WO2010043177A1

WO2010043177A1 - Human body tube substitute of biological induction type

Info

Publication number: WO2010043177A1
Application number: PCT/CN2009/074441
Authority: WO
Inventors: 周星
Original assignee: Zhou Xing
Priority date: 2008-10-15
Filing date: 2009-10-14
Publication date: 2010-04-22

Abstract

A human body tube substitute of biological induction type uses an elastic supporting tube (1) covered with a film (12) and accompanied with connecting pieces (2). An absorbable coating (3) adheres to the outwall of the supporting tube (1), and the absorbable coating (3) includes growth factors (32) and/or seed cells (33).

Description

说明书 Instruction manual

Title of Invention:生物诱导型人体腔管代用品技术领域 Title of Invention: Biologically induced human body tube substitutes

技术领域 Technical field

[1] 本发明涉及一种人体腔管切除后重建使用的代用品，特别是食管切除后进行食管重建吋使用的人工食管，或气管切除后进行气管重建吋的人工气管，或尿道损伤后尿道重建吋的人工尿道。 [1] The present invention relates to a substitute for reconstruction after removal of a human lumen, in particular, an artificial esophagus for esophageal reconstruction after esophagectomy, or an artificial trachea for tracheal reconstruction after tracheal resection, or a urethra after urethral injury Reconstruct the artificial urethra of the sputum.

背景技术 Background technique

[2] 食管癌是中国常见病，在常见的恶性肿瘤发病率中位居第二，发病率为 21/10 万，即年新增病人 27.3万以上，而且目前发病率还有上升的趋势，危害极大。同吋因各种原因导致的食管损伤，特别是车祸造成的食管损伤，也呈上升趋势。如何有效实施食管重建术，是减少死亡率和提高病人生存质量的关键。 [2] Esophageal cancer is a common disease in China, ranking second among the common incidences of malignant tumors. The incidence rate is 21/100,000, that is, more than 273,000 new patients are added each year, and the current incidence rate is still rising. It is extremely harmful. Esophageal injuries caused by various causes, especially esophageal injuries caused by car accidents, are also on the rise. How to effectively implement esophageal reconstruction is the key to reducing mortality and improving the quality of life of patients.

[3] 食管癌的病灶通常具有多中心跳跃性的特点，至今为止，食管癌最有效的治疗方法仍是釆用外科手术切除病变食管，并同吋应用替代物对食管通道进行食管重建，以恢复食管通道。由于食管的供血血管是细小的血管网络，食管移植吋细小的血管很难吻合，移植的食管的血液供应难以重建，因而食管很难像心脏、肝、肾等器官那样进行器官移植。目前，临床上主要釆用患者自身的其它组织或器官来恢复重建食管通道，如将胃或肠从腹腔上提至胸腔或颈部与保留的正常食管断端吻合来恢复重建食管通道，这种传统的手术方法有如下缺点：手术创伤大、吋间长、器官解剖位置移位导致心肺功能受影响和消化功能紊乱等 [3] The lesions of esophageal cancer usually have the characteristics of multi-center hopping. So far, the most effective treatment for esophageal cancer is to use surgical resection of the diseased esophagus and the use of alternatives for esophageal recanal esophageal recanalization. Restore the esophageal passage. Since the blood supply blood vessels of the esophagus are small blood vessel networks, the small blood vessels of the esophagus transplant are difficult to match, and the blood supply of the transplanted esophagus is difficult to reconstruct, so that the esophagus is difficult to perform organ transplantation like the heart, liver, kidney and the like. At present, the clinical use of other tissues or organs of the patient itself to restore the reconstruction of the esophageal passage, such as lifting the stomach or intestine from the abdominal cavity to the chest or neck and maintaining the normal esophageal stump to restore the reconstruction of the esophageal passage. Traditional surgical methods have the following disadvantages: large surgical trauma, long intercondylar space, and dislocation of organs and anatomical position lead to affecting cardiopulmonary function and digestive disorders.

[4] 1913年，美国胸外科医生 Fnmz J.A.Torek成为世界上第一位临床使用人工食管的医生， Torek为一个 67岁的女性食管癌患者使用了体外安置的人工食管。这项临床的结果，得到了一个重要的结论：食管最重要的功能是食物的通道功能，只要食物能经过通道进入胃，患者就能长期生存。 [4] In 1913, American thoracic surgeon Fnmz J.A. Torek became the world's first doctor to use artificial esophagus clinically. Torek used an artificially placed artificial esophagus for a 67-year-old female esophageal cancer patient. The clinical outcome has led to an important conclusion: The most important function of the esophagus is the passage function of the food. As long as the food can enter the stomach through the passage, the patient can survive for a long time.

[5] 由于体外人工食管患者难以接受，人们就一直想开发体内植入的人工食管。近年来，中国形成了生物降解型人工食管、生物型人工食管和记忆合金人工食管的三足鼎立的科研开发局面。 [5] Because in vitro artificial esophageal patients are difficult to accept, people have been trying to develop artificial esophagus implanted in the body. Near Over the years, China has formed a three-legged research and development situation of biodegradable artificial esophagus, bioartificial esophagus and memory alloy artificial esophagus.

[6] 孙康等申请了 "可降解复合人工食管及其制备方法"的专利，申请号 2003101079 [6] Sun Kang et al. applied for the patent of "degradable composite artificial esophagus and its preparation method", application number 2003101079

65.2, 构建了聚氨酯 -胶原蛋白壳聚糖复合人工食管，从其公开发表的论文的数据看，吻合口瘘、新生食管狭窄等技术问题还有待解决。此外，上海第二军医大学附属长海医院胸心外科的鲍春荣等也在进行人工生物可降解支架聚乳酸- 聚乙醇酸种植人食管上皮细胞的实验研究。暨南大学的徐国风教授在实用新型专利 03222722.1中公开了用生物降解材料制造的"一种具有力学顺应性的人工食管"，但未能检索到动物实验的数据。 65.2. A polyurethane-collagen chitosan composite artificial esophagus was constructed. From the data of the published paper, technical problems such as anastomotic leakage and neonatal esophageal stricture have yet to be resolved. In addition, Bao Chunrong, from the Department of Thoracic and Cardiovascular Surgery, Changhai Hospital, Shanghai Second Military Medical University, also conducted experimental research on artificial biodegradable stent polylactic acid-polyglycolic acid implanted esophageal epithelial cells. Professor Xu Guofeng of Jinan University disclosed "a kind of artificial esophagus with mechanical compliance" made of biodegradable materials in utility model patent 03222722.1, but failed to retrieve data from animal experiments.

[7] 张兰军、戎铁华在 2003年申请了"人工食管"的专利，申请号： 03113536.6, 公开了一种生物型人工食管，是用猪的主动脉、软骨、腹膜等组织进行去抗原化处理 (灭活)后缝制而成，从公开发表的论文的数据看，釆用不同生物材料人工食管以不同吻合方式，吻合口瘘的发生率可由 40%(6/15)降到 6.67%(2/30)，但新生食管的狭窄问题有待解决。 [7] Zhang Lanjun and Yan Tiehua applied for the patent of "artificial esophagus" in 2003, application number: 03113536.6, which discloses a bioartificial artificial esophagus, which is de-antigenicized by tissues such as aorta, cartilage and peritoneum of pigs. Inactivated), after sewing, according to the data of published papers, the incidence of anastomotic leakage can be reduced from 40% (6/15) to 6.67% by using different artificial materials of artificial esophagus. /30), but the problem of stenosis of the newborn esophagus remains to be resolved.

[8] 1992年，基于镍钛形状记忆合金技术的自膨式食道裸支架开始在临床上使用，用于晚期食管癌患者食管狭窄的扩张治疗，取得明显的疗效，并在 1994年开始在临床上普及。随着记忆合金食道裸支架的广泛使用，其缺点也逐步明显，癌组织能穿过裸支架的网孔，向心生长，导致再狭窄。于是 1995年开始推出了记忆合金带膜食道支架，迄今，记忆合金带膜食道支架已在临床上成功应用了 13 年，安置了食道支架的晚期食管癌患者，直到因癌细胞扩散死亡前，仍然可以正常进食。带膜食道支架不仅用于晚期食管癌患者食管狭窄的扩张治疗，而且用于食管瘘的治疗。大范围的食管瘘相当于局部的食管缺损，釆用记忆合金带膜食道支架治疗有良好的疗效。 [8] In 1992, self-expanding esophageal bare stents based on nickel-titanium shape memory alloy technology began to be used clinically for the expansion treatment of esophageal stenosis in patients with advanced esophageal cancer, and achieved significant results, and began clinically in 1994. Popularized. With the widespread use of the memory alloy esophageal bare stent, its shortcomings are gradually becoming apparent. The cancer tissue can pass through the mesh of the bare stent and grow centripetally, leading to restenosis. So in 1995, the memory alloy-coated esophageal stent was introduced. So far, the memory alloy-coated esophageal stent has been successfully applied clinically for 13 years, and patients with advanced esophageal cancer with esophageal stents are placed until they die due to cancer cell proliferation. Can eat normally. Membrane esophageal stents are not only used for dilatation of esophageal stenosis in patients with advanced esophageal cancer, but also for the treatment of esophageal fistula. A wide range of esophageal fistulas are equivalent to local esophageal defects, and the use of memory alloy with esophageal stents has a good effect.

[9] 本发明人于 1999年 6月开始研制人工食管，在初步的动物试验的基础上，于 200 [9] The inventor began to develop artificial esophagus in June 1999, based on preliminary animal experiments, at 200

1年 1月提交的中国专利申请 01107515.5中（专利名称：新型人造腔管代用品），公开了一种带连接环的人造腔管代用品，釆用了带膜记忆合金丝网管体上安装减张连接环的设计，用于食道重建或气管重建。随后在本人申请的中国专利 200 610122449.0中进行了完善。目前，已经进行了 9年的动物实验，最长的动物实验猪的存活期已超过 5年，目前相关的产品已经获得中国政府的临床试验许可，正处于临床试验阶段。 In the Chinese patent application 01107515.5 (patent name: new artificial cavity tube substitute) submitted in January 1st, a man-made cavity tube substitute with a connecting ring was disclosed, which was installed on the tube with a membrane memory alloy. The connection ring is designed for esophageal reconstruction or tracheal reconstruction. It was subsequently improved in the Chinese patent 200 610122449.0 that I applied for. Currently, 9 years of animal experiments have been carried out, the longest animal experiment. The pig has survived for more than 5 years, and the relevant products have been approved by the Chinese government for clinical trials and are in clinical trials.

[10] 经过近百年的不懈努力，特别是近 50年来生物医用材料和生物技术的飞速进步，人工食管的研究开发已经到了核心技术突破的前夜。通过对一百年来的技术基础的总结，可以得到以下的结论：（1) 食管最重要的功能是食物的通道功能，只要食物能经过通道进入胃，患者就能长期生存；（2) 在用杂种犬、杂种猪进行的动物实验中，在植入的人工食管外发现了一条包裹人工食管的通道，即所谓"新生食管"； (3) 新生食管能上皮化； (4) 新生食管会狭窄。 [10] After nearly 100 years of unremitting efforts, especially the rapid progress of biomedical materials and biotechnology in the past 50 years, the research and development of artificial esophagus has reached the eve of the breakthrough of core technology. By summarizing the technical basis of the past 100 years, the following conclusions can be drawn: (1) The most important function of the esophagus is the channel function of the food. As long as the food can enter the stomach through the channel, the patient can survive for a long time; (2) In animal experiments with hybrid dogs and hybrid pigs, a passage for artificial esophagus was found outside the implanted artificial esophagus, the so-called "new esophagus"; (3) neonatal esophagus can be epithelialized; (4) new esophagus narrow.

[11] 但在新生食管的形成原因和新生食管的组织学结构上各有较大分歧。本发明人在 9年的动物试验的研究中，通过对 30天至 4年的动物试验的标本进行了大量的组织学分析后认为新生食管是食管黏膜覆盖的疤痕性管道。因而，本发明人认为植入的人工食管要获得成功，最核心的有二条。第一，人工食管的两个吻合端不能出现吻合口瘘，人工食管植入后吻合口瘘发生率为 0%是首要目标，这点在人工食管植入后的早期尤其重要，不能避免吻合口瘘就有可能面临手术失败。第二，人工食管在体内滞留的吋间至少要长于 6个月才能有效缓解新生食管的疤痕组织的收缩力，防止新生食管的狭窄。比较理想的支撑吋间为 18个月至 30 个月。在 18个月至 30个月后新生食管不仅能上皮化而且疤痕组织能稳定，这吋即便拆除人工食管的支撑和保护，新生食管仍然不会狭窄和感染。因此，连接环对于人工食管的管体而言，非常重要。连接环能有效的减少食管蠕动对植入管体的影响，从而防止吻合口瘘和早期脱管，直接决定了手术的成败。 [11] However, there are major differences in the causes of neonatal esophagus and the histological structure of the neonatal esophagus. In the nine-year animal test study, the inventors conducted a large amount of histological analysis on a specimen of an animal test of 30 days to 4 years, and considered that the new esophagus is a scar-shaped duct covered by the esophageal mucosa. Therefore, the inventors believe that the artificial esophagus to be implanted is successful, and the core is two. First, there is no anastomotic leakage at the two anastomotic ends of the artificial esophagus. The incidence of anastomotic leakage after artificial esophageal implantation is 0%. This is especially important in the early stage after artificial esophageal implantation, and the anastomosis cannot be avoided. You may face surgery failure. Second, the artificial esophagus stays in the body for at least 6 months to effectively relieve the contractile force of the scar tissue of the newborn esophagus and prevent the narrowing of the new esophagus. The ideal support time is 18 months to 30 months. After 18 months to 30 months, the neonatal esophagus can not only be epithelialized but also the scar tissue can be stabilized. Even if the artificial esophagus is removed and protected, the new esophagus will not be narrowed and infected. Therefore, the connecting ring is very important for the body of the artificial esophagus. The connecting ring can effectively reduce the influence of esophageal peristalsis on the implanted body, thereby preventing the anastomotic leakage and early decoupling, which directly determines the success or failure of the operation.

