技术领域Technical Field
本发明涉及医用栓塞材料制备技术领域，具体涉及一种显影可生物降解医用聚氨酯泡沫及其制备方法。The invention relates to the technical field of preparation of medical embolic materials, in particular to a developable biodegradable medical polyurethane foam and a preparation method thereof.
背景技术Background Art
在治疗腹主动脉瘤过程中，常出现术后内漏并发症，因此通常会选择介入栓塞治疗微创，降低血液的流经速度和流通量，使得瘤腔体内顺利完成血栓化，常用的栓塞材料有弹簧圈、明胶粉、组织粘合剂、凝血酶和血管塞等，虽然上述材料目前基本已有临床实例，但是依然存在一些不足之处。金属弹簧圈是目前最常用的血管栓塞材料，其具有长期稳定性和较强的支撑性能，弹簧圈的不足在于，介入后在锚定区与支架无法与主动脉壁完全贴合，致密性不佳，可能导致栓塞化不完全，出现内漏等并发症，有资料显示金属弹簧圈成栓率介于80-92%，长期的植入还会导致金属离子析出可能引起过敏、炎症等，并且在实现医学功能后还需要再次手术清除形成的血栓；明胶、凝血酶主要应用于短期栓塞术，优点在于血栓形成快、无毒副作用且代谢时间短，最大程度减轻预后副作用，不足的是无法提供较高的支撑强度，血压高易导致栓塞进入周身循环，影响其他组织或结构，降解速率过快不易控制栓塞功能，因此不满足流速快，血压高的动脉血管的成栓条件。In the process of treating abdominal aortic aneurysm, postoperative endoleak complications often occur. Therefore, minimally invasive interventional embolization is usually chosen to reduce the blood flow rate and circulation volume so that thrombosis can be successfully completed in the aneurysm cavity. Commonly used embolic materials include spring coils, gelatin powder, tissue adhesives, thrombin and vascular plugs. Although the above materials currently have basic clinical examples, there are still some shortcomings. Metal spring coils are currently the most commonly used vascular embolization materials. They have long-term stability and strong supporting performance. The disadvantage of the spring coils is that after intervention, the anchoring area and the stent cannot be completely fitted with the aortic wall, and the density is poor, which may lead to incomplete embolization and complications such as endoleak. Data show that the thrombosis rate of metal spring coils is between 80-92%. Long-term implantation will also lead to the precipitation of metal ions, which may cause allergies, inflammation, etc., and after achieving the medical function, another surgery is required to remove the formed thrombus; gelatin and thrombin are mainly used in short-term embolization. The advantages are fast thrombosis, no toxic side effects and short metabolism time, which minimizes the prognosis and side effects. The disadvantage is that they cannot provide high support strength. High blood pressure can easily cause embolism to enter the systemic circulation and affect other tissues or structures. The degradation rate is too fast and it is difficult to control the embolization function. Therefore, it does not meet the thrombosis conditions of arteries with fast flow rate and high blood pressure.
同时因植入的泡沫是聚合物材料，以碳氢结构为主，在X-光下几乎不显影，无法判断材料植入后真实的状态以及是否发挥医学作用，因此引入显影剂以便植入后的材料显影。采用简单的共混法所制备的显影材料，因为不存在化学键合作用而导致显影剂主动释放，且可降解的材料还会加速释放的速度，一旦释放完毕后期显影功能即丢失，考虑显影材料的主动释放以及材料在基材中的分散性，因此显影剂的添加比例通常较高，甚至超过50%。如果直接采用共聚法，碘化合物由于高反应性，容易发生化学反应而失效，也会失去显影功能，同时共聚还会导致泡沫的物理性能下降。目前市面上已有的产品为水凝胶类微球，这种栓塞产品时效性短，无法作长期植入显影观察。At the same time, because the implanted foam is a polymer material, which is mainly composed of a hydrocarbon structure and hardly develops under X-rays, it is impossible to judge the real state of the material after implantation and whether it plays a medical role. Therefore, a developer is introduced to develop the material after implantation. The developer prepared by a simple blending method is actively released because there is no chemical bonding, and the degradable material will also accelerate the release rate. Once the release is completed, the later development function is lost. Considering the active release of the developer material and the dispersibility of the material in the substrate, the addition ratio of the developer is usually high, even exceeding 50%. If the copolymerization method is directly used, the iodine compound is highly reactive and easily chemically reacted and loses its effectiveness, and the development function will also be lost. At the same time, copolymerization will also cause the physical properties of the foam to decrease. The products currently available on the market are hydrogel microspheres. This type of embolization product has a short timeliness and cannot be implanted for long-term development observation.
