CN105999435A - 显影型可降解修复尿道支架 - Google Patents
显影型可降解修复尿道支架 Download PDFInfo
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- CN105999435A CN105999435A CN201610345148.8A CN201610345148A CN105999435A CN 105999435 A CN105999435 A CN 105999435A CN 201610345148 A CN201610345148 A CN 201610345148A CN 105999435 A CN105999435 A CN 105999435A
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- chitosan
- degradable
- developing agent
- urethra
- chitin
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Abstract
本发明涉及一种显影型可降解修复尿道支架，组分包括：50～100重量份可降解医用材料A、0.1～50重量份愈合修复材料B、0.001～0.05重量份显影剂C、0.001～0.05重量份抗高尿酸药物D、0.001～0.05重量份维生素，具有很好的生物相容性，可快捷地判断植入材料的形态和位置，降解时间可控，在复杂的尿道重建过程中，起到减压支撑、引流、利于尿道愈合，便于观察以及术后尿道造影等作用。
Description
技术领域
本发明属于生物医用材料领域，涉及显影型可降解修复尿道支架。
背景技术
介入放射学是放射学领域的一个新的分支学科，它的许多技术都是来源于外科手术，被放射学家所采用和改良的。
介入疗法来自于介入放射学，介于外科、内科治疗之间的新兴治疗方法，利用X线透视、CT定位、B型超声仪等医疗影像设备做导向，将特制的导管或器械经人体动脉、静脉、消化系统的自然管道、尿道或手术后的引流管道抵达体内病变区域，取得组织细胞、细菌或生化方面的资料，也可以进行造影摄片获得影像学资料，从而达到诊断疾病的目的，同时也可进行各种特殊的治疗。目前，导管或器械已经被“介入”到人体几乎所有的血管分支、消化道和其它特定部位，运用于疾病的治疗。
介入治疗包括血管内介入和非血管介入治疗，其中用于胆管，气管和食管等官腔的介入治疗支架属于非血管介入治疗。
在胆管，气管和食管等官腔的介入治疗中实际应用最多的是金属支架。这种类型的支架在植入完成以后将永久存留在人体内，永久性金属支架会削弱血管的磁共振成像或是电子计算机断层扫描影像，干扰外科血运重建，阻碍侧枝循环的形成，抑制血管正性重塑。
可降解高分子材料制备介入支架具有很多优点：(1)良好的生物相容性，在体内降解，避免二次手术；(2)即使意外滑落也会慢慢降解排出体外，不会造成医疗事故；(3)在力学性能上满足人体各种管道扩张的要求，可调节力学强度，提高舒适感；(4)可容易通过物理吸附、共混、化学反应等方法携带药物，在植入支架后的位置上缓慢释放，增加疗效；(5)具有形状记忆效应，聚乳酸系聚合物获得冷变形成型形状记忆效应的，另外聚己内酯在辐照后获得形状记忆效应已经成为公知技术，(6)便于进行3D打印。