[12] 综上所述：现有技术中还缺乏一种植入后不发生吻合口瘘，能诱导和促进新生食管的黏膜的生长覆盖，能有效抵抗新生食管疤痕组织的收缩力，防止新生食管的狭窄，并在新生食管的黏膜完全覆盖、且新生食管疤痕组织稳定后，能通过无创伤或微创伤的方式取出或拆除的人工食管。因此，需要对现有的人工食管进行改进。 [12] In summary: In the prior art, there is still a lack of anastomotic leakage after implantation, which can induce and promote the growth coverage of the mucosa of the new esophagus, effectively resist the contractile force of the neonatal esophageal scar tissue, and prevent the neonatal esophagus. The stenosis, and the artificial esophagus that can be removed or removed through a non-invasive or micro-invasive manner after the mucosa of the neonatal esophagus is completely covered and the neonatal esophageal scar tissue is stabilized. Therefore, there is a need to improve existing artificial esophagus.

[13] 此外，在气管切除后，同样面临气管重建的难题；在尿道损伤后，同样面临着尿道重建的难题；在外耳道、鼻腔的损伤修复中，同样面临着外耳道重建、鼻腔重建的难题。这些腔管的重建，都存在新生腔管的狭窄问题和黏膜上皮化的共性问题，都需要在一定吋间内提供有效的支撑，抵抗人体新生腔管的疤痕性狭窄，同吋要利用支撑体的支撑来诱导出新生腔管，并为新生腔管的生长，黏膜上皮化和疤痕组织稳定提供足够的支撑吋间，并在新生腔管黏膜上皮化和疤痕组织稳定后能方便地通过无创伤或微创伤的方式取出或拆除，而现有技术中尚无这种器械，需要提供新的器械。 [13] In addition, after tracheal resection, it also faces the problem of tracheal reconstruction; after urethral injury, it also faces the problem of urethral reconstruction; in the repair of external auditory canal and nasal cavity, it also faces the problem of reconstruction of the external auditory canal and nasal reconstruction. The reconstruction of these lumens has the problem of stenosis of the neonatal lumen and mucosal epithelialization. Common problems need to provide effective support in a certain period of time, to resist the scarring of the human neovascular tube, and to use the support of the support to induce the new lumen, and for the growth of the new lumen, mucosal epithelium Stabilization and scar tissue provide adequate support for the sac and can be easily removed or removed in a non-invasive or minimally invasive manner after neovascularization of the mucosa and stabilization of the scar tissue, which is not available in the prior art. Instruments, new instruments are needed.

对发明的公开 Disclosure of invention

技术问题 technical problem

[14] 本发明的目的在于提供一种生物诱导型人体腔管代用品，用于人体腔管切除后进行重建吋的代用品，能诱导出新生腔管，且为新生腔管的生长，黏膜上皮化和疤痕组织稳定提供足够的支撑吋间，并在新生腔管黏膜上皮化和疤痕组织稳定后能方便地通过无创伤或微创伤的方式取出或拆除。特别是用于：食管切除后进行食管重建吋使用的人工食管，或气管切除后进行气管重建吋的人工气管，或尿道损伤后尿道重建吋的人工尿道。此外还可以用于鼻腔重建和外耳道重建。 [14] The object of the present invention is to provide a bio-inducible human body tube substitute for reconstitution of a human body after resection of the lumen, which can induce a new lumen, and is a growth of the new lumen, mucosa Epithelialization and scar tissue stabilization provide adequate support for the sac and can be easily removed or removed by atraumatic or minimally invasive methods after neovascularization of the mucosal membrane and stabilization of the scar tissue. In particular, it is used for: artificial esophagus for esophageal reconstruction after esophagectomy, or artificial trachea for tracheal reconstruction after tracheal resection, or artificial urethra after reconstruction of the urethra after urethral injury. It can also be used for nasal reconstruction and reconstruction of the external auditory canal.

技术解决方案 Technical solution

[15] 本发明所述的生物诱导型人体腔管代用品，是能在人体中长期植入的薄壁管状物，其包括： A.支撑管，所述支撑管是有弹性的薄壁管状物，其包含：支撑架，设置为弹性的薄壁网状支架；柔性材料膜，设置为使所述柔性材料膜全部或部分包覆支撑架，或者附着在支撑架的内壁上或外壁上； B.连接件，所述连接件固定于支撑管上，设置为通过连接件使支撑管固定于人体食管断端； C . 可吸收涂层，所述可吸收涂层釆用在人体中可降解吸收且能促进组织再生的材料制造，设置在支撑管的外壁上。 [15] The bio-inducible human body tube substitute of the present invention is a thin-walled tube that can be implanted in a human body for a long time, and includes: A. a support tube, the support tube is a flexible thin-walled tube And comprising: a support frame, a thin-walled mesh support provided as an elastic; a flexible material film disposed such that the flexible material film is wholly or partially covered by the support frame, or attached to the inner wall or the outer wall of the support frame; B. a connecting member, the connecting member is fixed on the supporting tube, and is arranged to fix the supporting tube to the broken end of the human esophagus through the connecting member; C. absorbable coating, the absorbable coating is degradable in the human body The material that absorbs and promotes tissue regeneration is fabricated on the outer wall of the support tube.

[16] 优选地，所述可吸收涂层至少包括以下方式：仅含有可在人体中使用的生物降解材料；含有可在人体中使用的生物降解材料和生长因子；含有可在人体中使用的生物降解材料和种子细胞；以及含有可在人体中使用的生物降解材料、生长因子和种子细胞。 [16] Preferably, the absorbable coating comprises at least the following means: containing only biodegradable materials that can be used in humans; containing biodegradable materials and growth factors that can be used in humans; and containing those that can be used in humans. Biodegradable materials and seed cells; and biodegradable materials, growth factors, and seed cells that can be used in humans.

[17] 优选地，所述支撑架被柔性材料膜可运动地包覆在柔性材料膜之间。 [17] Preferably, the support frame is movably coated between the flexible material films by a film of flexible material.

[18] 特别地，所述可运动地包覆是指用两层或以上的柔性材料膜来包覆支撑架吋，柔性材料膜之间的结合处在支撑架的网孔中间，或者结合在支撑架的不容易变形部分，而支撑架可在柔性材料膜之间形成的空间内运动，柔性材料膜不对支撑架的运动造成过分的约束。 [18] In particular, the movably coating refers to coating the support frame with two or more layers of flexible material. The joint between the flexible material films is in the middle of the mesh of the support frame, or is combined with the non-deformable portion of the support frame, and the support frame can move in the space formed between the flexible material films, and the flexible material film is not opposite to the support frame. Movement causes excessive restraint.

[19] 优选地，所述柔性材料膜用可吸收手术缝合线缝合固定在支撑架的内壁上或外壁上；或者柔性材料膜用不可吸手术缝合线可拆卸地缝合固定在支撑架的内壁上或外壁上。釆用可吸收手术缝合线吋，可吸收手术缝合线的降解吋间一般大于 6个月，在新生腔管的疤痕组织生长稳定后才降解。 [19] Preferably, the flexible material film is fixed on the inner wall or the outer wall of the support frame by an absorbable surgical suture; or the flexible material film is detachably stitched and fixed on the inner wall of the support frame by a non-absorbable surgical suture. Or on the outer wall. With the absorbable surgical suture, the degradable dilatation of the absorbable surgical suture is generally greater than 6 months, and the scar tissue is not degraded until the growth of the scar tissue of the new lumen is stable.

[20] 优选地，所述支撑架是医用弹性材料丝或纤维编织成的网状结构薄壁管体；或者是医用弹性材料丝绕成的螺旋弹簧组成的网状结构薄壁管体；或者是经过数控加工后形成的能弯曲的有弹性的医用弹性材料网状结构薄壁管体；或者是经过激光雕刻后的能弯曲的有弹性的医用弹性材料网状结构薄壁管体，所述医用弹性材料，至少选自：镍钛形状记忆合金（Nitinol合金）、 β钛合金、医用不锈钢、医用锆合金，医用锆铌合金、医用钛锆铌合金、无镍钛基形状记忆合金、弹性高分子材料。 [20] Preferably, the support frame is a thin-walled tubular body of a mesh material woven by a medical elastic material or a fiber; or a thin-walled tubular body composed of a coil spring wound with a medical elastic material; or Is a bendable elastic medical elastic material mesh structure thin-walled tube body formed by numerical control processing; or a laser-engravable elastic elastic medical elastic material mesh structure thin-walled tube body, Medical elastic material, at least selected from: nickel-titanium shape memory alloy (Nitinol alloy), β titanium alloy, medical stainless steel, medical zirconium alloy, medical zirconium-niobium alloy, medical titanium zirconium-niobium alloy, nickel-free titanium-based shape memory alloy, high elasticity Molecular material.

[21] 优选地，所述生物降解材料至少选自：聚乳酸、聚羟基乙酸、聚羟基丁酯、聚酸酐、聚己内酯、聚偶磷氮、聚磷腈、聚氨基酸、假聚氨基酸、聚原酸酯、聚酯尿垸、聚三亚甲基碳酸酯、聚乙二醇、聚对二氧六环酮、壳聚糖、胶原、明胶、透明质酸、甲壳素、海藻酸盐、藻酸钙凝胶、脱细胞基质、生物玻璃，及其共聚物或混合物。 [21] Preferably, the biodegradable material is at least selected from the group consisting of: polylactic acid, polyglycolic acid, polyhydroxybutyl ester, polyanhydride, polycaprolactone, polyphosphazene, polyphosphazene, polyamino acid, pseudo polyamino acid , polyorthoesters, polyester urethane, polytrimethylene carbonate, polyethylene glycol, polydioxanone, chitosan, collagen, gelatin, hyaluronic acid, chitin, alginate, Calcium alginate gel, acellular matrix, bioglass, and copolymers or mixtures thereof.

[22] 优选地，所述生长因子至少选自：血小板类生长因子（血小板来源生长因子， PDGF; 骨肉瘤来源生长因子 ODGF) 、表皮生长因子类（表皮生长因子， EGF 、转化生长因子， TGF-α和 TGF-β) 、成纤维细胞生长因子（FGF、 a-FGF、 β-F GF) 、类胰岛素生长因子（IGF-I、 IGF-Π) 、神经生长因子（NGF) 、白细胞介素类生长因子（IL-1、 IL-2、 IL-3等）、红细胞生长素（EPO) 、集落刺激因子 (CSF) ' 及其混合物。 [22] Preferably, the growth factor is at least selected from the group consisting of: platelet growth factor (platelet derived growth factor, PDGF; osteosarcoma derived growth factor ODGF), epidermal growth factor (epidermal growth factor, EGF, transforming growth factor, TGF) -α and TGF-β), fibroblast growth factor (FGF, a-FGF, β-F GF), insulin-like growth factor (IGF-I, IGF-Π), nerve growth factor (NGF), interleukin Growth factors (IL-1, IL-2, IL-3, etc.), erythrocyte growth factor (EPO), colony stimulating factor (CSF), and mixtures thereof.

[23] 优选地，所述种子细胞至少选自：自体食管黏膜上皮细胞、自体骨髓间干细胞、同种异体骨髓间干细胞、胚胎干细胞，及其混合物。要按照具体的临床用途来选择具体的种子细胞。 [24] 优选地，所述连接件是用医用柔性材料丝或纤维，通过编织或针织制造的环状结构，连接件釆用的医用柔性材料，至少选自：涤纶（聚对苯二甲酸乙二酯纤维）、聚乙烯、聚丙烯、聚氨酯、聚四氟乙烯。通过连接件与人体腔管的保留端的吻合，能有效减少人体腔管的保留端（如食管保留端、气管保留端）的蠕动对植入的管体的影响，减少和防止蠕动对吻合处的撕裂、切割，从而建立可靠的连接，避免吻合口瘘和早期脱管的发生。 [23] Preferably, the seed cells are at least selected from the group consisting of: autologous esophageal mucosal epithelial cells, autologous bone marrow mesenchymal stem cells, allogeneic bone marrow mesenchymal stem cells, embryonic stem cells, and mixtures thereof. Specific seed cells should be selected for specific clinical use. [24] Preferably, the connecting member is a ring-shaped structure made of woven or knitted with a medical flexible material wire or fiber, and the medical flexible material for the connecting member is at least selected from the group consisting of: polyester (polyethylene terephthalate) Diester fiber), polyethylene, polypropylene, polyurethane, polytetrafluoroethylene. By the matching of the connecting piece with the reserved end of the human lumen tube, the influence of the peristalsis of the reserved end of the human lumen (such as the esophageal retaining end and the tracheal retaining end) on the implanted tubular body can be effectively reduced, and the peristalsis can be reduced and prevented. Tear, cut, and establish a reliable connection to avoid anastomotic leakage and early tube removal.

[25] 优选地，所述柔性材料膜是能在人体中长期植入的医用柔性材料制造的薄膜，至少选自：医用硅胶、聚氨酯、聚四氟乙烯，各种纤维增强性医用柔性薄膜。 [25] Preferably, the flexible material film is a film made of a medical flexible material that can be implanted in a human body for a long time, and is at least selected from the group consisting of: medical silica gel, polyurethane, polytetrafluoroethylene, various fiber-reinforced medical flexible films.

[26] 优选地，所述连接件有两个，连接件的宽度约 3mm〜15mm，分别缝合固定于支撑管的两个端部，距离端部约 5mm〜20mm。 [26] Preferably, there are two connecting members, and the connecting members have a width of about 3 mm to 15 mm, and are respectively sutured and fixed to the two end portions of the supporting tube, and the distance from the end portion is about 5 mm to 20 mm.