因此，开发出一种高致密性、高支撑强度、降解周期可控且显影的栓塞材料成为未来的一种趋势。Therefore, developing an embolic material with high density, high support strength, controllable degradation cycle and imaging has become a future trend.
发明内容Summary of the invention
为了解决上述技术问题，本发明的目的是提供一种显影可生物降解医用聚氨酯泡沫及其制备方法，以解决现有技术中栓塞材料性能不佳的问题。In order to solve the above technical problems, the purpose of the present invention is to provide a developable biodegradable medical polyurethane foam and a preparation method thereof, so as to solve the problem of poor performance of embolic materials in the prior art.
本发明解决上述技术问题的技术方案如下：提供一种显影可生物降解医用聚氨酯泡沫及其制备方法，包括以下步骤：The technical solution of the present invention to solve the above technical problems is as follows: Provide a developable biodegradable medical polyurethane foam and a preparation method thereof, comprising the following steps:
（1）将显影材料和异氰酸酯混合均匀，然后加入多元醇和催化剂，搅拌均匀，再加入分散剂和水，搅拌形成稳定的悬浮体系；(1) Mix the developer and isocyanate evenly, then add the polyol and catalyst, stir evenly, then add the dispersant and water, and stir to form a stable suspension system;
（2）将步骤（1）得到的悬浮体系第一次聚合，然后第二次聚合，冷却，再离心、清洗和干燥，制得显影聚氨酯微球；(2) polymerizing the suspension system obtained in step (1) for the first time, then polymerizing it for the second time, cooling it, centrifuging it, washing it and drying it to obtain developed polyurethane microspheres;
（3）将步骤（2）制得的显影聚氨酯微球、异氰酸酯和部分多元醇混合，搅拌进行预聚合，然后加入剩余多元醇、催化剂、硅油、发泡剂和水，将得到的混合物进行聚合发泡和热处理，得到中间体；(3) mixing the developed polyurethane microspheres obtained in step (2), isocyanate and part of the polyol, stirring for prepolymerization, then adding the remaining polyol, catalyst, silicone oil, foaming agent and water, polymerizing and foaming the obtained mixture and heat treating it to obtain an intermediate;
（4）将步骤（3）得到的中间体采用制孔剂浸泡进行制孔，然后清洗和干燥，制得显影可生物降解医用聚氨酯泡沫。(4) The intermediate obtained in step (3) is soaked in a pore-forming agent to form pores, and then washed and dried to obtain a developable biodegradable medical polyurethane foam.
在上述技术方案的基础上，本发明还可以做如下改进：On the basis of the above technical solution, the present invention can also be improved as follows:
进一步，步骤（1）中，显影材料、异氰酸酯、多元醇、催化剂、分散剂和水的质量比为1-30：5-70：5-70：0.1-5：0.2-2：100。Furthermore, in step (1), the mass ratio of the developing material, isocyanate, polyol, catalyst, dispersant and water is 1-30:5-70:5-70:0.1-5:0.2-2:100.
采用上述进一步技术方案的有益效果为：上述比例能够形成稳定的包含有显影材料的交联型聚氨酯微球，且显影强弱可通过更改比例实现调控。The beneficial effect of adopting the above further technical solution is that the above ratio can form stable cross-linked polyurethane microspheres containing developing materials, and the developing strength can be controlled by changing the ratio.
进一步，步骤（1）中，显影材料、异氰酸酯、多元醇、催化剂、分散剂和水的质量比为8：55：27：1.8：1.5：100。Furthermore, in step (1), the mass ratio of the developing material, isocyanate, polyol, catalyst, dispersant and water is 8:55:27:1.8:1.5:100.
进一步，步骤（1）中，显影材料为钽纳米颗粒、碱式碳酸铋、氯氧化铋、氧化铋、硫酸钡或钨。Furthermore, in step (1), the developing material is tantalum nanoparticles, bismuth basic carbonate, bismuth oxychloride, bismuth oxide, barium sulfate or tungsten.
进一步，步骤（1）中，异氰酸酯为六亚甲基二异氰酸酯、三甲基六亚甲基二异氰酸酯、异氟尔酮二异氰酸酯、氢化苯二亚甲基二异氰酸酯、赖氨酸乙酯二异氰酸酯、甲苯二异氰酸酯和亚甲基二苯基二异氰酸酯中至少一种。Furthermore, in step (1), the isocyanate is at least one of hexamethylene diisocyanate, trimethyl hexamethylene diisocyanate, isophorone diisocyanate, hydrogenated xylylene diisocyanate, ethyl lysine diisocyanate, toluene diisocyanate and methylene diphenyl diisocyanate.