这类材料大多只是含有C、H、O等低电子密度和低比重的元素而不能被X-射线检测，使得医务人员无法了解植入材料在体内的具体形态和位置，无法将其准确放置在病变部位，患者的组织也容易受到伤害，给手术带来了困难，因此，显影型可降解尿道修复支架是目前的研究热点，显影剂主要有钡剂和碘剂，钡剂主要是用于食道和胃肠造影，而碘剂主要用于胆管及胆囊、肾盂及尿路、动脉及静脉等的造影。
临床应用还需要支架主体表面涂覆加载的药物层可治疗或预防尿道良恶性增生狭窄以及避免支架植入后发生尿道增生后再狭窄后加重尿道梗阻。
因此，开发具有更好生物相容性，生物力学性质，显影能力更强、使用更安全的可降解修复尿道支架式是目前的热点。
发明内容
本发明的目的是提供一种显影型可降解修复尿道支架，是一种生物复合材料支架；
一种显影型可降解修复尿道支架，其特征在于：组分包括：50～100重量份可降解医用材料A、0.1～50重量份愈合修复材料B、0.001～0.05重量份显影剂C、0.001～0.05重量份抗高尿酸药物D、0.001～0.05重量份维生素。
一种显影型可降解修复尿道支架，其特征在于：组分包括：50重量份可降解医用材料A、5重量份愈合修复材料B、0.05重量份显影剂C、0.02重量份抗高尿酸药物D、0.001重量份维生素。
一种显影型可降解修复尿道支架，其特征在于：组分包括：100重量份可降解医用材料A、8重量份愈合修复材料B、0.02重量份显影剂C、0.008重量份抗高尿酸药物D、0.002重量份维生素。
一种显影型可降解尿道修复支架，其特征在于：
其制备工艺包括：以可降解医用材料A作为基体材料，通过加入愈合修复材料B和显影剂C、抗高尿酸药物D、维生素后，制备而成；
可降解医用材料A为：聚乳酸(PLA)、聚乙醇酸(PGA)或聚羟基乙酸、聚三亚甲基碳酸酯(PTMC)、聚已内酯(PCL)等和其共聚物，如：聚乳酸-聚羟基乙酸共聚物(PLGA)、聚乳酸-聚三亚甲基碳酸酯共聚物(DL-PLA-PTMC)等中的一种或几种；
愈创修复材料B为：羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖、壳聚糖乳酸盐、壳聚糖季铵盐、壳聚糖盐酸盐、丝素蛋白等中的1种或几种。
显影剂C：选自钡剂、生物显影剂、离子显影剂或非离子显影剂。如钡剂：硫酸钡，离子型显影剂：碘克酸、碘克沙酸、泛影酸、泛影葡胺、碘他拉葡胺、碘酞酸盐，非离子型：碘海醇、碘美普尔、碘异肽醇、碘维索、碘普罗胺、碘帕醇、碘佛醇、碘曲仑、碘克沙醇中的1种或几种；；
抗高尿酸药物D为：黄嘌呤氧化酶抑制剂、尿酸盐阴离子转运蛋白抑制剂、尿酸氧化酶类似物中的一种或多种；
维生素为：维生素B1、维生素B2中的一种或多种。
为实现上述发明目的，本发明采用以下技术方案予以实现：
显影型可降解修复尿道支架的制备工艺可以采用五种制备方式：注塑、灌注、挤出、3D打印、电纺技术。
注塑技术：采用注塑机加工成可降解医用材料A螺纹管，然后将愈合修复材料B涂于管外螺纹凹槽内；
灌注技术：采用灌注机加工成可降解医用材料A螺纹管，然后将愈合修复材料B涂于管外螺纹凹槽内；
3D打印技术：采用3D打印可降解医用材料A螺纹管，然后将愈创修复材料B涂于管外螺纹凹槽内。
电纺技术：分别将可降解医用材料A和愈创修复材料B制胶，利用电纺技术制备螺纹管，螺纹凹槽内挂有愈创修复材料B。