[27] 优选地，所述支撑管上设有柔性材料膜，在支撑管端部的柔性材料膜和支撑管中间部的柔性材料膜是釆用不同的柔性材料制造的。 [27] Preferably, the support tube is provided with a film of flexible material, and the flexible material film at the end of the support tube and the flexible material film at the intermediate portion of the support tube are made of different flexible materials.

[28] 优选地，所述支撑管上的近端设置有能将支撑管取出体外的回收线。 [28] Preferably, the proximal end of the support tube is provided with a recovery line capable of taking the support tube out of the body.

[29] 优选地，所述支撑管上的设置有具有单向阀作用的防返流装置。优选地，所述防返流装置是袖套型单向阀式结构或花瓣型结构。其中花瓣型结构分成：二瓣式结构、三瓣式结构、四瓣式结构、五瓣式结构、六瓣式结构。 [29] Preferably, the support tube is provided with an anti-backflow device having a check valve function. Preferably, the anti-backflow device is a sleeve type one-way valve type structure or a petal type structure. The petal structure is divided into two-petal structure, three-petal structure, four-petal structure, five-petal structure and six-petal structure.

[30] 优选地，所述可吸收涂层的厚度在 0. m〜5mm之间，较佳值在 10μηι〜1ηιηι之间。 [30] Preferably, the thickness of the absorbable coating layer is between 0. m and 5 mm, preferably between 10 μηι and 1ηιηι.

有益效果 Beneficial effect

[31] 由于本发明釆用了带连接件的带膜弹性支撑管，其支撑管的外壁上附着有可吸收涂层，可吸收涂层含有在人体中可降解吸收且能促进组织再生的材料，能诱导或促进新生腔管的生长。使用连接件的吻合方式能有效地减少人体保留的腔管断端（如食管、气管）蠕动对植入的带膜弹性支撑管的影响，加上带膜弹性支撑管良好的柔顺性和较强的支撑力，为新生腔管的生长，黏膜上皮化和疤痕组织稳定提供足够的支撑吋间，并在新生腔管黏膜上皮化和疤痕组织稳定后能方便地通过无创伤或微创伤的方式取出或拆除。 [31] Since the present invention employs a membrane-reinforced elastic support tube with a connecting member, an absorbent coating is attached to the outer wall of the support tube, and the absorbable coating contains a material which is degradable and absorbable in the human body and can promote tissue regeneration. , can induce or promote the growth of new lumens. The use of the connector's anastomosis can effectively reduce the impact of the patient's retained lumen end (such as esophagus, trachea) peristalsis on the implanted elastic support tube, plus the membrane elastic support tube is good and strong. The support force provides sufficient support for the growth of the neonatal lumen, mucosal epithelialization and scar tissue stabilization, and can easily pass through the atraumatic or minimally invasive manner after the neoplasia mucosal epithelialization and scar tissue stabilization Remove or remove.

[32] 本发明之生物诱导型人体腔管代用品用于食管切除后进行食管重建吋，可以用做人工食管。使带膜弹性支撑管与保留的食管断端吻合，并用手术线将连接件缝合固定在保留的食管断端上，涂覆在带膜弹性支撑管外的可吸收涂层能促进食管再生。特别是在可吸收涂层中加入能诱导或促进新生食管的生长生物降解材料，或生物降解材料和生长因子；或是生物降解材料和种子细胞；或生物降解材料、生长因子和种子细胞；能加快新生食管的生长，黏膜上皮化，并促进新生食管疤痕组织稳定。在新生食管的黏膜完全覆盖、且新生食管疤痕组织稳定后（约 6个月至 30个月），在消化内镜的直视下，拆除缝合线。能方便将植入的带连接件的覆膜弹性支撑管取出或拆除。如果釆用降解吋间超过 180天的特殊手术线缝合食管断端和连接件（或称呼为连接环，或减张连接环）吋，则无须拆除缝合线，在手术缝合线降解后，支撑管能自动滑脱，掉入胃中，在消化内镜的直视下取出。 [32] The bioinducible human body tube substitute of the present invention is used for esophageal reconstruction after esophagectomy, and can be used as an artificial esophagus. The membrane elastic support tube is matched with the retained esophagus broken end, and the connecting piece is connected by a surgical line The suture is fixed on the retained esophageal end, and the absorbable coating applied outside the membrane elastic support tube promotes esophageal regeneration. In particular, a biodegradable material capable of inducing or promoting neonatal esophagus, or a biodegradable material and a growth factor; or a biodegradable material and a seed cell; or a biodegradable material, a growth factor, and a seed cell; Accelerate the growth of new esophagus, mucosal epithelialization, and promote the stability of neonatal esophageal scar tissue. After the mucosa of the newborn esophagus is completely covered and the neonatal esophageal scar tissue is stabilized (about 6 months to 30 months), the suture is removed under direct vision of the digestive endoscope. It is convenient to take out or remove the implanted elastic support tube with the connector. If the esophageal stump and the connector (or the connecting ring, or the reduced connecting ring) are sutured with a special surgical line that degrades the daytime for more than 180 days, there is no need to remove the suture, after the surgical suture is degraded, the support tube Can automatically slip off, fall into the stomach, and take it out under the direct view of the digestive endoscope.

[33] 本发明之生物诱导型人体腔管代用品用于气管重建吋，可以作为人工气管。将带膜弹性支撑管与保留的气管断端吻合，并用手术线将连接件缝合固定在保留的气管断端上，涂覆在带膜弹性支撑管外的可吸收涂层能促进气管再生。带膜弹性支撑管良好的柔顺性和较强的支撑力，为新生气管的生长，黏膜上皮化和疤痕组织稳定提供足够的支撑吋间，并在新生气管黏膜上皮化和疤痕组织稳定后能方便地通过无创伤或微创伤的方式取出或拆除。 [33] The bioinducible human body tube substitute of the present invention is used for tracheal reconstruction and can be used as an artificial trachea. The membrane elastic support tube is anastomosed to the remaining end of the trachea, and the connector is sutured and fixed on the remaining trachea end by a surgical line, and the absorbable coating coated on the membrane elastic support tube can promote tracheal regeneration. The membrane elastic support tube has good flexibility and strong support force, which provides sufficient support for the growth of the new irritated tube, mucosal epithelialization and scar tissue stability, and is convenient after the neoplastic tube mucosa epithelialization and scar tissue stabilization. The ground is removed or removed by a non-invasive or micro-invasive manner.

[34] 本发明之生物诱导型人体腔管代用品用于尿道重建吋，可以作为人工尿道。将带膜弹性支撑管与保留的尿道断端吻合，并用手术线将连接件缝合固定在保留的尿道断端上，涂覆在带膜弹性支撑管外的可吸收涂层能促进尿道生物诱导型人体腔管代用品再生。带膜弹性支撑管良好的柔顺性和较强的支撑力，为新生尿道的生长，黏膜上皮化和疤痕组织稳定提供足够的支撑吋间，并在新生气管黏膜上皮化和疤痕组织稳定后能方便地通过无创伤或微创伤的方式取出或拆除 [34] The biologically induced human lumen tube substitute of the present invention is used for urethral reconstruction and can be used as an artificial urethra. The membrane elastic support tube is anastomosed to the retained urethral stump, and the connector is sutured and fixed on the retained urethral stump with a surgical line. The absorbable coating coated on the membrane elastic support tube can promote the urethral biological induction type. Human body tube substitutes are regenerated. The membrane elastic support tube has good flexibility and strong support force, which provides sufficient support for the growth of the new urethra, mucosal epithelialization and scar tissue stability, and is convenient after the epithelialization of the new irritated mucosa and the stabilization of the scar tissue. Remove or remove through a non-invasive or micro-invasive manner

[35] 此外，在外耳道、鼻腔的损伤修复中，同样可以使用本发明之生物诱导型人体腔管代用品。 [35] Further, in the repair of damage to the external auditory canal and nasal cavity, the bioinducible human body tube substitute of the present invention can also be used.

附图说明 DRAWINGS

[36] 图 1是本发明之生物诱导型人体腔管代用品的支撑管上的一种单丝编织的可拆卸的支撑架的结构示意图。 [37] 图 2是本发明之生物诱导型人体腔管代用品的结构示意图。 BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a schematic view showing the structure of a monofilament woven detachable support frame on a support tube of a biologically induced human body tube substitute of the present invention. 2 is a schematic view showing the structure of a biologically induced human body tube substitute of the present invention.

[38] 图 3是图 2的 D_D的剖视图的放大图。 3 is an enlarged view of a cross-sectional view of D_D of FIG. 2.

[39] 图 4是釆用柔性材料膜贴附在支撑架外壁的结构吋图 2的 W处局部放大的结构示意图。 Fig. 4 is a partially enlarged structural view of the structure of the outer wall of the support frame attached to the outer wall of the support frame by the flexible material film.

[40] 图 5是釆用柔性材料膜贴附在支撑架内壁的结构吋图 2的 W处局部放大的结构示意图。 [40] Fig. 5 is a partially enlarged structural view of a structure in which the flexible material film is attached to the inner wall of the support frame, and Fig. 2 is W.

[41] 图 6是釆用缝合法 2层柔性材料膜包覆支撑架结构吋图 2的 W处局部放大的结构示意图。 [41] Fig. 6 is a partially enlarged schematic view of the structure of the support frame structure of Fig. 2, which is covered by a two-layer flexible material film.

[42] 图 7是釆用热合法 2层柔性材料膜包覆支撑架结构吋图 2的 W处局部放大吋的结构示意图。 [42] Fig. 7 is a schematic view showing the structure of a partially enlarged crucible at W at Fig. 2, which is covered with a thermal two-layer flexible material film.

[43] 图 8是用 2种不同柔性材料制造柔性材料膜来包覆支撑架吋图 2的 W处局部放大吋的结构示意图。 [43] Figure 8 is a schematic view showing the structure of a partially enlarged W of the support frame of Fig. 2 by fabricating a flexible material film from two different flexible materials.

[44] 图 9是用柔性材料直接来包覆支撑架吋图 2的 W处局部放大吋的结构示意图。 [44] Figure 9 is a schematic view showing the structure of a partially enlarged W at the W of Figure 2, which is directly covered with a flexible material.

[45] 图 10是本发明之交叉网格型生物诱导型人体腔管代用品的结构示意图。 Figure 10 is a schematic view showing the structure of a cross-grid type biologically induced human body tube substitute of the present invention.

[46] 图 11是图 10的 A_A的剖视图的放大图。 Figure 11 is an enlarged view of a cross-sectional view of A_A of Figure 10 .

[47] 图 12是本发明之交叉网格型生物诱导型人体腔管代用品的结构示意图。 Figure 12 is a schematic view showing the structure of a cross-grid type biologically induced human body tube substitute of the present invention.

[48] 图 13是图 12的 C_C的剖视图的放大图。 Figure 13 is an enlarged view of a cross-sectional view taken along line C_C of Figure 12 .

[49] 图 14是本发明之螺旋弹簧型生物诱导型人体腔管代用品的结构示意图。 Figure 14 is a schematic view showing the structure of a coil spring type biologically induced human body tube substitute of the present invention.

[50] 图 15是图 14的 E_E的剖视图的放大图。 Fig. 15 is an enlarged view of a cross-sectional view taken along line E_E of Fig. 14.

[51] 图 16是本发明之激光雕刻型生物诱导型人体腔管代用品的结构示意图。 Figure 16 is a schematic view showing the structure of a laser-engraving bioinductive human body tube substitute of the present invention.

[52] 图 17是图 16的 F_F的剖视图的放大图。 Figure 17 is an enlarged view of a cross-sectional view of F_F of Figure 16 .

[53] 图 18是本发明之全覆膜生物诱导型人体腔管代用品的结构示意图。 Figure 18 is a schematic view showing the structure of a full-coated bioinducible human body tube substitute of the present invention.

[54] 图 19是图 18的 G_G的剖视图的放大图。 19 is an enlarged view of a cross-sectional view of G_G of FIG. 18.

[55] 图 20是本发明之含生长因子的生物诱导型人体腔管代用品的结构示意图。 20 is a schematic view showing the structure of a growth factor-containing biologically induced human body tube substitute of the present invention.

[56] 图 21是图 20的 B— B的剖视图的放大图。 Figure 21 is an enlarged view of a cross-sectional view taken along line B-B of Figure 20 .

[57] 图 22是本发明之含种子细胞的生物诱导型人体腔管代用品的结构示意图。 22 is a schematic view showing the structure of a biologically induced human body tube substitute containing seed cells of the present invention.

[58] 图 23是图 22的 H_H的剖视图的放大图。 23 is an enlarged view of a cross-sectional view of H_H of FIG. 22.

[59] 图 24是本发明之含种子细胞的生物诱导型人体腔管代用品的结构示意图。 [60] 图 25是图 24的 L_L的剖视图的放大图。 24 is a schematic view showing the structure of a biologically induced human body tube substitute containing seed cells of the present invention. 25 is an enlarged view of a cross-sectional view of L_L of FIG. 24.

[61] 图 26是本发明之单喇叭***生长因子的生物诱导型人体腔管代用品的刚植入食管吋的工作原理图。 Figure 26 is a schematic diagram showing the operation of a freshly implanted esophageal fistula of a bio-inducible human lumen tube containing a growth factor in a single bell mouth of the present invention.

[62] 图 27是图 26的诱导出新生食管吋的工作原理图。 Figure 27 is a schematic diagram of the operation of the neonatal esophageal fistula induced by Figure 26.

[63] 图 28是本发明之含生长因子的生物诱导型人体腔管代用品的刚植入气管吋的工作原理图。 Figure 28 is a schematic view showing the operation of the growth factor-containing bioinducible human body tube substitute of the present invention.

[64] 图 29是图 28的诱导出新生气管吋的工作原理图。 [64] Figure 29 is a schematic diagram of the operation of the new angry tube raft of Figure 28.