进一步，步骤（1）中，多元醇为聚己内酯二元醇、聚乳酸二元醇、聚乙醇酸二元醇、聚己内酯三元醇、聚乳酸三元醇、聚乙醇酸三元醇、聚己内酯四元醇、聚乳酸四元醇、聚乙醇酸四元醇、聚碳酸酯二元醇、聚乙二醇、聚四氢呋喃二元醇、聚六亚甲基醚二元醇、丁二醇、丙二醇、三乙醇胺、羟丙基乙二胺、甘油、季戊四醇、三羟甲基乙烷和三(羟甲基)氨基甲烷中至少一种。Furthermore, in step (1), the polyol is at least one of polycaprolactone diol, polylactic acid diol, polyglycolic acid diol, polycaprolactone triol, polylactic acid triol, polyglycolic acid triol, polycaprolactone tetraol, polylactic acid tetraol, polyglycolic acid tetraol, polycarbonate diol, polyethylene glycol, polytetrahydrofuran diol, polyhexamethylene ether diol, butanediol, propylene glycol, triethanolamine, hydroxypropyl ethylenediamine, glycerol, pentaerythritol, trimethylolethane and tris(hydroxymethyl)aminomethane.
进一步，步骤（1）中，催化剂为有机金属催化剂。Furthermore, in step (1), the catalyst is an organic metal catalyst.
进一步，步骤（1）中，催化剂为有机锡类催化剂或有机铋类催化剂。Furthermore, in step (1), the catalyst is an organotin catalyst or an organobismuth catalyst.
进一步，有机锡类催化剂为辛酸亚锡、二月桂酸二丁基锡、二乙酸二丁基锡和二(十二烷基硫)二丁基锡中至少一种。Furthermore, the organotin catalyst is at least one of stannous octoate, dibutyltin dilaurate, dibutyltin diacetate and dibutyltin didodecylsulfide.
进一步，有机铋类催化剂为月桂酸铋、异辛酸铋和新癸酸铋中至少一种。Furthermore, the organic bismuth catalyst is at least one of bismuth laurate, bismuth isooctanoate and bismuth neodecanoate.
进一步，步骤（1）中，分散剂为纤维素、聚乙烯吡咯烷酮，聚乙烯醇和羟基改性纤维素中至少一种。Furthermore, in step (1), the dispersant is at least one of cellulose, polyvinyl pyrrolidone, polyvinyl alcohol and hydroxy-modified cellulose.
进一步，步骤（1）中，形成稳定的悬浮体系时的搅拌速度为500-2000rpm。Furthermore, in step (1), the stirring speed when forming a stable suspension system is 500-2000 rpm.
进一步，步骤（2）中，于40-60℃条件下聚合2.5-3.5h，完成第一次聚合过程。Furthermore, in step (2), the polymerization is carried out at 40-60° C. for 2.5-3.5 hours to complete the first polymerization process.
进一步，步骤（2）中，于50℃条件下聚合3h，完成第一次聚合过程。Furthermore, in step (2), polymerization is carried out at 50° C. for 3 hours to complete the first polymerization process.
进一步，步骤（2）中，于75-85℃条件下聚合7-9h，完成第二次聚合过程。Furthermore, in step (2), the polymerization is carried out at 75-85° C. for 7-9 hours to complete the second polymerization process.
进一步，步骤（2）中，于80℃条件下聚合8h，完成第二次聚合过程。Furthermore, in step (2), polymerization is carried out at 80° C. for 8 hours to complete the second polymerization process.
进一步，步骤（2）中，重复离心和清洗，然后再干燥。Furthermore, in step (2), centrifugation and washing are repeated, and then drying is performed.
进一步，步骤（3）中，显影聚氨酯微球、异氰酸酯、多元醇、催化剂、硅油、发泡剂和水的质量比为1-30：30-80：10-80：0.1-5：1-15：0.1-15：0.5-5。Furthermore, in step (3), the mass ratio of the developed polyurethane microspheres, isocyanate, polyol, catalyst, silicone oil, foaming agent and water is 1-30:30-80:10-80:0.1-5:1-15:0.1-15:0.5-5.
进一步，步骤（3）中，显影聚氨酯微球、异氰酸酯、多元醇、催化剂、硅油、发泡剂和水的质量比为10：40：42：1.3：4.1：0.3：2.3。Furthermore, in step (3), the mass ratio of the developed polyurethane microspheres, isocyanate, polyol, catalyst, silicone oil, foaming agent and water is 10:40:42:1.3:4.1:0.3:2.3.
进一步，步骤（3）中，部分多元醇和剩余多元醇的质量比为70：30。Furthermore, in step (3), the mass ratio of the partial polyol to the remaining polyol is 70:30.