挤出工艺：主要工序如下：挤出→定径→冷却→涂层→干燥→定型、组装→灭菌。由挤出机将可降解医用材料A挤出管状，后续加工成螺纹管，或直接由挤出机挤出螺纹管；然后将愈创修复材料B涂于管外壁螺纹凹槽内；显影：显影剂可采用钡剂、生物显影剂、离子显影剂或非离子显影剂。显影剂可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁，或在定型工序中进行针点显影制备显影点，显影点分布在管壁，纵向分布间距为1mm～50mm，或后续添加显影线。
挤出工艺的说明：
(1)挤出螺纹管：挤出成套设备包括挤出机、牵引装置、定径装置、冷却装置配套设备。挤出温度：50～300℃。挤出材料为生物可降解材料：聚乳酸(PLA)、聚乙醇酸(PGA)或聚羟基乙酸、聚三亚甲基碳酸酯(PTMC)、聚已内酯(PCL)等和其共聚物，如：聚乳酸-聚羟基乙酸共聚物(PLGA)、聚乳酸-聚三亚甲基碳酸酯共聚物(DL-PLA-PTMC)等中的一种或几种，加入的比例范围分别均为：0～100％。螺纹凹槽的螺距为：0～20mm。
(2)冷却：冷却可通过风冷、水浴中的一种或两种方式结合进行冷却。
(3)愈创涂层：通过自动点胶机或其它方式，将胶液点涂到螺纹管的外壁螺旋凹槽内，干燥，愈合修复功能材料是由羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖、壳聚糖乳酸盐、壳聚糖季铵盐、壳聚糖盐酸盐、丝素蛋白等中的1种或几种。
取上述材料制成的胶体溶液，加入显影剂(0.01～5重量份)、抗高尿酸药物D、维生素，使其混合均匀，配制成愈创涂层胶体溶液；
(4)干燥：采用隧道干燥的方式，干燥温度为(0～150℃)，牵引速度为：0～1m/S，隧道长度：0～20m。
(5)显影：显影剂可采用钡剂、生物显影剂、离子显影剂或非离子显影剂。含显影剂的胶体溶液可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁，或在定型工序中将显影剂的酰基化甲壳素胶体溶液进行针点显影制备显影点，显影点分布在管壁，纵向分布间距为1mm～50mm，或后续添加显影线。
(6)灭菌：灭菌方式采用环氧乙烷、辐照灭菌、臭氧灭菌中的一种或几种。
本发明的产品用途：用于制备复合材料组织工程支架，尿道支架。
本发明的产品功能特点：该可降解复合材料能够被人体吸收，具有很好的生物相容性，产品为显影型支架。显影剂可采用钡剂、生物显影剂、离子显影剂或非离子显影剂；可以更快捷地判断植入材料的形态和位置，支架降解时间可控。可根据临床的不同需求制备不同降解时间的产品；支架具有促愈合修复作用。对各类尿道损伤创面具有促进愈合修复、减少瘢痕生成的作用，制备方法简单，成本低，对环境友好，适合工业化生产。
试验例1 可复合材料的筛选：
(1)膜片的制备：
壳聚糖膜片的制备：分别称取壳聚糖粉(脱乙酰度80、85、80、95％)3g，加入重量百分浓度为3％的醋酸溶液97ml，搅拌溶解，配制成重量百分浓度为3％的壳聚糖胶体溶液。称取10g壳聚糖胶体溶液置于边长为50mm×50mm的PP方盘中，于通风厨中静置干燥。将干燥的膜片置于重量百分浓度为60％的乙醇水溶液中浸泡、水洗至中性，铺平于玻璃板上干燥，制得四种规格的壳聚糖膜片。
用直径为5mm的环钻分别将上述壳聚糖膜片制备成直径为5mm的圆片，于重量百分浓度为75％的乙醇水溶液中浸泡消毒，无菌蒸馏水洗涤，无菌条件下干燥、包装，备用，分别制得无菌壳聚糖圆片。
(2)血管内皮细胞在膜片上的贴附生长比较：