[65] 图 30是本发明之生物诱导型人体腔管代用品的刚植入尿道吋的工作原理图。 Figure 30 is a schematic diagram showing the working principle of the newly implanted urethral fistula of the biologically induced human lumen tube substitute of the present invention.

[66] 图 31是图 30的诱导出新生尿道吋的工作原理图。 Figure 31 is a schematic diagram of the operation of Figure 30 for inducing neonatal urethral fistula.

[67] 上述图中， 1为支撑管， 2为连接件， 3为可吸收涂层， 4为本发明之生物诱导型人体腔管代用品， 5为回收线， 6为防返流装置， 7为缝合线， 8为人体正常腔管断端， 9为新生腔管， 11为支撑架， 12为柔性材料膜， 31为生物降解材料， 32为生长因子， 33为种子细胞， [67] In the above figure, 1 is a support tube, 2 is a connecting member, 3 is an absorbable coating, 4 is a biologically induced human body tube substitute of the present invention, 5 is a recycling line, and 6 is an anti-backflow device. 7 is suture, 8 is the normal lumen of the human body, 9 is the new lumen, 11 is the support frame, 12 is the flexible material membrane, 31 is the biodegradable material, 32 is the growth factor, 33 is the seed cell,

81为近端正常食管断端， 82为远端正常食管断端， 83为近端正常气管断端， 84 为远端正常气管断端， 85为近端正常尿道断端， 86为远端正常尿道断端， 90为新生腔管的狭窄部， 91为新生食管， 92为新生气管， 93为新生尿道， 111为支撑架的 U型节， 112为支撑架的金属丝头， 121为热合处。 81 is the proximal normal esophageal end, 82 is the distal normal esophageal end, 83 is the proximal normal tracheal stump, 84 is the distal normal trachea stump, 85 is the proximal normal urethral stump, 86 is the distal normal Urethral stump, 90 is the stenosis of the new lumen, 91 is the new esophagus, 92 is the new irritated tube, 93 is the new urethra, 111 is the U-section of the support frame, 112 is the wire head of the support frame, 121 is the heat seal .

本发明的最佳实施方式 BEST MODE FOR CARRYING OUT THE INVENTION

[68] 实施例 1 : 本发明之单丝编制的生物诱导型人体腔管代用品 [68] Example 1: Bioinducible human body tube substitute prepared by monofilament of the present invention

[69] 釆用恢复温度为 15°C直径为 0.25mm的镍钛形状记忆合金（ Nitinol合金）丝 [69] Nickel-titanium shape memory alloy (Nitinol alloy) wire with a recovery temperature of 15 ° C and a diameter of 0.25 mm

，在模具中编织支撑管的支撑架 11，然后在模具中进行定型热处理，使其在恢复温度以上为网状结构的圆柱管形，抛光、清洗后，即得到了本发明所述的支撑架 11，参考图 1 。 Bracing the support frame 11 of the support tube in the mold, and then performing a shaping heat treatment in the mold to make it a cylindrical tube shape having a mesh structure above the recovery temperature. After polishing and cleaning, the support frame according to the present invention is obtained. 11, refer to Figure 1.

[70] 在图 1中，所述支撑架 11，通过单丝弯曲形成的 U型节 111，一个套一个的连接在一起，形成可拆卸的支架，即拉动上端的金属丝头 112，将 U型节 111 拉直，就可以逐个地拆除 U型节 111，从而拆除整个支撑架 11，变成一根单丝。这种通过单丝编织、以 U型节 111的可拆卸的支撑架 11沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋径向支撑力大，在组织中容易定位，不容易滑脱。特别适合于用于食管、气管的有蠕动的腔管重建吋的支撑。 In FIG. 1, the support frame 11 is formed by a U-shaped section 111 formed by bending a single wire, and one set is connected together to form a detachable bracket, that is, pulling the upper end of the wire head 112, U When the section 111 is straightened, the U-shaped section 111 can be removed one by one, thereby removing the entire support frame 11 and becoming a monofilament. The detachable support frame 11 which is woven by the monofilament and has the U-shaped section 111 can be freely stretched and contracted in the longitudinal direction to a certain extent, and can be freely bent and swayed in the radial direction, and the radial support force is large, in the tissue. Easy to position, not easy to slip off. It is especially suitable for the reconstruction of the sacral canal for the esophagus and trachea.

[71] 在医用硅胶覆膜设备中，将制得的上述支撑管 11安装在专用模具中，按照医用硅胶的通用工艺对支撑架 11覆膜，得到被柔性材料膜 12，即医用硅胶膜，包覆的支撑架 11的覆膜网状支架管体，也就是得到了本发明所述的支撑管 1 ，参考图 9。 [71] In the medical silica gel laminating apparatus, the above-mentioned support tube 11 is installed in a special mold, and the support frame 11 is coated according to the general process of the medical silica gel to obtain the flexible material film 12, that is, the medical silicone film. The coated mesh stent body of the coated support frame 11, that is, the support tube 1 of the present invention is obtained, with reference to FIG.

[72] 釆用针织的涤纶环作为连接件 2，用手术缝合线 7将连接件 2缝合固定在支撑管 1的端部，离端部的距离为 10mm。清洗、灭菌，等待喷涂可吸收涂层 3 ，参考图 2。 [72] Using a knitted polyester ring as the connector 2, the connector 2 is sutured to the end of the support tube 1 with a surgical suture 7, and the distance from the end is 10 mm. Wash, sterilize, and wait for the spray to absorb the coating 3 , refer to Figure 2.

[73] 将包含有生物降解材料 31的液体，如明胶液、胶原液，注入超声雾化喷涂装置中，一边旋转支撑管体 1，一边喷涂含生物降解材料 31的液体，同吋进行冷冻干燥处理，即可在支撑管 1的外壁上制造可吸收涂层 3。做好可吸收涂层 3 ，包装后用 γ射线辐照灭菌或用环氧乙垸熏蒸灭菌，即得到了本发明之生物诱导型人体腔管代用品 4，参考图 2和图 3。 [73] The liquid containing the biodegradable material 31, such as gelatin solution or collagen solution, is injected into the ultrasonic atomizing spraying device, and while rotating the supporting tube body 1, the liquid containing the biodegradable material 31 is sprayed, and the same is freeze-dried. The absorbent coating 3 can be produced on the outer wall of the support tube 1 by treatment. The absorbable coating 3 is prepared, and after packaging, it is sterilized by gamma irradiation or fumigation with epoxy oxime, and the bio-inducible human body tube substitute of the present invention is obtained 4, referring to Figs. 2 and 3.

[74] 在图 2和图 3中，展示了本发明之生物诱导型人体腔管代用品的基本结构，本发明之生物诱导型人体腔管代用品由支撑管 1、连接件 2和可吸收涂层 3组成，其中，支撑管 1又由支撑架 11和柔性材料膜 12组成。可吸收涂层 3涂覆在支撑管 1的外壁上，连接件 2设置于支撑管 1的两端，距离端部约 10mm。柔性材料膜 12附着在支撑架 11上。 In Fig. 2 and Fig. 3, the basic structure of the biologically induced human body tube substitute of the present invention is shown, and the biologically induced human body tube substitute of the present invention is supported by the support tube 1, the connecting member 2 and the absorbable body. The composition of the coating 3, wherein the support tube 1 is in turn composed of a support frame 11 and a flexible material film 12. The absorbable coating 3 is coated on the outer wall of the support tube 1, and the connecting member 2 is disposed at both ends of the support tube 1, about 10 mm from the end. The flexible material film 12 is attached to the support frame 11.

[75] 上述可降解生物材料 31，至少选自：乳酸、聚羟基乙酸、聚羟基丁酯、聚酸酐、聚己内酯、聚偶磷氮、聚磷腈、聚氨基酸、假聚氨基酸、聚原酸酯、聚酯尿垸、聚三亚甲基碳酸酯、聚乙二醇、聚对二氧六环酮、壳聚糖、胶原、明胶、透明质酸、甲壳素、海藻酸盐、藻酸钙凝胶、脱细胞基质、生物玻璃，及其共聚物或混合物。 [75] The above degradable biomaterial 31, at least selected from the group consisting of: lactic acid, polyglycolic acid, polyhydroxybutyl ester, polyanhydride, polycaprolactone, polyphosphazene, polyphosphazene, polyamino acid, pseudopolyamino acid, poly Orthoester, polyester urethane, polytrimethylene carbonate, polyethylene glycol, polydioxanone, chitosan, collagen, gelatin, hyaluronic acid, chitin, alginate, alginic acid Calcium gel, acellular matrix, bioglass, and copolymers or mixtures thereof.

[76] 在本实施例中，柔性材料膜 12还可以至少选自：聚氨酯、聚四氟乙烯，各种纤维增强性医用柔性薄膜等材料。但依据材料的性质不同，其制造工艺也有所不同。如，柔性材料膜 12釆用聚四氟乙烯吋，可以使用缝合的方法将聚四氟乙烯的柔性材料膜 12固定在支撑架 11上，参考图 4至 6。 [77] 在图 4中，展示了柔性材料膜 12附着在支撑架 11的一种具体方式， gP: 柔性材料膜 12附着在支撑架 11的外壁。将柔性材料膜 12，如聚四氟乙烯薄膜，置于支撑架 11的外壁，并用手术缝合线 7将柔性材料膜 12可拆卸地缝合在支撑架 11的不容易变形部分，如支撑架 11金属丝的直线段，支撑架 11上的 U型节 111可以沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋实现了柔性材料膜 12不过分约束支撑架 11的运动，方便植入的支撑管 1适应食管或气管的蠕动，防止吻合口瘘和脱管。这种膜在外，而支架在内的结构，比较适合于气管的诱导生成，可以避免膜意外脱落而造成堵塞气管的风险，并方便在气管镜下拆除本发明之生物诱导型人体腔管代用品。拆除本发明之生物诱导型人体腔管代用品，仅需在气管镜下的直视下，先拆除缝合固定柔性材料膜 12的手术缝合线 7，再用手术钳夹住支撑架 11的金属丝头 112，用力拉动金属丝， U型节 111变直，即可方便拆除支撑架 11，同吋还可以取出连接件 2。 [76] In this embodiment, the flexible material film 12 may also be at least selected from the group consisting of polyurethane, polytetrafluoroethylene, various fiber-reinforced medical flexible films, and the like. However, depending on the nature of the material, the manufacturing process is different. For example, the flexible material film 12 is made of polytetrafluoroethylene, and the flexible material film 12 of the polytetrafluoroethylene can be fixed to the support frame 11 by sewing, see FIGS. 4 to 6. In FIG. 4, a specific manner in which the flexible material film 12 is attached to the support frame 11 is shown, and the gP: flexible material film 12 is attached to the outer wall of the support frame 11. A flexible material film 12, such as a polytetrafluoroethylene film, is placed on the outer wall of the support frame 11, and the flexible material film 12 is detachably sewn to the non-deformable portion of the support frame 11 by the surgical suture 7, such as the metal of the support frame 11. The straight section of the wire, the U-shaped section 111 on the support frame 11 can be freely stretched and contracted to some extent in the longitudinal direction, and can be freely bent and swayed in the radial direction, and the flexible material film 12 is not excessively constrained by the support frame 11. The movable, easy-to-implant support tube 1 accommodates the peristalsis of the esophagus or trachea, preventing anastomotic leakage and detachment. The membrane is external, and the structure inside the stent is more suitable for the induced formation of the trachea, which can avoid the risk of clogging the trachea due to accidental detachment of the membrane, and facilitate the removal of the biologically induced human lumen tube substitute of the present invention under the bronchoscope. . The biologically inducible human body tube substitute of the present invention is removed, and only the surgical suture 7 for suturing and fixing the flexible material film 12 is removed under direct vision under the bronchoscope, and the wire of the support frame 11 is clamped by the surgical forceps. The head 112 pulls the wire hard, and the U-shaped section 111 is straightened, so that the support frame 11 can be easily removed, and the connector 2 can be taken out at the same time.

[78] 在图 5中，展示了柔性材料膜 12附着在支撑架 11的另外一种具体方式，即：柔性材料膜 12附着在支撑架 11的内壁上。将柔性材料膜 12，如聚四氟乙烯薄膜，置于支撑架 11的内壁，并用手术缝合线 7将柔性材料膜 12缝合在支撑架 11的不容易变形部分，如支撑架 11金属丝的直线段，支撑架 11上的 U型节 111可以沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋实现了柔性材料膜 12不过分约束支撑架 11的运动，方便植入的支撑管 1适应食管或气管的蠕动，防止吻合口瘘和脱管。这种膜在内，而支架在外的结构，内壁光滑，便于食物滑落，比较适合于食管的诱导生成。特别是如果釆用降解吋间大于 ₆个月的手术缝合线 7缝合固定吋，当植入体内 6个月后，新生腔管（如新生食管）诱导生成，而且上皮化和组织稳定后，手术缝合线 7降解，聚四氟乙烯薄膜制造的内膜，即柔性材料膜 12脱落，掉入胃中，可以自然排出或者在消化内镜下取出，同吋拉出金属丝头 112，可以拆除支撑架 11，仅在体内保留诱导出的新生腔管（如新生食管）。 In FIG. 5, another specific manner in which the flexible material film 12 is attached to the support frame 11 is shown, that is, the flexible material film 12 is attached to the inner wall of the support frame 11. A flexible material film 12, such as a polytetrafluoroethylene film, is placed on the inner wall of the support frame 11, and the flexible material film 12 is sewn to the non-deformable portion of the support frame 11 by the surgical suture 7, such as a straight line of the support frame 11 wire. In the segment, the U-shaped section 111 on the support frame 11 can be freely extended and contracted to some extent in the longitudinal direction, and can be freely bent and swayed in the radial direction, and the flexible material film 12 is not excessively constrained to support the movement of the support frame 11, which is convenient. The implanted support tube 1 is adapted to the peristalsis of the esophagus or trachea to prevent anastomotic leakage and decoupling. The film is inside, and the structure of the stent is outside, the inner wall is smooth, and the food is slipped, which is more suitable for the induction of esophagus. In particular, if the sputum is sutured with a surgical suture 7 that is more than ₆ months after deuteration, after 6 months of implantation, a new lumen (such as a neonatal esophagus) is induced, and after epithelialization and tissue stabilization, surgery The suture 7 is degraded, and the inner membrane made of the polytetrafluoroethylene film, that is, the flexible material film 12 falls off, falls into the stomach, can be naturally discharged or taken out under the digestive endoscope, and the wire head 112 is pulled out at the same time, and the support can be removed. Shelf 11 retains the induced neonatal lumen (such as the neonatal esophagus) only in vivo.

