材和阻流膜的表面引入能促进内皮化速度的基团、肽键、生长因子和药物中的任意一种或几种，使封堵器植入后更快的完成内皮化；Method 2: Introduce any one or more of groups, peptide bonds, growth factors and drugs that can accelerate the speed of endothelialization on the surface of the silk and flow-blocking membrane, so that the endothelialization can be completed faster after the occluder is implanted. change;
当采用两种方法时，先实施方法一，再实施方法二。When using two methods, first implement method one, and then implement method two.
优选地，所述方法一具体为：在丝材和阻流膜的表面浸涂降解周期比可降解封堵器长的可降解涂层。Preferably, the first method specifically includes: dip-coating a degradable coating with a degradation period longer than that of the degradable occluder on the surface of the wire material and the choke membrane.
更优选地，所述可降解涂层采用聚乳酸(生物相容性好，降解速度慢，植入6个月后开始降解，完全降解需要3～5年时间)、聚己内酯或有机硅。一方面，这些高分子材料均具有较好的生物相容性，且降解周期较长，另一方面，在可降解封堵器表面涂覆一层高分子的保护膜，可以使丝材不直接与水分接触，丝材的降解原理主要为水解。同时，这些高分子材料的降解周期长，即使丝材已经开始降解，由于外面包裹着降解周期更长的高分子膜，使其降解产物被包裹着，不能脱落，短时间内也无法进入到血液中，没有引发血栓的风险。最后，在封堵器已经完全内皮化后，封堵器表面的涂层开始降解，使涂层内部的丝材的降解碎片释放，由于封堵器已经被内皮细胞包裹，已不存在降解碎片剥落，引发血栓的风险。More preferably, the degradable coating is made of polylactic acid (good biocompatibility, slow degradation rate, begins to degrade 6 months after implantation, and takes 3 to 5 years for complete degradation), polycaprolactone or silicone . On the one hand, these polymer materials have good biocompatibility, and the degradation cycle is longer; In contact with moisture, the degradation principle of silk is mainly hydrolysis. At the same time, the degradation cycle of these polymer materials is long. Even if the silk material has begun to degrade, because the polymer film with a longer degradation cycle is wrapped outside, the degradation products are wrapped and cannot fall off, and cannot enter the blood in a short time. , there is no risk of blood clots. Finally, after the occluder has been completely endothelialized, the coating on the surface of the occluder begins to degrade, releasing the degraded fragments of the wire inside the coating. Since the occluder has been wrapped by endothelial cells, there is no degraded debris peeling off , causing the risk of thrombosis.
优选地，所述方法二具体为：在丝材和阻流膜的表面修饰或浸涂能促进内皮化速度的生长因子、短肽和蛋白中的任意一种或几种。Preferably, the second method specifically includes: modifying or dip-coating any one or several of growth factors, short peptides and proteins that can accelerate the speed of endothelialization on the surface of the silk and flow-blocking membrane.
更优选地，所述生长因子通过化学方法或物理方法引入到丝材和阻流膜的表面，促进封堵器在缺损部位的快速内皮化；所述化学方法为：通过化学键引入官能团或化学键结合生长因子。More preferably, the growth factor is chemically or physically introduced into the surface of the silk and the flow-blocking membrane to promote rapid endothelialization of the occluder at the defect site; the chemical method is: introduction of functional groups or chemical bonding through chemical bonds growth factor.
进一步地，所述生长因子为EGF、FGF或PDGF。Further, the growth factor is EGF, FGF or PDGF.
更优选地，所述短肽采用细胞外基质功能蛋白的短肽，既能促进内皮细胞的黏附，也能避免直接引入天然细胞外基质成分的缺陷。More preferably, the short peptide is a short peptide of an extracellular matrix functional protein, which can not only promote the adhesion of endothelial cells, but also avoid the defect of directly introducing natural extracellular matrix components.
进一步地，所述短肽为非特异性多肽和特异性多肽中的任意一种或两种；非特异性多肽为RGD或YIGSR，此类多肽均能促进包括内皮细胞在内多种细胞类型的黏附；特异性多肽为REDV、CAG或SVVYGLR，这些多肽可选择性促进内皮细胞的黏附和扩展。应用此类多肽表面修饰，可特异性促进材料的内皮化。联合应用几种多肽或联合特异性多肽与其他一些生物信息分子也许是未来应用多肽修饰促进心血管植入材料内皮化的理想方案。Further, the short peptide is any one or both of a non-specific polypeptide and a specific polypeptide; the non-specific polypeptide is RGD or YIGSR, and such polypeptides can promote the adhesion of various cell types including endothelial cells; The specific peptides are REDV, CAG or SVVYGLR, which selectively promote endothelial cell adhesion and expansion. The application of such peptide surface modification can specifically promote the endothelialization of materials. Combining several peptides or combining specific peptides with some other bioinformatics molecules may be an ideal solution for the future application of peptide modification to promote endothelialization of cardiovascular implant materials.