实验分为4个组：脱乙酰度80％壳聚糖膜片组、脱乙酰度85％壳聚糖膜片组、脱乙酰度90％壳聚糖膜片组、脱乙酰度95％壳聚糖膜片组、。分别将上述4种无菌圆片浸入D-Hank′s液中浸泡12h，壳聚糖膜片组在无菌条件下分别将4片无菌壳聚糖圆片平铺在96孔细胞培养板的4个孔的底部，得4孔壳聚糖膜片组。将对数生长期的人脐静脉内皮细胞(HUVEC细胞)经胰酶消化、D-Hank′s液清洗、DMEM培养基(10％血清)调整细胞密度至2×104个/mL，得HUVEC细胞细胞悬液。将细胞悬液接种于96孔细胞培养板上的壳聚糖膜片组的培养孔中，每孔加细胞悬液200uL，于37℃下，5％CO2培养箱中静置培养72h，观察各组细胞的贴附生长情况，并拍照。
实验结果显示，HUVEC细胞经过72h的培养，
细胞在脱乙酰度85％壳聚糖膜片上的贴附生长情况最好，80％细胞形态正常，边界清晰，贴壁伸展，细胞数量多；
细胞在脱乙酰度80％壳聚糖膜片上次之，60％细胞贴壁伸展，形态正常，有少数细胞呈球形，未伸展，细胞数量多；
细胞在脱乙酰度90％壳聚糖膜片上的贴附生长情况不佳，约40％细胞贴壁伸展，形态正常，约一半细胞呈球形，不贴壁；
细胞在脱乙酰度95％壳聚糖膜片上的贴附生长情况较差，约60％细胞呈球形不贴壁，膜片上细胞数量少。
因此选择脱乙酰度85％壳聚糖优选为可降解复合材料。
显影型可降解修复尿道支架结构说明：
支架为一外壁带有螺旋凹槽的管状结构。
纵剖面凹槽螺距：0～20mm；形状：倒三角、正三角、半形、圆弧状、正方形、长方形或者不规则图形；凹槽深度不大于壁厚。
显影位置及形式：显影点或显影线。显影点分布在管壁外侧，纵向分布间距为1mm～50mm。显影线1-3条，均匀分布。
支架的内径范围：1mm～30mm，壁厚范围：0.1mm～5mm，长度范围：1cm～50cm。
支架两端同侧可有一卡翼，便于固定支架，防止位移。根据临床不同需求制备不同规格的产品。卡翼内侧可以设置一孔，便于空气的排出。卡翼可以设置导流管，便于导流。
支架降解时间为：2周至3年不等，降解时间可通过挤出材料的比例、材料分子量、支架的结构尺寸进行控制。
具体实施方式
实施例1
挤出螺纹管：挤出成套设备包括挤出机、牵引装置、定径装置、冷却装置配套设备。挤出温度：150℃。挤出材料为生物可降解材料：聚乳酸-聚羟基乙酸共聚物(PLGA)。螺纹凹槽的螺距为：10mm。
冷却：通过风冷冷却。
愈创涂层：通过自动点胶机等设备，将胶液点涂到螺纹管的外壁螺旋凹槽内，干燥，用无水乙醇洗涤，干燥，愈合修复功能材料是由多糖制成的胶体溶液。
愈合修复功能材料制备方法为：称取壳聚糖粉50g，加入玻璃反应容器中，加入酰化试剂丙酸酐溶液130mL，加入乙醇120ml，搅拌均匀，控制反应温度为35℃，加入乙磺酸溶液1.0ml作为催化剂，搅拌反应10h。反应毕，过滤，固液分离，固形物水洗涤至中性，固液分离，95％乙醇脱水，50℃加热干燥，得脱乙酰度为90％酰基化甲壳素粉；
取脱乙酰度为90％的酰基化甲壳素粉14.5g，加入75％的乙酸溶液85.5ml作溶剂，搅拌溶解，配制成重量百分浓度为14.5％的酰基化甲壳素胶体溶液；
干燥：采用隧道干燥的方式，干燥温度为(60℃)，牵引速度为：0.5m/S，隧道长度：5m。
显影：取重量百分浓度为14.5％的酰基化甲壳素胶体溶液100g，加入显影剂碘海醇100mg、吲哚美辛10mg、维生素B1 5mg，使其混合均匀，配制成含显影剂的酰基化甲壳素胶体溶液；
显影剂的酰基化甲壳素胶体溶液可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁；
显影点分布在管壁，纵向分布间距为20mm。
弯管：通过加热塑形的方式，使管的一端具有一定弧度.