进一步，步骤（3）中，异氰酸酯为六亚甲基二异氰酸酯、三甲基六亚甲基二异氰酸酯、异氟尔酮二异氰酸酯、氢化苯二亚甲基二异氰酸酯、赖氨酸乙酯二异氰酸酯、甲苯二异氰酸酯和亚甲基二苯基二异氰酸酯中至少一种。Furthermore, in step (3), the isocyanate is at least one of hexamethylene diisocyanate, trimethyl hexamethylene diisocyanate, isophorone diisocyanate, hydrogenated xylylene diisocyanate, ethyl lysine diisocyanate, toluene diisocyanate and methylene diphenyl diisocyanate.
进一步，步骤（3）中，多元醇为聚己内酯二元醇、聚乳酸二元醇、聚乙醇酸二元醇、聚己内酯三元醇、聚乳酸三元醇、聚乙醇酸三元醇、聚己内酯四元醇、聚乳酸四元醇、聚乙醇酸四元醇、聚碳酸酯二元醇、聚乙二醇、聚四氢呋喃二元醇、聚六亚甲基醚二元醇、丁二醇、丙二醇、三乙醇胺、羟丙基乙二胺、甘油、季戊四醇、三羟甲基乙烷和三(羟甲基)氨基甲烷中至少一种。Furthermore, in step (3), the polyol is at least one of polycaprolactone diol, polylactic acid diol, polyglycolic acid diol, polycaprolactone triol, polylactic acid triol, polyglycolic acid triol, polycaprolactone tetraol, polylactic acid tetraol, polyglycolic acid tetraol, polycarbonate diol, polyethylene glycol, polytetrahydrofuran diol, polyhexamethylene ether diol, butanediol, propylene glycol, triethanolamine, hydroxypropyl ethylenediamine, glycerol, pentaerythritol, trimethylolethane and tris(hydroxymethyl)aminomethane.
进一步，步骤（3）中，催化剂为有机金属催化剂。Furthermore, in step (3), the catalyst is an organic metal catalyst.
进一步，步骤（3）中，催化剂为有机锡类催化剂或有机铋类催化剂。Furthermore, in step (3), the catalyst is an organotin catalyst or an organobismuth catalyst.
进一步，有机锡类催化剂为辛酸亚锡、二月桂酸二丁基锡、二乙酸二丁基锡和二(十二烷基硫)二丁基锡中至少一种。Furthermore, the organotin catalyst is at least one of stannous octoate, dibutyltin dilaurate, dibutyltin diacetate and dibutyltin didodecylsulfide.
进一步，有机铋类催化剂为月桂酸铋、异辛酸铋和新癸酸铋中至少一种。Furthermore, the organic bismuth catalyst is at least one of bismuth laurate, bismuth isooctanoate and bismuth neodecanoate.
进一步，步骤（3）中，发泡剂为二氯甲烷、三氯甲烷和丙酮中至少一种。Furthermore, in step (3), the foaming agent is at least one of dichloromethane, chloroform and acetone.
进一步，步骤（3）中，搅拌24h进行预聚合。Furthermore, in step (3), the prepolymerization is carried out by stirring for 24 hours.
进一步，步骤（3）中，搅拌22-26h进行预聚合。Furthermore, in step (3), the prepolymerization is carried out by stirring for 22-26 hours.
进一步，步骤（3）中，75-85℃条件下，聚合发泡7.5-8.5h和热处理1.8-2.2d。Furthermore, in step (3), the polymerization and foaming are carried out at 75-85°C for 7.5-8.5 hours and the heat treatment is carried out for 1.8-2.2 days.
进一步，步骤（3）中，于80℃条件下，聚合发泡8h和热处理2d。Furthermore, in step (3), the polymerization and foaming are carried out at 80° C. for 8 h and the heat treatment is carried out for 2 d.
进一步，步骤（4）中，制孔剂为体积比为1：4-6：3-5的氢氧化钠、异丙醇和水的混合物。Furthermore, in step (4), the pore-forming agent is a mixture of sodium hydroxide, isopropanol and water in a volume ratio of 1:4-6:3-5.
进一步，步骤（4）中，制孔剂为体积比为1：5：4的氢氧化钠、异丙醇和水的混合物。Furthermore, in step (4), the pore-forming agent is a mixture of sodium hydroxide, isopropanol and water in a volume ratio of 1:5:4.
进一步，步骤（4）中，挤压浸泡4-6min，完成制孔过程。Furthermore, in step (4), the extrusion and soaking are performed for 4-6 minutes to complete the hole making process.