更优选地，所述蛋白为层粘连蛋白，其通过化学方法或物理方法引入到丝材和阻流膜的表面。层粘连蛋白具有内皮细胞特异性结合位点，能够在材料植入人体后快速内皮化。More preferably, the protein is laminin, which is chemically or physically introduced to the surface of the silk and flow-blocking membrane. Laminin has endothelial cell-specific binding sites and is capable of rapid endothelialization after the material is implanted in the human body.
优选地，所述丝材为PDO丝材，所述阻流膜为PDLLA膜。Preferably, the wire is a PDO wire, and the flow blocking film is a PDLLA film.
采用本发明制备的可降解封堵器使封堵器的降解速度可控，减缓可降解封堵器的降解速度，其应用于心脏隔膜时，能够确保心脏隔膜内皮化后才开始降解，避免了封堵器在早期脱落或碎片栓塞等问题。The degradable occluder prepared by the present invention makes the degradation speed of the occluder controllable and slows down the degradation speed of the degradable occluder. When it is applied to the heart diaphragm, it can ensure that the heart diaphragm begins to degrade after endothelialization, avoiding the Problems such as early shedding of the occluder or embolization of fragments.
附图说明Description of drawings
图1为大鼠体内PCL的分子量随时间的变化数据图表；Fig. 1 is the data chart of the change of the molecular weight of PCL with time in the rat body;
图2为聚左旋乳酸在缓冲溶液中的降解曲线；Fig. 2 is the degradation curve of poly-L-lactic acid in buffer solution;
图3为聚羟基乙酸在缓冲溶液中的降解曲线。Fig. 3 is the degradation curve of polyglycolic acid in buffer solution.
具体实施方式Detailed ways
为使本发明更明显易懂，兹以优选实施例，作详细说明如下。In order to make the present invention more comprehensible, preferred embodiments are described in detail as follows.
实施例1Example 1
将PDO丝材编织，缝合PDLLA阻流膜的可降解封堵器浸润到聚己内酯PCL、左旋聚乳酸PLLA、外消旋聚乳酸PDLLA等溶液中(PCL、PLLA、PDLLA为溶质，氯仿、二氯甲烷、六氟异丙醇为等溶剂)，浸润10min，取出后通风橱内晾干，清洗灭菌包装，手术直接使用。The degradable occluder woven with PDO silk and sutured with PDLLA flow-blocking membrane is infiltrated into polycaprolactone PCL, L-polylactic acid PLLA, racemic polylactic acid PDLLA and other solutions (PCL, PLLA, PDLLA are solutes, chloroform, dichloromethane, hexafluoroisopropanol as solvents), soak for 10 minutes, take it out and dry it in a fume hood, clean and sterilize the package, and use it directly in the operation.
实施例2Example 2
将PDO丝材编织，缝合PDLA阻流膜的可降解封堵器清洗灭菌包装，手术前拆开包装，将封堵器浸润于溶解有EGF、FGF或PDGF等生长因子的无菌生理盐水中，浓度约为1％～5％，浸润时间为3～10min。并使用溶解有生长因子的溶液作为封堵器装在后的排气溶液。The degradable occluder woven with PDO silk and sutured with PDLA choke membrane is cleaned and sterilized, and the package is unpacked before the operation, and the occluder is soaked in sterile saline solution with growth factors such as EGF, FGF or PDGF , the concentration is about 1% to 5%, and the infiltration time is 3 to 10 minutes. And use the solution dissolved with the growth factor as the exhaust solution after the occluder is installed.
实施例3Example 3
将PDO丝材编织，缝合PDLLA阻流膜的可降解封堵器浸润到聚己内酯PCL的溶液中(PCL为溶质，氯仿、二氯甲烷、六氟异丙醇为等溶剂)，浸润10min，取出后通风橱内晾干，清洗灭菌包装。手术前，在手术室内，将封堵器浸润于溶解有促进内皮化的生长因子、多肽、蛋白的无菌生理盐水中，浓度约为1％～5％，浸润时间为3～10min。并使用溶解有生长因子、多肽、蛋白等的溶液作为封堵器装在后的排气溶液。Soak the degradable occluder woven with PDO silk and sutured with PDLLA flow-blocking membrane into the solution of polycaprolactone PCL (PCL is the solute, chloroform, dichloromethane, and hexafluoroisopropanol are the solvents) for 10 minutes , take it out and dry it in the fume hood, clean and sterilize the package. Before the operation, in the operating room, infiltrate the occluder in sterile physiological saline dissolved with growth factors, peptides, and proteins that promote endothelialization, the concentration is about 1% to 5%, and the infiltration time is 3 to 10 minutes. And use a solution dissolved with growth factors, polypeptides, proteins, etc. as the exhaust solution after the occluder is installed.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810237385.1ACN108273142B (en) | 2018-03-21 | 2018-03-21 | Preparation method of degradable occluder with controllable degradation rate |
| Application Number | Priority Date | Filing Date | Title |
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| CN201810237385.1ACN108273142B (en) | 2018-03-21 | 2018-03-21 | Preparation method of degradable occluder with controllable degradation rate |
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| CN108273142Atrue CN108273142A (en) | 2018-07-13 |