灭菌：辐照灭菌。
实施例2
挤出螺纹管：挤出成套设备包括挤出机、牵引装置、定径装置、冷却装置配套设备。挤出温度：150℃。挤出材料为生物可降解材料：聚乳酸-聚羟基乙酸共聚物(PLGA)。螺纹凹槽的螺距为：10mm。
冷却：通过风冷冷却。
愈创涂层：通过自动点胶机等设备，将胶液点涂到螺纹管的外壁螺旋凹槽内，干燥，用无水乙醇洗涤，干燥，愈合修复功能材料是由多糖制成的胶体溶液。
愈合修复功能材料制备方法为：称取壳聚糖粉50g，加入玻璃反应容器中，加入酰化试剂丙酸酐溶液130mL，加入乙醇120ml，搅拌均匀，控制反应温度为35℃，加入乙磺酸溶液1.0ml作为催化剂，搅拌反应10h。反应毕，过滤，固液分离，固形物水洗涤至中性，固液分离，95％乙醇脱水，50℃加热干燥，得脱乙酰度为90％酰基化甲壳素粉；
取脱乙酰度为90％的酰基化甲壳素粉14.5g，加入75％的乙酸溶液85ml作溶剂，加入500mg聚乙二醇6000，搅拌溶解，配制成重量百分浓度为14.5％的酰基化甲壳素胶体溶液；
干燥：采用隧道干燥的方式，干燥温度为(60℃)，牵引速度为：0.5m/S，隧道长度：5m。
显影：取重量百分浓度为14.5％的酰基化甲壳素胶体溶液100g，加入显影剂碘海醇100mg，丙磺舒2mg、维生素B2 5mg，使其混合均匀，配制成含显影剂的酰基化甲壳素胶体溶液；
显影剂的酰基化甲壳素胶体溶液可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁；
显影点分布在管壁，纵向分布间距为20mm。
弯管：通过加热塑形的方式，使管的一端具有一定弧度.
灭菌：辐照灭菌。
实施例3
挤出螺纹管：挤出成套设备包括挤出机、牵引装置、定径装置、冷却装置配套设备。挤出温度：150℃。挤出材料为生物可降解材料：聚乳酸-聚羟基乙酸共聚物(PLGA)。螺纹凹槽的螺距为：10mm。
冷却：通过风冷冷却。
愈创涂层：通过自动点胶机等设备，将胶液点涂到螺纹管的外壁螺旋凹槽内，干燥，用无水乙醇洗涤，干燥，愈合修复功能材料是由多糖制成的胶体溶液。
愈合修复功能材料制备方法为：称取壳聚糖粉50g，加入玻璃反应容器中，加入酰化试剂丙酸酐溶液130mL，加入乙醇120ml，搅拌均匀，控制反应温度为35℃，加入乙磺酸溶液1.0ml作为催化剂，搅拌反应10h。反应毕，过滤，固液分离，固形物水洗涤至中性，固液分离，95％乙醇脱水，50℃加热干燥，得脱乙酰度为90％酰基化甲壳素粉；
取脱乙酰度为90％的酰基化甲壳素粉14.5g，加入75％的乙酸溶液85.5ml作溶剂，搅拌溶解，配制成重量百分浓度为14.5％的酰基化甲壳素胶体溶液；
干燥：采用隧道干燥的方式，干燥温度为(60℃)，牵引速度为：0.5m/S，隧道长度：5m。
显影：取重量百分浓度为14.5％的酰基化甲壳素胶体溶液100g，加入显影剂硫酸钡100mg，别嘌呤醇2mg、维生素B2 5mg，使其混合均匀，配制成含显影剂的酰基化甲壳素胶体溶液；
显影剂的酰基化甲壳素胶体溶液可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁；
显影点分布在管壁，纵向分布间距为20mm。
弯管：通过加热塑形的方式，使管的一端具有一定弧度.