进一步，步骤（4）中，挤压浸泡5min。Further, in step (4), the mixture is squeezed and soaked for 5 minutes.
本发明还提供一种显影可生物降解医用聚氨酯泡沫，采用上述方法制得。The invention also provides a developable biodegradable medical polyurethane foam, which is prepared by the method.
本发明还提供上述显影可生物降解医用聚氨酯泡沫在血管栓塞材料制备方面的应用。The present invention also provides application of the above-mentioned developable biodegradable medical polyurethane foam in the preparation of vascular embolization materials.
本发明具有以下有益效果：The present invention has the following beneficial effects:
1、本发明将显影剂和聚氨酯先制备成核壳结构的聚氨酯显影微球，再将微球添加至聚氨酯预聚体中，共发泡制备出具有显影功能的聚氨酯泡沫材料。本发明的泡沫材料在微创介入中，能显影跟踪以便确认材料是否到达目标位置，植入后能快速形成血栓完成封堵作用，可持续显影反应出材料真实状态和封堵效果，同时方便了预后的复查，随后被机体降解无毒代谢，达到了术中确认、术后跟踪、预后诊断的目的，适用于心血管的封堵填充材料。1. The present invention prepares a developer and polyurethane into polyurethane developing microspheres with a core-shell structure, and then adds the microspheres to a polyurethane prepolymer, and co-foams to prepare a polyurethane foam material with a developing function. The foam material of the present invention can be developed and tracked in minimally invasive intervention to confirm whether the material has reached the target position, can quickly form a thrombus after implantation to complete the blocking effect, can continuously develop to reflect the true state and blocking effect of the material, and facilitates the review of the prognosis. It is then degraded and metabolized by the body without toxicity, achieving the purpose of intraoperative confirmation, postoperative tracking, and prognosis diagnosis, and is suitable for cardiovascular blocking filling materials.
2、本发明利用聚合物微球包裹无机颗粒，以及原位共混的方式，通过两步法有效避免了无机颗粒对聚氨酯发泡的影响，包括密度、孔径和孔隙率，最大程度减小对泡沫自膨胀性能的影响。2. The present invention utilizes polymer microspheres to wrap inorganic particles and in-situ blending to effectively avoid the influence of inorganic particles on polyurethane foaming, including density, pore size and porosity, through a two-step method, thereby minimizing the influence on the self-expansion performance of the foam.
3、本发明的方法同样适用于其他使用聚合物材料作为植入体代替金属的例子，且显影剂可根据植入部位和目的更换。3. The method of the present invention is also applicable to other examples of using polymer materials as implants instead of metals, and the imaging agent can be replaced according to the implantation site and purpose.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
图1为实施例1制得的聚氨酯泡沫；Fig. 1 is the polyurethane foam obtained in Example 1;
图2为对比例1的不显影聚氨酯泡沫；FIG2 is a non-developable polyurethane foam of Comparative Example 1;
图3为对比例2的显影聚氨酯泡沫；FIG3 is a developing polyurethane foam of Comparative Example 2;
图4为实施例1制得的聚氨酯泡沫在X光下的可见性。FIG. 4 shows the visibility of the polyurethane foam prepared in Example 1 under X-ray.
具体实施方式DETAILED DESCRIPTION
以下结合附图对本发明的原理和特征进行描述，所举实例只用于解释本发明，并非用于限定本发明的范围。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市售购买获得的常规产品。The principles and features of the present invention are described below in conjunction with the accompanying drawings. The examples are only used to explain the present invention and are not used to limit the scope of the present invention. If specific conditions are not specified in the embodiments, they are carried out according to normal conditions or conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.