[79] 在图 6中，展示了柔性材料膜 12附着在支撑架 11的第三种具体方式， gP: 支撑架 11被 2层柔性材料膜 12包覆。釆用 0.4mm厚度的聚四氟乙烯薄膜作为柔性材料膜 12，将一层柔性材料膜 12置于支撑架 11的内壁，作为内膜；再将另一层柔性材料膜 12置于支撑架 11的外壁，作为外膜；然后用手术缝合线 7将内、外两层柔性材料膜 12同吋缝合在支撑架 11的不容易变形部分，如支撑架 11金属丝的直线段参考图 6，支撑架 11上的 U型节 111在两层柔性材料膜 12 之间形成的空间内可以沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋实现了柔性材料膜 12不过分约束支撑架 11的运动，方便植入的支撑管 1适应食管或气管的蠕动，防止吻合口瘘和脱管。 In FIG. 6, a third specific manner in which the flexible material film 12 is attached to the support frame 11 is shown, gP: The support frame 11 is covered by two layers of flexible material film 12.作为Use 0.4mm thick PTFE film as soft a film 12 of a material, a layer of flexible material film 12 is placed on the inner wall of the support frame 11 as an inner film; another layer of flexible material film 12 is placed on the outer wall of the support frame 11 as an outer film; 7 The inner and outer layers of the flexible material film 12 are sewn together in the non-deformable portion of the support frame 11, such as the straight line segment of the support frame 11 wire. Referring to FIG. 6, the U-shaped section 111 on the support frame 11 is flexible in two layers. The space formed between the material films 12 can be freely stretched and contracted to some extent in the longitudinal direction, and can be freely bent and swayed in the radial direction, and the flexible material film 12 is not excessively constrained to support the movement of the support frame 11, facilitating implantation. The support tube 1 adapts to the peristalsis of the esophagus or the trachea, preventing anastomotic leakage and decoupling.

[80] 而柔性材料膜 12釆用聚氨酯材料吋，则可以选择热合工艺将聚氨酯的柔性材料膜 12固定在支撑架 11上，参考图 7。 [80] While the flexible material film 12 is made of a polyurethane material, the polyurethane flexible film 12 can be fixed to the support frame 11 by a heat sealing process, as shown in Fig. 7.

[81] 在图 7中，展示了柔性材料膜 12附着在支撑架 11的第四种具体方式，即：支撑架 11被 2层柔性材料膜 12包覆，但内膜和外膜之间的固定方式与图 6展示的实施例不同，釆用了热合法。用 0.5mm厚度的聚氨脂薄膜作为柔性材料膜 12 ，将一层柔性材料膜 12置于支撑架 11的内壁，作为内膜；再将另一层柔性材料膜 12置于支撑架 11的外壁，作为外膜；然后将对应于支撑架 11的孔洞处的内、外两层柔性材料膜 12同吋热合在一起参考图 7，热合处为 121，支撑架 11 上的 U型节 111在两层柔性材料膜 12之间形成的空间内可以沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋实现了柔性材料膜 12不过分约束支撑架 11的运动，方便植入的支撑管 1适应食管或气管的蠕动，防止吻合口瘘和脱管。 In Fig. 7, a fourth specific manner in which the flexible material film 12 is attached to the support frame 11 is shown, that is, the support frame 11 is covered by two layers of the flexible material film 12, but between the inner and outer films. The fixing method is different from the embodiment shown in Fig. 6, and thermal law is employed. A 0.5 mm thick polyurethane film is used as the flexible material film 12, and a layer of the flexible material film 12 is placed on the inner wall of the support frame 11 as an inner film; and another layer of the flexible material film 12 is placed on the outer wall of the support frame 11. As the outer film; then the inner and outer two layers of flexible material film 12 corresponding to the holes of the support frame 11 are heat-sealed together with reference to FIG. 7, the heat sealing portion is 121, and the U-shaped joint 111 on the support frame 11 is in two The space formed between the layers of the flexible material film 12 can be freely stretched and contracted to some extent in the longitudinal direction, and can be freely bent and swayed in the radial direction, so that the flexible material film 12 does not unduly restrain the movement of the support frame 11, which is convenient. The implanted support tube 1 is adapted to the peristalsis of the esophagus or trachea to prevent anastomotic leakage and decoupling.

[82] 依据不同部位的不同技术要求，包覆支撑架 11的柔性材料膜 12在支撑管 1的不同部位可以釆用不同材料，如，在支撑管 1的中部，新生食管的疤痕组织收缩比较严重，柔性材料膜 12要求有比较好的强度，同吋支撑管 1的内膜要求光滑，方便食物滑落，掉入胃中，故可以选择强度高抗腐蚀性能好的聚四氟乙烯薄膜。而在支撑管 1的两个端部，其外与正常的食管断端吻合，要尽可能分散金属丝的支撑力，防止应力集中，而对食管过度刺激形成肉牙组织，故在聚四氟乙烯薄膜外，还可以用医用硅胶包覆，制造一层较后的柔性材料膜 12来分散金属丝的支撑力，防止肉牙组织增生。形成了柔性材料膜 12在支撑架 11的多材料多层结构的附着方式，参考图 8。 [83] 在图 8中，展示了用 2种不同柔性材料制造柔性材料膜 12来包覆支撑架 11 吋的结构示意图，即展示了柔性材料膜 12附着在支撑架 11的第五种具体方式。依据不同部位的不同技术要求，包覆支撑架 11的柔性材料膜 12在支撑管 1 的不同部位可以釆用不同材料。以诱导生成新生食管为例，在支撑管 1的中部，新生食管的疤痕组织收缩比较严重，柔性材料膜 12要求有比较好的强度，同吋支撑管 1的内膜要求光滑，方便食物滑落，掉入胃中，故可以选择强度高抗腐蚀性能好的聚四氟乙烯薄膜。而在支撑管 1的两个端部，其外与正常的食管断端吻合，要尽可能分散金属丝的支撑力，防止应力集中，而对食管过度刺激形成肉牙组织，故在聚四氟乙烯薄膜外，还可以用医用硅胶包覆，制造一层较后的柔性材料膜 12来分散金属丝的支撑力，防止肉牙组织增生。釆用这种多层膜的结构，医用硅胶包覆并不影响支撑架 11的运动，支撑架 11上的 U型节 111在两层柔性材料膜 12之间形成的空间内可以沿纵向在一定程度上可以自由伸缩，而沿径向可以自由弯曲、晃动，同吋实现了柔性材料膜 12不过分约束支撑架 11的运动，方便植入的支撑管 1适应食管或气管的蠕动，防止吻合口瘘和脱管。 [82] According to different technical requirements of different parts, the flexible material film 12 covering the support frame 11 can use different materials in different parts of the support tube 1, for example, in the middle of the support tube 1, the contraction of the scar tissue of the new esophagus is compared. Seriously, the flexible material film 12 is required to have relatively good strength, and the inner film of the same support tube 1 is required to be smooth, and it is convenient for the food to slip down and fall into the stomach, so that a polytetrafluoroethylene film with high strength and good corrosion resistance can be selected. At the two ends of the support tube 1, the outer part of the support tube 1 is matched with the normal end of the esophagus, and the support force of the wire should be dispersed as much as possible to prevent stress concentration, and excessive stimulation of the esophagus to form the meat tooth tissue, so in the PTFE In addition to the vinyl film, it can also be coated with medical silica gel to form a later layer of flexible material film 12 to disperse the supporting force of the wire to prevent proliferation of the dental tissue. The manner of attachment of the flexible material film 12 to the multi-material multilayer structure of the support frame 11 is formed, with reference to FIG. [83] In FIG. 8, a schematic view showing the structure of the flexible material film 12 for covering the support frame 11 by using two different flexible materials is shown, that is, the fifth specific manner in which the flexible material film 12 is attached to the support frame 11 is shown. . Depending on the technical requirements of the different parts, the flexible material film 12 covering the support frame 11 can be made of different materials in different parts of the support tube 1. Taking the induced neonatal esophagus as an example, in the middle of the support tube 1, the contraction of the scar tissue of the new esophagus is serious, and the flexible material membrane 12 requires relatively good strength, and the inner membrane of the same support tube 1 is required to be smooth, and the food is slippery. Dropped into the stomach, you can choose a high strength and corrosion resistance Teflon film. At the two ends of the support tube 1, the outer part of the support tube 1 is matched with the normal end of the esophagus, and the support force of the wire should be dispersed as much as possible to prevent stress concentration, and excessive stimulation of the esophagus to form the meat tooth tissue, so in the PTFE In addition to the vinyl film, it can also be coated with medical silica gel to form a later layer of flexible material film 12 to disperse the supporting force of the wire to prevent proliferation of the dental tissue. With the structure of the multilayer film, the medical silicone coating does not affect the movement of the support frame 11, and the U-shaped section 111 on the support frame 11 can be longitudinally defined in the space formed between the two flexible material films 12. The degree can be freely stretched, and can be freely bent and swayed in the radial direction. Simultaneously, the flexible material film 12 does not unduly restrain the movement of the support frame 11, and the implanted support tube 1 can be adapted to the peristalsis of the esophagus or the trachea to prevent the anastomosis.瘘 and take off.

[84] 在图 9中，展示了用柔性材料包覆支撑架 11来制造柔性材料膜 12的技术方案，即展示了柔性材料膜 12附着在支撑架 11的第六种具体方式。选择高强度医用硅胶，按照医用硅胶通用工艺，直接包覆支撑架 11，即得到了支撑管 1 。但是，这种直接包覆工艺，支撑架 11上的 U型节 111镶嵌在柔性材料膜 12中间，支撑架 11的运动在一定程度上受到柔性材料膜 12的约束，其柔顺性和适应食管或气管的蠕动的能力，不如前五种方式好。 In Fig. 9, a technical solution for manufacturing a flexible material film 12 by covering the support frame 11 with a flexible material is shown, i.e., a sixth specific manner in which the flexible material film 12 is attached to the support frame 11 is shown. The high-strength medical silica gel is selected, and the support tube 1 is obtained by directly coating the support frame 11 according to the general process of medical silica gel. However, in this direct coating process, the U-shaped section 111 on the support frame 11 is embedded in the middle of the flexible material film 12, and the movement of the support frame 11 is restrained to some extent by the flexible material film 12, which is flexible and adapted to the esophagus or The ability of the trachea to move is not as good as the first five.

[85] 制造支撑架 11的材料，还可以至少选自： β钛合金、医用不锈钢、医用锆合金，医用锆铌合金、医用钛锆铌合金、无镍钛基形状记忆合金、弹性高分子材料等弹性材料。材料的弹性越好，其与人体食管、或气管等人体腔管的吻合性越好，越不容易发生吻合口瘘。 [85] The material for manufacturing the support frame 11 may also be at least selected from the group consisting of: β titanium alloy, medical stainless steel, medical zirconium alloy, medical zirconium-niobium alloy, medical titanium zirconium-niobium alloy, nickel-free titanium-based shape memory alloy, elastic polymer material. Elastic materials. The better the elasticity of the material, the better the fit with the human lumen of the human esophagus, or the trachea, and the less likely the anastomotic leakage occurs.

[86] 制造连接件 2的材料，还可以至少选自：聚乙烯、聚丙烯、聚氨酯、聚四氟乙烯等材料，要求生物相容性好，强度高，质量轻。 [86] The material of the connecting member 2 can also be at least selected from the group consisting of polyethylene, polypropylene, polyurethane, polytetrafluoroethylene, etc., requiring good biocompatibility, high strength and light weight.

[87] 实施例 2 : 本发明之交叉网格生物诱导型人体腔管代用品 [88] 本实施例的制造方法与实施例 1基本相同，其特点在于支撑架 11的制造吋的编织方式釆用了交叉网格的编织方式，参考图 10至图 11 。 [87] Example 2: Cross-grid biologically induced human lumen tube substitute of the present invention The manufacturing method of the present embodiment is basically the same as that of the first embodiment, and is characterized in that the knitting method of manufacturing the crucible of the support frame 11 uses a cross-grid weaving method, with reference to FIGS. 10 to 11.

[89] 在图 10和图 11中，本实施例中支撑架 11釆用了交叉网格的编织方式，其柔性材料膜 12附着在支撑架 11的方式也可以有类似于图 2至图 9所展示的多种具体方式。 In FIG. 10 and FIG. 11 , in this embodiment, the support frame 11 is woven by a cross grid, and the flexible material film 12 is attached to the support frame 11 in a manner similar to that of FIGS. 2 to 9 . A variety of specific ways to show.

[90] 实施例 3：本发明之带单喇叭口的交叉网格生物诱导型人体腔管代用品 [90] Example 3: The cross-grid bioinducing human body tube substitute with a single bell mouth of the present invention

[91] 本实施例的制造方法与实施例 1基本相同，其特点在于支撑架 11的制造吋的编织方式釆用了带单喇叭口的交叉网格的编织方式；此外，覆医用硅胶膜吋，同吋在支撑管 1的远端制造了 3瓣式的防返流装置，参考图 12至图 13。 [91] The manufacturing method of the embodiment is basically the same as that of the first embodiment, and is characterized in that the knitting method of manufacturing the crucible of the support frame 11 uses a cross-grid weaving method with a single bell mouth; At the same time, a 3-valve anti-backflow device is manufactured at the distal end of the support tube 1, see Figs. 12 to 13.