灭菌：辐照灭菌。
实施例4
挤出螺纹管：挤出成套设备包括挤出机、牵引装置、定径装置、冷却装置配套设备。挤出温度：150℃。挤出材料为生物可降解材料：聚乳酸-聚羟基乙酸共聚物(PLGA)。螺纹凹槽的螺距为：10mm。
冷却：通过风冷冷却。
愈创涂层：通过自动点胶机等设备，将胶液点涂到螺纹管的外壁螺旋凹槽内，干燥，用无水乙醇洗涤，干燥，愈合修复功能材料是由多糖制成的胶体溶液。
愈合修复功能材料制备方法为：称取壳聚糖粉50g，加入玻璃反应容器中，加入酰化试剂丙酸酐溶液130mL，加入乙醇120ml，搅拌均匀，控制反应温度为35℃，加入乙磺酸溶液1.0ml作为催化剂，搅拌反应10h。反应毕，过滤，固液分离，固形物水洗涤至中性，固液分离，95％乙醇脱水，50℃加热干燥，得脱乙酰度为90％酰基化甲壳素粉；
取脱乙酰度为90％的酰基化甲壳素粉14.5g，加入75％的乙酸溶液85ml作溶剂，加入500mg聚乙二醇6000，搅拌溶解，配制成重量百分浓度为14.5％的酰基化甲壳素胶体溶液；
干燥：采用隧道干燥的方式，干燥温度为(60℃)，牵引速度为：0.5m/S，隧道长度：5m。
显影：取重量百分浓度为14.5％的酰基化甲壳素胶体溶液100g，加入显影剂硫酸钡50mg，苯溴马隆2mg、维生素B2 5mg，使其混合均匀，配制成含显影剂的酰基化甲壳素胶体溶液；
显影剂的酰基化甲壳素胶体溶液可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁；
显影点分布在管壁，纵向分布间距为20mm。
弯管：通过加热塑形的方式，使管的一端具有一定弧度.
灭菌：辐照灭菌。
实施例5
上述实施例中的显影型可降解尿道支架均具有较好的机械强度，压握回弹性能较好。通过电子万能拉力机进行了力学性能的测试，显影型可降解尿道支架力学性能如表1，表明显影型可降解尿道支架的机械性能较好。
并使用球囊分别对于实施例1-4所制备的支架进行反复扩张10次，然后在扫描电子显微镜(SEM)分别观察和统计其涂层的破裂脱落平均处数：
表1.显影型可降解尿道支架的力学性能测试结果
显影型可降解尿道支架1-4分别来源于实施例1-4。
实施例6
显影型可降解尿道支架的激光切割加工：将飞秒激光器架设在操作控制平台上，与控制计算机、气动电机、切割头等辅助设备连接组成显影型可降解尿道支架加工操作系统。将上述实施例1～实施例4中的显影型可降解尿道支架分别固定于支架加工操作系统上的可旋转夹头上，计算机根据预先设定的切割图案编程，控制支架加工操作系统工作，通过飞秒激光器的聚焦光斑的移动，激光脉冲对支架进行切割加工，
显影型支架管材1，管长4cm，管腔直径2.7mm，管壁厚度330μm；
显影型支架管材2，管长3cm，管腔直径2.6mm，管壁厚度320μm；
显影型支架管材3，管长3cm，管腔直径3.4mm，管壁厚度330μm；
显影型支架管材4，管长2cm，管腔直径3.1mm，管壁厚度310μm；
管壁均具有通透的规则或不规则的孔洞结构或图案结构。
实施例7
分别取实施例1-4的显影型可降解尿道支架，各取2个，单独包装，经环氧乙烷灭菌，作犬股动脉植入用。实验用杂种犬4只，禁食禁水12h，用陆眠宁II按0.05ml/kg剂量肌注麻醉后，将犬仰卧位固定于手术台上，去除腹部处毛发，用碘伏消毒，无菌洞巾覆盖于手术部位，依次切开皮肤和肌肉组织，结扎小血管，静脉注射肝素(1mg/Kg体重)，4只犬各放一个显影型可降解尿道支架，用6-0血管缝线缝合切口，松开近、远心端血管夹后，仔细观察吻合口有无渗血，确定无渗血后逐层缝合肌肉组织和皮肤，皮肤表面涂抹碘伏，并用无菌纱布包扎。术后动物给予青霉素80万U肌注3d，预防感染，正常饲养，观察动物的一般情况，并于实验后3个月和6个月用多普勒超声检查手术部位的尿道流通畅情况。