实施例1：Embodiment 1:
一种显影可生物降解医用聚氨酯泡沫，其制备方法包括以下步骤：A developable biodegradable medical polyurethane foam, the preparation method of which comprises the following steps:
（1）将显影材料（钽纳米颗粒）和异氰酸酯（六亚甲基二异氰酸酯）混合均匀，然后加入多元醇（质量比为25：2的乳酸三元醇和三乙醇胺）和催化剂（辛酸亚锡），搅拌均匀，再加入分散剂（纤维素）和水，1000rpm速度高速搅拌形成稳定的悬浮体系；(1) Mix the developer (tantalum nanoparticles) and isocyanate (hexamethylene diisocyanate) evenly, then add polyol (lactic acid triol and triethanolamine in a mass ratio of 25:2) and catalyst (stannous octoate), stir evenly, then add dispersant (cellulose) and water, and stir at a high speed of 1000 rpm to form a stable suspension system;
其中，显影材料、异氰酸酯、多元醇、催化剂、分散剂和水的质量比为8：55：27：1.8：1.5：100；The mass ratio of the developing material, isocyanate, polyol, catalyst, dispersant and water is 8:55:27:1.8:1.5:100;
（2）将步骤（1）得到的悬浮体系于50℃条件下第一次聚合3h，于80℃条件下第二次聚合8h，冷却，离心固相分离得到固体相，清洗，重复离心和清洗，得到的固相物真空干燥，制得显影聚氨酯微球；(2) polymerizing the suspension system obtained in step (1) at 50° C. for 3 h for the first time and at 80° C. for the second time for 8 h, cooling, centrifuging and solid phase separation to obtain a solid phase, washing, repeating centrifugation and washing, and vacuum drying the obtained solid phase to obtain developed polyurethane microspheres;
（3）将步骤（2）制得的显影聚氨酯微球、异氰酸酯（六亚甲基二异氰酸酯）和部分多元醇（质量比为40：2的乳酸三元醇和三乙醇胺）混合，搅拌24h进行预聚合，然后快速加入剩余多元醇（部分多元醇和剩余多元醇的质量比为70：30）、催化剂（月桂酸铋）、硅油、发泡剂（二氯甲烷）和水，混合后转移至80℃烘箱聚合发泡8h，并持续热处理2d，得到中间体；(3) The developed polyurethane microspheres prepared in step (2), isocyanate (hexamethylene diisocyanate) and part of the polyol (lactic acid triol and triethanolamine in a mass ratio of 40:2) are mixed and stirred for 24 hours for prepolymerization, and then the remaining polyol (the mass ratio of part of the polyol to the remaining polyol is 70:30), catalyst (bismuth laurate), silicone oil, foaming agent (dichloromethane) and water are quickly added, and after mixing, the mixture is transferred to an oven at 80°C for polymerization and foaming for 8 hours, and the heat treatment is continued for 2 days to obtain an intermediate;
其中，显影聚氨酯微球、异氰酸酯、多元醇、催化剂、硅油、发泡剂和水的质量比为10：40：42：1.3：4.1：0.3：2.3；The mass ratio of the developing polyurethane microspheres, isocyanate, polyol, catalyst, silicone oil, foaming agent and water is 10:40:42:1.3:4.1:0.3:2.3;
（4）将步骤（3）得到的中间体采用制孔剂（体积比为1：5：4的氢氧化钠、异丙醇和水的混合物）挤压浸泡5min进行制孔，然后依次采用水、异丙醇、去离子水清洗，干燥，制得显影可生物降解医用聚氨酯泡沫。(4) The intermediate obtained in step (3) is squeezed and soaked in a pore-forming agent (a mixture of sodium hydroxide, isopropanol and water in a volume ratio of 1:5:4) for 5 minutes to form pores, and then washed with water, isopropanol and deionized water in sequence, and dried to obtain a developable biodegradable medical polyurethane foam.
实施例2：Embodiment 2:
一种显影可生物降解医用聚氨酯泡沫，其制备方法包括以下步骤：A developable biodegradable medical polyurethane foam, the preparation method of which comprises the following steps:
（1）将显影材料（碱式碳酸铋）和异氰酸酯（三甲基六亚甲基二异氰酸酯）混合均匀，然后加入多元醇（聚己内酯二元醇）和催化剂（新癸酸铋），搅拌均匀，再加入分散剂（纤维素）和水，500rpm度高速搅拌形成稳定的悬浮体系；(1) Mix the developer (bismuth basic carbonate) and isocyanate (trimethylhexamethylene diisocyanate) evenly, then add the polyol (polycaprolactone diol) and catalyst (bismuth neodecanoate), stir evenly, then add the dispersant (cellulose) and water, and stir at 500 rpm to form a stable suspension system;
其中，显影材料、异氰酸酯、多元醇、催化剂、分散剂和水的质量比为1：5：5：0.1：0.2：100；The mass ratio of the developing material, isocyanate, polyol, catalyst, dispersant and water is 1:5:5:0.1:0.2:100;
（2）将步骤（1）得到的悬浮体系于60℃条件下第一次聚合2.5h，于85℃条件下第二次聚合7h，冷却，离心固相分离得到固体相，清洗，重复离心和清洗，得到的固相物真空干燥，制得显影聚氨酯微球；(2) polymerizing the suspension system obtained in step (1) at 60° C. for a first time for 2.5 h and at 85° C. for a second time for 7 h, cooling, centrifuging and separating the solid phase to obtain a solid phase, washing, repeating the centrifugation and washing, and vacuum drying the obtained solid phase to obtain developed polyurethane microspheres;