[92] 如图 12和图 13所示，本实施例中支撑架 11釆用了单喇叭***叉网格的编织方式，其柔性材料膜 12附着在支撑架 11的方式也可以有类似于图 2至图 9所展示的多种具体方式，此外，在支撑管 1的下端，还设置了三瓣式的防返流装置 6。 As shown in FIG. 12 and FIG. 13 , in the embodiment, the support frame 11 is woven by a single bell cross-grid, and the flexible material film 12 is attached to the support frame 11 in a similar manner. 2 to various specific modes shown in Fig. 9, in addition, at the lower end of the support tube 1, a three-lobed anti-backflow device 6 is also provided.

[93] 实施例 4 : 本发明之螺旋结构的生物诱导型人体腔管代用品 [93] Example 4: Biologically induced human lumen tube substitute of the spiral structure of the present invention

[94] 本实施例的制造方法与实施例 1基本相同，其特点在于支撑架 11的釆用了单丝绕制的螺旋弹簧结构来制造，参考图 14至图 15。 The manufacturing method of this embodiment is basically the same as that of the embodiment 1, and is characterized in that the crucible of the support frame 11 is manufactured by a coil spring structure of a single wire, with reference to Figs. 14 to 15 .

[95] 如图 14和图 15所示，本发明所述的支撑架 11釆用螺旋弹簧结构，由单丝绕制而成，方便拆卸。 As shown in Fig. 14 and Fig. 15, the support frame 11 of the present invention is formed by a coil spring structure and is wound by a single wire for easy disassembly.

[96] 实施例 5 : 本发明之激光雕刻的生物诱导型人体腔管代用品 [96] Example 5: Laser-engraved biologically induced human body tube substitute of the present invention

[97] 本实施例的制造方法与实施例 1基本相同，其特点在于支撑架 11的釆用了薄壁管经过激光雕刻形成的网状结构支架来制造，参考图 16至图 17。 The manufacturing method of the present embodiment is basically the same as that of the embodiment 1, and is characterized in that the cymbal of the support frame 11 is manufactured by using a mesh structure bracket formed by laser engraving of a thin-walled tube, with reference to Figs. 16 to 17 .

[98] 实施例 6 : 本发明之激光雕刻的生物诱导型人体腔管代用品 [98] Example 6: Laser-engraved biologically induced human body tube substitute of the present invention

[99] 本实施例的制造方法与实施例 1基本相同，其特点在于支撑管 1的外壁，无论是端部还是中间部分都涂覆了可吸收涂层 3，此外，还在支撑管 1近端设置了能将支撑管 1近端开口收拢的回收线，方便在必要吋将支撑管 1取出体外，参考图 18至图 19。 [99] The manufacturing method of the present embodiment is basically the same as that of Embodiment 1, and is characterized in that the outer wall of the support tube 1 is coated with the absorbable coating 3 both at the end portion and the intermediate portion, and further, the support tube 1 is also near The end is provided with a recovery line capable of closing the proximal end opening of the support tube 1, so that the support tube 1 can be taken out of the body if necessary, referring to Figs. 18 to 19.

[100] 如图 18和图 19所示，可吸收涂层 3覆盖整个支撑管 1的外壁，而且在支撑管 1的近端，即上端，设置了能将支撑管 1的近端开口收拢的回收线 5，方便将支撑管 1取出。 [100] As shown in Figs. 18 and 19, the absorbable coating 3 covers the entire outer wall of the support tube 1, and at the proximal end of the support tube 1, i.e., the upper end, a proximal end opening of the support tube 1 is provided. Recycling line 5, convenient to support The support tube 1 is taken out.

[101] 实施例 7 : 本发明之含生长因子的生物诱导型人体腔管代用品 Example 7: Growth factor-containing biologically induced human body tube substitute of the present invention

[102] 本实施例的支撑管 1可以参考实施例 1的方法制备。 The support tube 1 of the present embodiment can be prepared by referring to the method of Example 1.

[103] 釆用编织的涤纶环作为连接件 2，用手术缝合线 7将连接件 2缝合固定在支撑管 1的端部，离端部的距离为 15 mm。清洗、灭菌，等待喷涂可吸收涂层 3。 [103] Using a woven polyester ring as the connector 2, the connector 2 is sutured to the end of the support tube 1 with a surgical suture 7, with a distance of 15 mm from the end. Wash, sterilize, and wait for the spray to absorb the coating 3 .

[104] 将可吸收生物降解材料 31，如聚丙交酯 -乙二醇 -己内酯共聚物，与生长因子 32如转化生长因子 TGF-α , PDGF等，溶于合适的易挥发溶剂中，如丙酮，形成混悬液，配成浓度为 0.01〜 10 %的均匀涂层溶液，备用。 [104] dissolving the biodegradable material 31, such as a polylactide-ethylene glycol-caprolactone copolymer, with a growth factor 32 such as transforming growth factor TGF-α, PDGF, etc., in a suitable volatile solvent, Such as acetone, a suspension is formed, and a uniform coating solution having a concentration of 0.01 to 10% is prepared and used.

[105] 首先，将配制好的涂层溶液灌制于注射器中，调节超声波发生器功率为 0.1〜 5w、注射器中涂层溶液的注入速度为 0.001〜 0.1ml / min以及压缩气体压力为 0.2〜10psi _; 其次，将支撑管体装夹于特定夹具上，在程序软件界面下设定支架水平移动速度为 0 . 01〜lcm 7 s、支撑管体旋转速度为 10〜 350r 7 min、旋转方向、支撑管体运动往复次数为 1〜 200次、干燥气体压力为 0.2〜 lOpsi 排风***的排风速度 10〜 1000CFM ; 最后调用并启动喷涂程序，超声波发生器产生超声波，通过传感器传至微雾化喷嘴上，涂层溶液在注射泵的动力下由注射器通过管道输送至喷嘴的雾化面上，超声波将液体雾化成细小液滴，液滴在低速压缩气体的带动下飞向支撑管体 1表面，在支撑管体 1表面形成一层很薄的液体层，待液体层中有机溶剂挥发后，支撑管体 1表面沉积上一层很薄的含生长因子 32的可吸收涂层 3，其间支撑管体 1在喷嘴下方往复运动。 [105] First, the prepared coating solution is filled in a syringe, the ultrasonic generator power is adjusted to 0.1 to 5w, the injection rate of the coating solution in the syringe is 0.001 to 0.1 ml / min, and the compressed gas pressure is 0.2 to 10 psi. _; secondly, clamping the support tube on a particular jig, the bracket is set to 0 in the horizontal moving speed of the software interface 01~lcm 7 s, the rotational speed of the support tube 10~ 350r 7 min, the rotational direction of the support. The number of reciprocating movements of the pipe body is 1 to 200 times, the pressure of the drying gas is 0.2 to lOpsi, and the exhausting speed of the exhaust system is 10 to 1000 CFM. Finally, the spraying process is called and started, and the ultrasonic generator generates ultrasonic waves, which are transmitted to the micro atomizing nozzle through the sensor. Above, the coating solution is conveyed by a syringe to the atomizing surface of the nozzle by a syringe pump, and the ultrasonic wave atomizes the liquid into small droplets, and the droplets fly toward the surface of the supporting tube body 1 under the action of the low-speed compressed gas. A thin liquid layer is formed on the surface of the support pipe body 1. After the organic solvent in the liquid layer is volatilized, a thin layer of the surface of the support pipe body 1 is deposited. Growth factor absorbable coating 332, during which the support tube 1 below the nozzle reciprocates.

[106] 将喷涂后的支撑管体 1进行干燥处理，即可在支撑管 1的外壁上制造可吸收涂层 3。做好可吸收涂层 3，干燥完毕包装后用 γ射线辐照灭菌或用环氧乙垸熏蒸灭菌，即得到了本发明之生物诱导型人体腔管代用品。 [106] The sprayed support tube 1 is dried to form an absorbable coating 3 on the outer wall of the support tube 1. The absorbable coating 3 is prepared, and after drying and packaging, it is sterilized by γ-ray irradiation or sterilized by epoxy oxime, and the biologically induced human cavity tube substitute of the present invention is obtained.

[107] 本实施例的特点在于可吸收涂层 3中含有生长因子 32。生长因子 32可以是弥散分布于可吸收涂层 3中，也可以是被生物降解材料 31包覆后分布在可吸收涂层 3，还可以是分层涂覆在可吸收涂层 3中，或浸染或吸附在可吸收涂层 3中。所述生长因子 32至少选自：血小板类生长因子（血小板来源生长因子 PDGF ；骨肉瘤来源生长因子 ODGF ) 、表皮生长因子类（表皮生长因子， EGF、转化生长因子， TGF-α和 TGF-β ) 、成纤维细胞生长因子（ FGF、 α-FGF、 β-FGF ) 、类胰岛素生长因子（IGF-I、 IGF-Π ) 、神经生长因子（ NGF ) 、白细胞介素类生长因子（IL-1、 IL-2、 IL-3等）、红细胞生长素（ EPO ) 、集落刺激因子（CSF ) ，及其混合物，参考图 20、图 21。 [107] This embodiment is characterized in that the absorbable coating 3 contains the growth factor 32. The growth factor 32 may be dispersed in the absorbable coating 3, may be distributed in the absorbable coating 3 after being coated with the biodegradable material 31, or may be layered in the absorbable coating 3, or Dip or adsorb in the absorbable coating 3. The growth factor 32 is at least selected from the group consisting of: platelet growth factor (platelet-derived growth factor PDGF; osteosarcoma-derived growth factor ODGF), epidermal growth factor (EGF, EGF, transforming growth factor, TGF-α, and TGF-β) ), fibroblast growth factor (FGF, α-FGF, β-FGF), insulin-like growth factor (IGF-I, IGF-Π), nerve growth factor (NGF), interleukin growth factor (IL-1, IL-2, IL-3, etc.), erythrocyte growth factor (EPO), colony stimulating factor (CSF), and mixtures thereof, see Figure 20, Figure 21.

[108] 此外，本实施例的喇叭口上设置了回收线 5，方便取出支撑管 1。 Further, a recovery line 5 is provided on the bell mouth of the embodiment to facilitate the removal of the support tube 1.

[109] 实施例 8 : 本发明之含种子细胞的生物诱导型人体腔管代用品 [109] Example 8: Biologically inducible human body tube substitute for seed-containing cells of the present invention

[110] 本实施例的支撑管 1可以参考实施例 1的方法制备。 The support tube 1 of the present embodiment can be prepared by referring to the method of Example 1.

[111] 釆用编织的涤纶环作为连接件 2，用手术缝合线 7将连接件 2缝合固定在支撑管 1的端部，离端部的距离为 10mm。清洗、灭菌，等待喷涂可吸收涂层 3。 [111] A braided polyester ring is used as the connecting member 2, and the connecting member 2 is sutured and fixed to the end of the support tube 1 by a surgical suture 7, and the distance from the end portion is 10 mm. Wash, sterilize, and wait for the spray to absorb the coating 3 .

[112] 将可吸收生物降解材料 31，如聚丙交酯-乙二醇共聚物，与生物活性玻璃溶于合适的易挥发溶剂中，如二次蒸馏水 +丙酮，经超声分散形成混悬液或乳液，配成浓度为 0.01〜 10 %的均匀涂层溶液，备用。 [112] dissolving a biodegradable material 31, such as a polylactide-ethylene glycol copolymer, with a bioactive glass in a suitable volatile solvent, such as double distilled water + acetone, dispersed by ultrasonication to form a suspension or The emulsion is formulated into a uniform coating solution with a concentration of 0.01 to 10%, and is reserved.

[113] 将聚丙交酯-乙二醇共聚物 /生物活性玻璃溶液注入超声雾化喷涂装置中，进行喷涂。釆用一边旋转支撑管体 1，一边喷涂。同吋进行冷冻干燥处理，即可在支撑管 1的外壁上制造可吸收涂层 3。做好可吸收涂层 3，包装后用 γ射线辐照灭菌或用环氧乙垸熏蒸灭菌，待用。 [113] A polylactide-ethylene glycol copolymer/bioactive glass solution was injected into an ultrasonic atomizing spray apparatus for spraying.喷涂 Spray while supporting the tube body 1 while rotating. The freeze-drying treatment is carried out to produce an absorbable coating 3 on the outer wall of the support tube 1. Do a good absorption of the coating 3, packaged and sterilized by gamma irradiation or fumigated with epoxy acetonitrile.

[114] 床使用前，将种子细胞 33悬液接种到预先用 PBS缓冲溶液处理好的上述制备的带可吸收涂层 3的支撑管 1，于 37 °C、 5 % C0₂培养箱中进行培养，使细胞和可吸收涂层 3进一步结合。 4h后小心加入 K-SFM培养基，于 37 °C、 5 % C0₂培养箱中继续培养。经所需要培养吋间的培养后，得到体外培养的种子细胞 33-带可吸收涂层 3的支撑管 1复合物，即得到了本发明之生物诱导型人体腔管代用品，即可供在临床手术使用。 [114] Before use of the bed, the seed cell 33 suspension was inoculated into the support tube 1 with the absorbable coating 3 prepared in advance prepared by the PBS buffer solution, and was carried out in a 37 ° C, 5 % C0 ₂ incubator. The cells are further combined with the absorbable coating 3. After 4 h, the K-SFM medium was carefully added, and the culture was continued at 37 ° C in a 5 % C0 ₂ incubator. After the culture of the culture medium is required, the seed cell 33 in vitro is cultured, and the support tube 1 composite with the absorbable coating 3 is obtained, thereby obtaining the biologically induced human body tube substitute of the present invention, that is, Clinical use.