多普勒超声检查结果显示，4只犬显影型可降解尿道支架植入后3个月，尿道内液体流动正常，显影型可降解尿道支架部位搏动明显。植入后6个月，尿道内通畅良好，未见明显狭窄，通过频谱观察到明显的尿道搏动。
每个月使用X光线显影仪观察其显影效果，实施例1-4显影效果明显，实施例1、4显影效果更持久稳定。
12个月后，支架已经基本完全降解，尿道病变处得到治愈。
Claims (5)
1.一种显影型可降解修复尿道支架，其特征在于：组分包括：50～100重量份可降解医用材料A、0.1～50重量份愈合修复材料B、0.001～0.05重量份显影剂C、0.001～0.05重量份抗高尿酸药物D、0.001～0.05重量份维生素。
2.根据权利要求1的一种显影型可降解修复尿道支架，其特征在于：
其制备工艺包括：以可降解医用材料A作为基体材料，通过加入愈合修复材料B和显影剂C、抗高尿酸药物D、0.01～0.5重量份维生素后，制备而成；
可降解医用材料A为：聚乳酸、聚乙醇酸或聚羟基乙酸、聚三亚甲基碳酸酯、聚己内酯(PCL)、聚乳酸-聚羟基乙酸共聚物、聚乳酸-聚三亚甲基碳酸酯共聚物等中的一种或几种；
愈创修复材料B为：羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖、壳聚糖乳酸盐、壳聚糖季铵盐、壳聚糖盐酸盐、丝素蛋白等中的一种或几种；
显影剂C为：显影剂可采用钡剂、生物显影剂、离子显影剂或非离子显影剂。如钡剂：硫酸钡，离子型显影剂：碘克酸、碘克沙酸、泛影酸、泛影葡胺、碘他拉葡胺、碘酞酸盐，非离子型：碘海醇、碘美普尔、碘异肽醇、碘维索、碘普罗胺、碘帕醇、碘佛醇、碘曲仑、碘克沙醇中的1种或几种；
抗高尿酸药物D为：黄嘌呤氧化酶抑制剂、尿酸盐阴离子转运蛋白抑制剂、尿酸氧化酶类似物中的一种或多种；
维生素为：维生素B1、维生素B2中的一种或多种。
3.根据权利要求2的一种显影型可降解修复尿道支架，其特征在于：
采用五种制备方式：注塑、灌注、挤出、3D打印、电纺技术。
4.根据权利要求3的一种显影型可降解修复尿道支架，其特征在于：
注塑技术：采用注塑机加工成可降解医用材料A螺纹管，然后将愈合修复材料B涂于管外螺纹凹槽内；
灌注技术：采用灌注机加工成可降解医用材料A螺纹管，然后将愈合修复材料B涂于管外螺纹凹槽内；
3D打印技术：采用3D打印可降解医用材料A螺纹管，然后将愈创修复材料B涂于管外螺纹凹槽内；
电纺技术：分别将可降解医用材料A和愈创修复材料B制胶，利用电纺技术制备螺纹管，螺纹凹槽内挂有愈创修复材料B；
挤出工艺：主要工序如下：挤出→定径→冷却→涂层→干燥→定型(切割、弯管)、组装→灭菌。
5.根据权利要求4的一种显影型可降解修复尿道支架，其特征在于：
挤出工艺：由挤出机将可降解医用材料A挤出管状，后续加工成螺纹管，或直接由挤出机挤出螺纹管；然后将愈创修复材料B涂于管外壁螺纹凹槽内；显影：显影剂可采用钡剂、生物显影剂、离子显影剂或非离子显影剂；显影剂可通过在支架管通过挤出机挤出时一起挤出制备，制备成线状，均匀分布在支架管的外壁，或在定型工序中进行针点显影制备显影点，显影点分布在管壁，纵向分布间距为1mm～50mm，或后续添加显影线。
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