（3）将步骤（2）制得的显影聚氨酯微球、异氰酸酯（三甲基六亚甲基二异氰酸酯）和部分多元醇（聚己内酯二元醇）混合，搅拌22h进行预聚合，然后快速加入剩余多元醇（部分多元醇和剩余多元醇的质量比为70：30）、催化剂（二月桂酸二丁基锡）硅油、发泡剂（二氯甲烷）和水，混合后转移至75℃烘箱聚合发泡8.5h，并持续热处理2.2d，得到中间体；(3) The developed polyurethane microspheres prepared in step (2), isocyanate (trimethylhexamethylene diisocyanate) and part of the polyol (polycaprolactone diol) are mixed and stirred for 22 hours for prepolymerization, and then the remaining polyol (the mass ratio of the part of the polyol to the remaining polyol is 70:30), catalyst (dibutyltin dilaurate), silicone oil, foaming agent (dichloromethane) and water are quickly added, and after mixing, the mixture is transferred to a 75°C oven for polymerization and foaming for 8.5 hours, and the heat treatment is continued for 2.2 days to obtain an intermediate;
其中，显影聚氨酯微球、异氰酸酯、多元醇、催化剂、硅油、发泡剂和水的质量比为1：30：10：0.1：1：0.1：0.5；The mass ratio of the developing polyurethane microspheres, isocyanate, polyol, catalyst, silicone oil, foaming agent and water is 1:30:10:0.1:1:0.1:0.5;
（4）将步骤（3）得到的中间体采用制孔剂（体积比为1：4：3的氢氧化钠、异丙醇和水的混合物）挤压浸泡4min进行制孔，然后依次采用水、异丙醇、去离子水清洗，干燥，制得显影可生物降解医用聚氨酯泡沫。(4) The intermediate obtained in step (3) is squeezed and soaked in a pore-forming agent (a mixture of sodium hydroxide, isopropanol and water in a volume ratio of 1:4:3) for 4 minutes to form pores, and then washed with water, isopropanol and deionized water in sequence, and dried to obtain a developable biodegradable medical polyurethane foam.
实施例3：Embodiment 3:
一种显影可生物降解医用聚氨酯泡沫，其制备方法包括以下步骤：A developable biodegradable medical polyurethane foam, the preparation method of which comprises the following steps:
（1）将显影材料（氯氧化铋）和异氰酸酯（亚甲基二苯基二异氰酸酯）混合均匀，然后加入多元醇（聚乙二醇）和催化剂（二(十二烷基硫)二丁基锡），搅拌均匀，再加入分散剂（纤维素）和水，2000rpm速度高速搅拌形成稳定的悬浮体系；(1) Mix the developer (bismuth oxychloride) and isocyanate (methylene diphenyl diisocyanate) evenly, then add the polyol (polyethylene glycol) and the catalyst (dibutyltin(didodecylsulfide)), stir evenly, then add the dispersant (cellulose) and water, and stir at a high speed of 2000 rpm to form a stable suspension system;
其中，显影材料、异氰酸酯、多元醇、催化剂、分散剂和水的质量比为30：70：70：5：2：100；The mass ratio of the developing material, isocyanate, polyol, catalyst, dispersant and water is 30:70:70:5:2:100;
（2）将步骤（1）得到的悬浮体系于50℃条件下第一次聚合3h，于80℃条件下第二次聚合8h，冷却，离心固相分离得到固体相，清洗，重复离心和清洗，得到的固相物真空干燥，制得显影聚氨酯微球；(2) polymerizing the suspension system obtained in step (1) at 50° C. for 3 h for the first time and at 80° C. for the second time for 8 h, cooling, centrifuging and solid phase separation to obtain a solid phase, washing, repeating centrifugation and washing, and vacuum drying the obtained solid phase to obtain developed polyurethane microspheres;
（3）将步骤（2）制得的显影聚氨酯微球、异氰酸酯（亚甲基二苯基二异氰酸酯）和部分多元醇（聚乙二醇）混合，搅拌26h进行预聚合，然后快速加入剩余多元醇（部分多元醇和剩余多元醇的质量比为70：30）、催化剂（二乙酸二丁基锡）硅油、发泡剂（二氯甲烷）和水，混合后转移至85℃烘箱聚合发泡7.5h，并持续热处理1.8d，得到中间体；(3) The developed polyurethane microspheres prepared in step (2), isocyanate (methylene diphenyl diisocyanate) and part of the polyol (polyethylene glycol) are mixed and stirred for 26 hours for prepolymerization, and then the remaining polyol (the mass ratio of the part of the polyol to the remaining polyol is 70:30), catalyst (dibutyltin diacetate), silicone oil, foaming agent (dichloromethane) and water are quickly added, and after mixing, the mixture is transferred to an oven at 85°C for polymerization and foaming for 7.5 hours, and the heat treatment is continued for 1.8 days to obtain an intermediate;
其中，显影聚氨酯微球、异氰酸酯、多元醇、催化剂、硅油、发泡剂和水的质量比为30：80：80：5：15：15：5；The mass ratio of the developing polyurethane microspheres, isocyanate, polyol, catalyst, silicone oil, foaming agent and water is 30:80:80:5:15:15:5;
（4）将步骤（3）得到的中间体采用制孔剂（体积比为1：6：5的氢氧化钠、异丙醇和水的混合物）挤压浸泡6min进行制孔，然后依次采用水、异丙醇、去离子水清洗，干燥，制得显影可生物降解医用聚氨酯泡沫。(4) The intermediate obtained in step (3) is squeezed and soaked in a pore-forming agent (a mixture of sodium hydroxide, isopropanol and water in a volume ratio of 1:6:5) for 6 minutes to form pores, and then washed with water, isopropanol and deionized water in sequence, and dried to obtain a developable biodegradable medical polyurethane foam.