[115] 本实施例的特点在于可吸收涂层 3中含有种子细胞 33。种子细胞 33可以是弥散分布于可吸收涂层 3中，也可以是被生物降解材料 31包覆后分布在可吸收涂层 3，还可以是分层涂覆在可吸收涂层 3中，或浸染或吸附在可吸收涂层 3中。本实施例所述种子细胞 33至少选自：自体食管黏膜上皮细胞、自体骨髓间干细胞、同种异体骨髓间干细胞、胚胎干细胞，及其混合物。要按照具体的 II：床用途来选择具体的种子细胞 33，参考图 11、图 23。 The present embodiment is characterized in that the absorbable coating 3 contains seed cells 33. The seed cells 33 may be dispersedly distributed in the absorbable coating 3, may be distributed in the absorbable coating 3 after being coated with the biodegradable material 31, or may be layered in the absorbable coating 3, or Dip or adsorb in the absorbable coating 3. The seed cells 33 of the present embodiment are at least selected from the group consisting of: autologous esophageal mucosal epithelial cells, autologous mesenchymal stem cells, allogeneic bone marrow stem cells, embryonic stem cells, and mixtures thereof. The specific seed cells should be selected according to the specific II: bed use, refer to Figure 11, Figure 23.

[116] 实施例 9：本发明之含生长因子和种子细胞的生物诱导型人体腔管代用品 [117] 本实施例的支撑管 1可以参考实施例 1的方法制备。 [116] Example 9: Bioinducible human body tube substitute containing growth factor and seed cells of the present invention [117] The support tube 1 of the present embodiment can be prepared by referring to the method of Example 1.

[118] 釆用编织的涤纶环作为连接件 2，用手术缝合线 7将连接件 2缝合固定在支撑管 1的端部，离端部的距离为 10mm。清洗、灭菌，等待喷涂可吸收涂层 3。 [118] The woven polyester ring is used as the connecting member 2, and the connecting member 2 is sutured and fixed to the end of the support tube 1 by the surgical suture 7, and the distance from the end portion is 10 mm. Wash, sterilize, and wait for the spray to absorb the coating 3 .

[119] 将可吸收生物降解材料 31，如聚丙交酯-乙二醇共聚物，与脱细胞基质溶于合适的易挥发溶剂中，如二次蒸馏水 +丙酮中，经超声分散形成混悬液或乳液，配成浓度为 0.01〜 10 %的均匀涂层溶液，备用。另，釆用生理盐水配制表皮生长因子 I聚丙交酯 -乙二醇共聚物溶液。 [119] Dissolving the absorbable biodegradable material 31, such as polylactide-ethylene glycol copolymer, with the acellular matrix in a suitable volatile solvent, such as double distilled water + acetone, and ultrasonically dispersed to form a suspension. Or emulsion, formulated into a uniform coating solution with a concentration of 0.01 to 10%, ready for use. In addition, a skin growth factor I polylactide-ethylene glycol copolymer solution was prepared using physiological saline.

[120] 将聚丙交酯 -乙二醇共聚物 I脱细胞基质溶液及表皮生长因子 I聚丙交酯 -乙二醇共聚物溶液注入超声雾化喷涂装置中，釆用双液进料模式，进行双液喷涂。釆用一边旋转支撑管体 1 ，一边喷涂聚丙交酯-乙二醇共聚物，与脱细胞基质溶液；同吋另一喷嘴喷涂表皮生长因子 /聚丙交酯 -乙二醇共聚物溶液。同吋进行冷冻干燥处理，即可在支撑管 1的外壁上制造可吸收涂层 3。做好可吸收涂层 3中含有生长因子 32，包装后用 γ射线辐照灭菌或用环氧乙垸熏蒸灭菌，待用。 [120] Injecting a polylactide-ethylene glycol copolymer I acellular matrix solution and an epidermal growth factor I polylactide-ethylene glycol copolymer solution into an ultrasonic atomizing spraying device, and performing a two-liquid feeding mode Two-liquid spraying.旋转 Rotate the support tube 1 while spraying the polylactide-ethylene glycol copolymer with the acellular matrix solution; and spray the epidermal growth factor/polylactide-ethylene glycol copolymer solution on the other nozzle. The lyophilized treatment is carried out to produce an absorbable coating 3 on the outer wall of the support tube 1. Do a good absorption of the coating 3 contains growth factor 32, packaged and sterilized by gamma irradiation or fumigated with epoxy oxime, ready for use.

[121] 临床使用前，将种子细胞 33悬液接种到预先用 PBS缓冲溶液处理好的上述制备的含有生长因子 32的带可吸收涂层 3的支撑管 1，于 37 °C、 5 %。0₂培养箱中进行培养，使种子细胞 33和带可吸收涂层 3的支撑管 1进一步结合。 4h后小心加入 K-SFM培养基， 37 °C、 5 % C0₂培养箱中继续培养。经所需要培养吋间的培养后，得到体外培养的种子细胞 33-含有生长因子 32的带可吸收涂层 3的支撑管 1复合物，即得到了本发明之生物诱导型人体腔管代用品，即可供临床手术使用，参考图 24、图 25。 [121] Prior to clinical use, the seed cell 33 suspension was inoculated to the support tube 1 with the growth factor 32 prepared with the absorbable coating 3 prepared in advance with PBS buffer solution at 37 ° C, 5 %. The culture was carried out in a 0 ₂ incubator to further bind the seed cells 33 and the support tube 1 with the absorbable coating 3. After 4 h, the K-SFM medium was carefully added, and the culture was continued in a 37 ° C, 5 % C0 ₂ incubator. After the culture of the culture medium is required, the seed cell 33 in vitro is cultured, and the support tube 1 complex containing the growth factor 32 with the absorbable coating 3 is obtained, thereby obtaining the biologically induced human body tube substitute of the present invention. , that is, for clinical use, refer to Figure 24, Figure 25.

[122] 本实施例的特点在于可吸收涂层 3中同吋含有种子细胞 33和生长因子 32。种子细胞 33和生长因子 32可以是弥散分布于可吸收涂层 3中，也可以是被生物降解材料 31包覆后分布在可吸收涂层 3，还可以是分层涂覆在可吸收涂层 3中，或浸染或吸附在可吸收涂层 3中。所述种子细胞 33至少选自：自体食管黏膜上皮细胞、自体骨髓间干细胞、同种异体骨髓间干细胞、胚胎干细胞，及其混合物。要按照具体的临床用途来选择具体的种子细胞 33。所述生长因子 32 至少选自：血小板类生长因子（血小板来源生长因子， PDGF ; 骨肉瘤来源生长因子 ODGF ) 、表皮生长因子类（表皮生长因子， EGF、转化生长因子， TGFa和 TGFP ) 、成纤维细胞生长因子（ FGF、 aFGF、 FGF ) 、类胰岛素生长因子（IGF- I、 IGF- Π ) 、神经生长因子（NGF ) 、白细胞介素类生长因子（IL-1、 IL-2、 IL-3等）、红细胞生长素（ EPO ) 、集落刺激因子（ CSF[122] This embodiment is characterized in that the same layer in the absorbable coating 3 contains seed cells 33 and growth factors 32. The seed cells 33 and the growth factors 32 may be dispersed in the absorbable coating 3, may be distributed in the absorbable coating 3 after being coated with the biodegradable material 31, or may be layered on the absorbable coating. 3, or dip or adsorbed in the absorbable coating 3. The seed cells 33 are at least selected from the group consisting of: autologous esophageal mucosal epithelial cells, autologous bone marrow mesenchymal stem cells, allogeneic bone marrow mesenchymal stem cells, embryonic stem cells, and mixtures thereof. Specific seed cells 33 are selected for specific clinical use. The growth factor 32 is at least selected from the group consisting of: platelet growth factor (platelet derived growth factor, PDGF; osteosarcoma source) Long-factor ODGF), epidermal growth factor (EGF, EGF, transforming growth factor, TGFa and TGFP), fibroblast growth factor (FGF, aFGF, FGF), insulin-like growth factor (IGF-I, IGF-Π) ), nerve growth factor (NGF), interleukin growth factor (IL-1, IL-2, IL-3, etc.), erythrocyte growth factor (EPO), colony stimulating factor (CSF)

) ，及其混合物。 ), and mixtures thereof.

[123] 实施例 10 : 本发明之生物诱导型人体腔管代用品用于食道重建 [123] Example 10: The biologically induced human lumen tube substitute of the present invention is used for esophageal reconstruction

[124] 参考图 26和图 27，展示了一种用本发明之生物诱导型人体腔管代用品进行食管重建的方法。在切除病变的食管后，将近端，即靠近食管入口的正常食管断端 81，套在本发明之生物诱导型人体腔管代用品 4的近端上，将正常食管断端 81的黏膜置于本发明之生物诱导型人体腔管代用品 4的近端连接件 2之下，用手术缝合线 7间断地将连接件 2与正常食管断端 81缝合固定在一起。然后，将本发明之生物诱导型人体腔管代用品 4的近端***远端的正常食管断端 82，同样，要将远端，即靠近胃的正常食管断端 82，套在本发明之生物诱导型人体腔管代用品 4的远端上，将远端正常食管断端 82的黏膜置于本发明之生物诱导型人体腔管代用品 4的近端连接件 2之下，用手术缝合线 7间断地将本发明之生物诱导型人体腔管代用品 4的远端连接件 2与正常食管断端 82缝合固定在一起，即完成本发明之生物诱导型人体腔管代用品 4的植入固定。 Referring to Figures 26 and 27, a method of esophageal reconstruction using a bioinducible human lumen tube surrogate of the present invention is shown. After the esophagus of the lesion is removed, the proximal end, that is, the normal esophageal stump 81 near the entrance of the esophagus, is placed over the proximal end of the bioinducible human body tube substitute 4 of the present invention, and the mucosa of the normal esophageal end 81 is placed. Under the proximal connector 2 of the bioinducible human lumen tube substitute 4 of the present invention, the connector 2 is intermittently secured to the normal esophageal septum 81 by surgical sutures 7. Then, the proximal end of the biologically induced human lumen tube substitute 4 of the present invention is inserted into the distal normal esophageal end 82, and the distal end, that is, the normal esophageal end 82 adjacent to the stomach, is placed in the present invention. On the distal end of the bioinducible human lumen tube substitute 4, the mucosa of the distal normal esophageal end 82 is placed under the proximal connector 2 of the biologically induced human lumen tube substitute 4 of the present invention, and is surgically sutured. The line 7 intermittently sutures the distal connector 2 of the biologically-inducible human body tube substitute 4 of the present invention and the normal esophageal end 82, thereby completing the implantation of the biologically-inducible human body tube substitute 4 of the present invention. Fixed.

[125] 手术后，新生食管会依托本发明之生物诱导型人体腔管代用品 4的外壁爬行、生长、上皮化和疤痕组织生长稳定。特别是，当本发明之生物诱导型人体腔管代用品的可吸收涂层 3含有生长因子 32和种子细胞 33吋，更能有效促进新生食管的形成、上皮化和疤痕组织的稳定。 [125] After the operation, the neonatal esophagus will rely on the outer wall of the biologically induced human lumen tube substitute 4 of the present invention to crawl, grow, epithelialize, and scar tissue growth stably. In particular, when the absorbable coating 3 of the bioinducible human body tube substitute of the present invention contains growth factor 32 and seed cells, it is more effective in promoting the formation of neonatal esophagus, epithelialization, and stabilization of scar tissue.

[126] 本发明之生物诱导型人体腔管代用品在新生食管未形成前，是包裹在植入的本发明之生物诱导型人体腔管代用品外壁周围的纤维***形成的一条与两端吻合口正常食管组织相连续的密闭管道，起到人工食管的作用，保证食物顺利进入胃。在新生食管形成的早期，起到保护新生食管的作用，在新生食管生长过程中，起到促进新生食管生长、黏膜上皮化和稳定疤痕组织的作用，并抵抗新生食管的狭窄。在新生食管组织完全稳定后，可以在消化内镜的直视下，将本发明之生物诱导型人体腔管代用品出体外。新生食管的组织结构，实质上是一条通过纤维***修复为主，能再生出复层黏膜上皮、黏膜下肌层和腺体，肌层为瘢痕修复纤维***填充形成，没有收缩功能的瘢痕管道。 [126] The biologically-inducible human lumen tube substitute of the present invention is formed by one or both ends of fibrous connective tissue surrounding the outer wall of the implanted biologically induced human lumen tube substitute before the formation of the new esophagus. The anastomosis of the normal esophageal tissue is a closed tube that acts as an artificial esophagus to ensure that the food enters the stomach smoothly. In the early stage of neonatal esophageal formation, it protects the neonatal esophagus and promotes neonatal esophageal growth, mucosal epithelialization and stabilization of scar tissue during neonatal esophageal growth, and resists the narrowing of the neonatal esophagus. After the neonatal esophageal tissue is completely stabilized, the biologically inducible human body tube substitute of the present invention can be excreted under direct vision of the digestive endoscope. The structure of the newborn esophagus, in essence It is a scar-conduit that is mainly composed of fibrous connective tissue repair, which can regenerate the stratified mucosal epithelium, submucosal muscle layer and gland, and the muscular layer is filled with scar-repairing fibrous connective tissue and has no contractile function.