| CN108273142B CN108273142B (en) | 2021-01-12 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810237385.1AActiveCN108273142B (en) | 2018-03-21 | 2018-03-21 | Preparation method of degradable occluder with controllable degradation rate |
| Country | Link |
|---|---|
| CN (1) | CN108273142B (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464167A (en)* | 2018-12-11 | 2019-03-15 | 先健科技(深圳)有限公司 | Plugging device and preparation method thereof |
| CN109464168A (en)* | 2018-12-17 | 2019-03-15 | 先健科技(深圳)有限公司 | occluder |
| CN109498074A (en)* | 2019-01-04 | 2019-03-22 | 上海形状记忆合金材料有限公司 | Method Wholly-degradable plugging device dedicated driving means and its connect with plugging device |
| CN113769177A (en)* | 2021-08-26 | 2021-12-10 | 四川大学 | Degradable occluder coating and preparation method thereof |
| CN114533969A (en)* | 2022-01-18 | 2022-05-27 | 深圳市儿童医院 | Preparation method and application of anti-streaming membrane for promoting endothelialization |
| CN115054307A (en)* | 2022-06-30 | 2022-09-16 | 上海微创医疗器械（集团）有限公司 | Occlusion implant and method for producing the same |
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| US20050267523A1 (en)* | 2004-03-03 | 2005-12-01 | Nmt Medical Inc. | Delivery/recovery system for septal occluder |
| CN1736345A (en)* | 2004-08-19 | 2006-02-22 | 深圳市先健科技股份有限公司 | Bioceramic stopper and preparation method thereof |
| CN101061972A (en)* | 2006-04-28 | 2007-10-31 | 解启莲 | Tissue engineering patend ductus arteriosus occluder |
| CN101548916A (en)* | 2009-05-08 | 2009-10-07 | 乐普（北京）医疗器械股份有限公司 | A medical equipment carrying extracellular matrix and its production method |
| CN103110444A (en)* | 2013-01-22 | 2013-05-22 | 陈平根 | Biodegradable fabric body capable of being developed and conveying device |
| CN204016366U (en)* | 2014-06-13 | 2014-12-17 | 上海形状记忆合金材料有限公司 | A kind of degradable stopper |
| CN205251616U (en)* | 2015-11-27 | 2016-05-25 | 先健科技(深圳)有限公司 | Can absorb plugging device |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050267523A1 (en)* | 2004-03-03 | 2005-12-01 | Nmt Medical Inc. | Delivery/recovery system for septal occluder |
| CN1736345A (en)* | 2004-08-19 | 2006-02-22 | 深圳市先健科技股份有限公司 | Bioceramic stopper and preparation method thereof |
| CN101061972A (en)* | 2006-04-28 | 2007-10-31 | 解启莲 | Tissue engineering patend ductus arteriosus occluder |
| CN101548916A (en)* | 2009-05-08 | 2009-10-07 | 乐普（北京）医疗器械股份有限公司 | A medical equipment carrying extracellular matrix and its production method |
| CN103110444A (en)* | 2013-01-22 | 2013-05-22 | 陈平根 | Biodegradable fabric body capable of being developed and conveying device |
| CN204016366U (en)* | 2014-06-13 | 2014-12-17 | 上海形状记忆合金材料有限公司 | A kind of degradable stopper |
| CN205251616U (en)* | 2015-11-27 | 2016-05-25 | 先健科技(深圳)有限公司 | Can absorb plugging device |
| Title |
|---|
| 黄曜等: "《先天性心脏病生物可吸收封堵器的研究现状及展望》", 《中国介入心脏病学杂志》* |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464167A (en)* | 2018-12-11 | 2019-03-15 | 先健科技(深圳)有限公司 | Plugging device and preparation method thereof |
| CN109464168A (en)* | 2018-12-17 | 2019-03-15 | 先健科技(深圳)有限公司 | occluder |
| CN109464168B (en)* | 2018-12-17 | 2020-09-29 | 先健科技(深圳)有限公司 | occluder |
| CN109498074A (en)* | 2019-01-04 | 2019-03-22 | 上海形状记忆合金材料有限公司 | Method Wholly-degradable plugging device dedicated driving means and its connect with plugging device |
| CN113769177A (en)* | 2021-08-26 | 2021-12-10 | 四川大学 | Degradable occluder coating and preparation method thereof |
| CN114533969A (en)* | 2022-01-18 | 2022-05-27 | 深圳市儿童医院 | Preparation method and application of anti-streaming membrane for promoting endothelialization |
| CN115054307A (en)* | 2022-06-30 | 2022-09-16 | 上海微创医疗器械（集团）有限公司 | Occlusion implant and method for producing the same |
| Publication number | Publication date |
|---|---|
| CN108273142B (en) | 2021-01-12 |
| Publication | Publication Date | Title |
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| CN108273142A (en) | A kind of preparation method of the controllable degradable plugging device of degradation rate | |
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