对比例1：Comparative Example 1:
一种不显影可生物降解医用聚氨酯泡沫，其制备方法包括以下步骤：A non-developable biodegradable medical polyurethane foam, the preparation method of which comprises the following steps:
不含步骤（1）-（2），步骤（3）中不添加显影微球，其余同实施例1。Steps (1) and (2) are not included, and developing microspheres are not added in step (3). The rest is the same as in Example 1.
对比例2：Comparative Example 2:
一种显影可生物降解医用聚氨酯泡沫，其制备方法包括以下步骤：A developable biodegradable medical polyurethane foam, the preparation method of which comprises the following steps:
不含步骤（1）-（2），直接将显影材料加入步骤（3），进行泡沫制备，其余同实施例1。Without steps (1) and (2), the developer material is directly added to step (3) to prepare the foam, and the rest is the same as in Example 1.
试验例Test example
一、将实施例1和对比例1-2聚氨酯泡沫的进行ETM检测，结果见图1-3。1. The polyurethane foams of Example 1 and Comparative Examples 1-2 were subjected to ETM testing, and the results are shown in Figures 1-3.
由图1-3可知，本发明的添加显影微球的聚氨酯泡沫与对比例1的不显影聚氨酯泡沫孔径以及分布基本一致，而对比例2直接添加无机颗粒的聚氨酯泡沫则孔径分布不均匀，且孔径缩小明显。As shown in Figures 1-3, the pore size and distribution of the polyurethane foam with developing microspheres added in the present invention are basically consistent with those of the non-developing polyurethane foam in Comparative Example 1, while the pore size distribution of the polyurethane foam with inorganic particles directly added in Comparative Example 2 is uneven and the pore size is significantly reduced.
二、将实施例1制得的聚氨酯泡沫在X光下进行显影检测，具体检测方法为Micro-CT。结果见图4。2. The polyurethane foam obtained in Example 1 was developed and tested under X-ray, and the specific testing method was Micro-CT. The results are shown in FIG4 .
由图4可知，本申请聚氨酯泡沫具有X光可见性。As can be seen from FIG. 4 , the polyurethane foam of the present application has X-ray visibility.
三、将实施例1和对比例1-2聚氨酯泡沫的进性能检测，结果见表1。3. The performance of the polyurethane foams of Example 1 and Comparative Examples 1-2 was tested. The results are shown in Table 1.
表1性能参数Table 1 Performance parameters
由表1可知，本发明添加显影微球之后，与对比例1一步法制备的不显影泡沫相比，泡沫的孔径和力学性能相差不大，说明本发明显影微球不会明显地造成泡沫的性能丢失；而对比例2采用直接添加无机显影材料则会影响发泡过程，严重导致泡沫孔径分布不均匀，且对泡沫密度和力学产生了显著的影响，限制了泡沫的应用。As can be seen from Table 1, after adding the developer microspheres in the present invention, the pore size and mechanical properties of the foam are similar to those of the non-developer foam prepared by the one-step method in Comparative Example 1, indicating that the developer microspheres in the present invention will not significantly cause the performance loss of the foam; while in Comparative Example 2, directly adding the inorganic developer material will affect the foaming process, seriously leading to uneven pore size distribution of the foam, and having a significant impact on the foam density and mechanics, limiting the application of the foam.
以上所述仅为本发明的较佳实施例，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
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| CN202411132779.2ACN118652466B (en) | 2024-08-19 | 2024-08-19 | A kind of developing biodegradable medical polyurethane foam and preparation method thereof |
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