[127] 实施例 11 : 本发明之生物诱导型人体腔管代用品用于气管重建 [127] Example 11: Bioinducible human body tube substitute of the present invention for tracheal reconstruction

[128] 在图 28和图 29中，展示了一种用本发明之生物诱导型人体腔管代用品进行气管重建的方法。在气管切除后，将近端，即靠近口腔的正常气管断端 83，套在本发明之生物诱导型人体腔管代用品 4的近端上，将近端正常气管断端 83 的黏膜置于本发明之生物诱导型人体腔管代用品 4的近端连接件 2之下，用手术缝合线 7间断地将连接件 2与正常气管断端 83缝合固定在一起。然后，将本发明之生物诱导型人体腔管代用品 4的远端***远端的正常气管断端 84，将远端正常气管断端 84的黏膜置于本发明之生物诱导型人体腔管代用品 4的远端连接件 2之上，用手术缝合线 7间断地将本发明之生物诱导型人体腔管代用品 4 的远端连接件 2与正常气管断端 84缝合固定在一起，即完成本发明之生物诱导型人体腔管代用品 4的植入固定。 In Figures 28 and 29, a method of tracheal reconstruction using the bioinducible human lumen tube substitute of the present invention is shown. After the tracheotomy, the proximal end, that is, the normal tracheal stump 83 near the oral cavity, is placed over the proximal end of the bioinducible human lumen tube substitute 4 of the present invention, and the mucosa of the proximal normal tracheal stump 83 is placed. Under the proximal connector 2 of the bioinducible human lumen tube substitute 4 of the present invention, the connector 2 is intermittently secured to the normal tracheal stump 83 by surgical sutures 7. Then, the distal end of the biologically induced human lumen tube substitute 4 of the present invention is inserted into the distal normal tracheal end 84, and the mucosa of the distal normal tracheal end 84 is placed in the biologically induced human lumen of the present invention. On the distal connector 2 of the article 4, the distal end connector 2 of the biologically-inducible human body tube substitute 4 of the present invention is intermittently sutured and fixed with the surgical suture 7 to the normal tracheal end 84. The implant of the biologically induced human lumen tube substitute 4 of the present invention is fixed.

[129] 手术后，新生气管会依托本发明之生物诱导型人体腔管代用品 4的外壁爬行[129] After the operation, the new angry tube will crawl on the outer wall of the biologically induced human lumen tube substitute 4 of the present invention.

、生长、上皮化和疤痕组织生长稳定。 Growth, epithelialization, and scar tissue growth are stable.

[130] 本发明之生物诱导型人体腔管代用品 4在新生气管未形成前，起到人工气管的作用，保证呼吸通畅。在新生气管形成的早期，起到保护新生气管的作用，在新生气管生长过程中，起到促进新生气管生长、黏膜上皮化和稳定疤痕组织的作用，并抵抗新生气管的狭窄。在新生气管组织完全稳定后，可以在气管镜的直视下，将本发明之生物诱导型人体腔管代用品 4取出体外。 [130] The biologically induced human body tube substitute of the present invention 4 functions as an artificial air tube to ensure smooth breathing before the new gas tube is formed. In the early stage of the formation of the new gas tube, it plays a role in protecting the new gas tube. During the growth of the new gas tube, it plays a role in promoting the growth of new gas tubes, mucous epithelialization and stabilizing scar tissue, and resisting the narrowness of the new gas tube. After the new eschar tube tissue is completely stabilized, the biologically induced human lumen tube substitute 4 of the present invention can be taken out of the body under direct vision of the bronchoscope.

[131] 实施例 12 : 本发明之生物诱导型人体腔管代用品用于尿道重建 [131] Example 12: Bioinducible human body tube substitute of the present invention is used for urethral reconstruction

[132] 参考图 30和图 31，展示了一种用本发明之生物诱导型人体腔管代用品进行尿道重建的方法。在尿道损伤后，将近端，即靠近尿道口的正常尿道断端 83，套在本发明之生物诱导型人体腔管代用品 4的近端上，将近端正常尿道断端 83 的黏膜置于本发明之生物诱导型人体腔管代用品 4的近端连接件 2之下，用手术缝合线 7间断地将连接件 2与正常尿道断端 85缝合固定在一起。然后，将本发明之生物诱导型人体腔管代用品 4的远端***远端的正常尿道断端 86，将远端正常尿道断端 86的黏膜置于本发明之生物诱导型人体腔管代用品 4的远端连接件 2之上，用手术缝合线 7间断地将本发明之生物诱导型人体腔管代用品 4 的远端连接件 2与正常尿道断端 84缝合固定在一起，即完成本发明之生物诱导型人体腔管代用品 4的植入固定。 Referring to Figures 30 and 31, a method of urethral reconstruction using the bioinducible human lumen tube surrogate of the present invention is shown. After the urethral injury, the proximal end, that is, the normal urethral stump 83 close to the urethral opening, is placed on the proximal end of the bioinducible human lumen tube substitute 4 of the present invention, and the mucosa of the proximal normal urethral stump 83 is placed. Under the proximal connector 2 of the bioinducible human lumen tube substitute 4 of the present invention, the connector 2 is intermittently secured to the normal urethral stump 85 by surgical sutures 7. Then, the distal end of the biologically induced human lumen tube substitute 4 of the present invention is inserted into the distal normal urethral stump 86, and the mucosa of the distal normal urethral stump 86 is placed in the biologically induced human lumen of the present invention. Remote connection of supplies 4 Above the connector 2, the distal end connector 2 of the biologically-inducible human body tube substitute 4 of the present invention is sutured and fixed together with the normal urethral stump 84 by surgical suture 7, thereby completing the biological induction of the present invention. The implant of the human body tube substitute 4 is fixed.

[133] 手术后，新生尿道会依托本发明之生物诱导型人体腔管代用品 4的外壁爬行、生长、上皮化和疤痕组织生长稳定。 [133] After the operation, the newborn urethra will rely on the outer wall of the bioinducible human body tube substitute 4 of the present invention to be crawled, grown, epithelialized, and scar tissue stable.

[134] 本发明之生物诱导型人体腔管代用品 4在新生尿道未形成前，起到人工尿道的作用，保证呼吸通畅。在新生尿道形成的早期，起到保护新生尿道的作用，在新生尿道生长过程中，起到促进新生尿道生长、黏膜上皮化和稳定疤痕组织的作用，并抵抗新生尿道的狭窄。在新生尿道组织完全稳定后，可以在尿道镜的直视下，将本发明之生物诱导型人体腔管代用品 4取出体外。 [134] The biologically induced human lumen tube substitute of the present invention 4 functions as an artificial urethra before the formation of the new urethra to ensure smooth breathing. In the early stage of neonatal urethra formation, it protects the newborn urethra and promotes the growth of new urinary tract, mucosal epithelialization and stable scar tissue during the growth of the new urethra, and resists the narrowing of the new urethra. After the neonatal urethral tissue is completely stabilized, the biologically induced human lumen tube substitute 4 of the present invention can be taken out of the body under direct vision of the urethra.

[135] 应该注意，本文中公开和说明的结构可以用其它效果相同的结构代替，同吋本发明所介绍的实施例并非实现本发明的唯一结构。虽然本发明的优先实施已在本文中予以介绍和说明，但本领域内的技术人员都清楚地知道这些实施例不过是举例说明而已，本领域内的技术人员可以做出无数的变化、改进和代替，而不会脱离本发明，因此，应按照本发明所附的权利要求书的精神和范围来限定本发明的保护范围。 It should be noted that the structures disclosed and illustrated herein may be replaced with other structures having the same effect, and the embodiments described herein are not the only structures that implement the invention. Although the preferred embodiments of the present invention have been described and illustrated herein, it is apparent to those skilled in the art that these embodiments are merely illustrative and that numerous modifications and improvements can be made by those skilled in the art. Instead, the scope of the invention is to be defined in accordance with the spirit and scope of the appended claims.

Claims

权利要求书 Claim

[Claim 1] 1、一种生物诱导型人体腔管代用品，是能在人体中长期植入的薄壁管状物，其包括： [Claim 1] 1. A biologically induced human lumen tube substitute, which is a thin-walled tube that can be implanted in the human body for a long time, and includes:

A.支撑管（1) ，所述支撑管（1) 是有弹性的薄壁管状物，其包含： A. Support tube (1), the support tube (1) is a flexible thin-walled tube comprising:

支撑架（11) ，设置为弹性的薄壁网状支架； Support frame (11), set as an elastic thin-walled mesh bracket;

柔性材料膜（12) ，设置为使所述柔性材料膜（12) 全部或部分包覆支撑架（11) ，或者附着在支撑架（11) 的内壁上或外壁上 a flexible material film (12) disposed such that the flexible material film (12) is wholly or partially covered by the support frame (11) or attached to the inner wall or the outer wall of the support frame (11)

B.连接件（2) ，所述连接件（2) 固定于支撑管（1) 上，设置为通过连接件（2) 使支撑管（1) 固定于人体食管断端（8) ；B. The connecting member (2), the connecting member (2) is fixed on the supporting tube (1), and is arranged to fix the supporting tube (1) to the human esophagus broken end (8) through the connecting member (2);

C . 可吸收涂层（3) ，所述可吸收涂层（3) 釆用在人体中可降解吸收且能促进组织再生的材料制造，设置在支撑管（1) 的外壁上 C. Absorbable coating (3), the absorbable coating (3) is made of a material which is degradable in the human body and can promote tissue regeneration, and is disposed on the outer wall of the support tube (1)

[Claim 2] 2、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于[Claim 2] 2. The biologically induced human body tube substitute according to claim 1, characterized in that

，所述可吸收涂层（3) 至少包括以下方式：仅含有可在人体中使用的生物降解材料（31) ；含有可在人体中使用的生物降解材料 (31) 和生长因子（32) ；含有可在人体中使用的生物降解材料 (31) 和种子细胞（33) ；以及含有可在人体中使用的生物降解材料 (31) 、生长因子 (32) 和种子细胞 (33) 。 The absorbable coating (3) comprises at least the following means: only biodegradable material (31) which can be used in human body; biodegradable material (31) and growth factor (32) which can be used in human body; Contains biodegradable materials (31) and seed cells (33) that can be used in humans; and biodegradable materials (31), growth factors (32) and seed cells (33) that can be used in humans.

[Claim 3] 3、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于 [Claim 3] 3. The biologically induced human body tube substitute according to claim 1, characterized in that

：所述支撑架（11) 被柔性材料膜（12) 可运动地包覆在柔性材料膜（12) 之间，至少包括以下方式：用 2层或 2层以上的柔性材料膜（12) 来包覆支撑架（11) 吋，柔性材料膜（12) 之间的结合处在支撑架（11) 的网孔中间，或者结合在支撑架（11) 的不容易变形部分，而支撑架（11) 可在柔性材料膜（12) 之间形成的空间内运动，柔性材料膜（12) 不对支撑架（11) 的运动造成过分的约束。 : the support frame (11) is movably covered between the flexible material films (12) by the flexible material film (12), at least including the following manner: using two or more layers of flexible material film (12) Covering the support frame (11) 吋, the joint between the flexible material films (12) is in the middle of the mesh of the support frame (11), or is combined with the non-deformable portion of the support frame (11), and the support frame (11) The movement of the flexible material film (12) does not excessively constrain the movement of the support frame (11).

4、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于4. The biologically induced human lumen tube substitute according to claim 1, wherein

：所述柔性材料膜（12) 用可吸收手术缝合线（7) 缝合固定在支撑架（11) 的内壁上或外壁上；或者柔性材料膜（12) 用不可吸手术缝合线（7) 可以拆卸地缝合固定在支撑架（11) 的内壁上或外壁上。 : the flexible material film (12) is sutured to the inner wall or the outer wall of the support frame (11) by an absorbable surgical suture (7); or the non-absorbable surgical suture (7) may be a flexible material film (12) It is detachably fixed to the inner wall or the outer wall of the support frame (11).

5、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述支撑架（11) 至少选自以下的薄壁网状支架：医用弹性材料丝或纤维编织成的网状结构薄壁管体；医用弹性材料丝绕成的螺旋弹簧组成的网状结构薄壁管体；经过数控加工后形成的能弯曲的有弹性的医用弹性材料网状结构薄壁管体；以及经过激光雕刻后的能弯曲的有弹性的医用弹性材料网状结构薄壁管体；其中 5. The biologically induced human body tube substitute according to claim 1, wherein: the support frame (11) is at least selected from the following thin-walled mesh supports: a medical elastic material wire or a fiber-woven mesh. Thin-walled tubular body; a thin-walled tubular body composed of a coiled spring of medical elastic material; a bendable elastic medical elastic material mesh-shaped thin-walled tubular body formed by numerical control processing; a laser-engravable flexible medical elastic material mesh-like thin-walled tubular body;

，所述医用弹性材料，至少选自：镍钛形状记忆合金（Nitinol合金）、 β钛合金、医用不锈钢、医用锆合金，医用锆铌合金、医用钛锆铌合金、无镍钛基形状记忆合金、以及弹性高分子材料。The medical elastic material is at least selected from the group consisting of: nickel-titanium shape memory alloy (Nitinol alloy), β titanium alloy, medical stainless steel, medical zirconium alloy, medical zirconium-niobium alloy, medical titanium zirconium-niobium alloy, nickel-free titanium-based shape memory alloy And elastic polymer materials.

6、根据权利要求 2所述生物诱导型人体腔管代用品，其特征在于：所述生物降解材料（31) 至少选自：聚乳酸、聚羟基乙酸、聚羟基丁酯、聚酸酐、聚己内酯、聚偶磷氮、聚磷腈、聚氨基酸、假聚氨基酸、聚原酸酯、聚酯尿垸、聚三亚甲基碳酸酯、聚乙二醇、聚对二氧六环酮、壳聚糖、胶原、明胶、透明质酸、甲壳素、海藻酸盐、藻酸钙凝胶、脱细胞基质、生物玻璃，及其共聚物或混合物。 6. The bioinducible human body tube substitute according to claim 2, wherein: the biodegradable material (31) is at least selected from the group consisting of: polylactic acid, polyglycolic acid, polyhydroxybutyl ester, polyanhydride, polyhexyl Lactone, polyphosphazene, polyphosphazene, polyamino acid, pseudopolyamino acid, polyorthoester, polyester urethane, polytrimethylene carbonate, polyethylene glycol, polydioxanone, shell Glycans, collagen, gelatin, hyaluronic acid, chitin, alginate, calcium alginate gel, acellular matrix, bioglass, and copolymers or mixtures thereof.

7、根据权利要求 2所述生物诱导型人体腔管代用品，其特征在于：所述生长因子（32) 至少选自：血小板类生长因子（血小板来源生长因子， PDGF; 骨肉瘤来源生长因子 ODGF) 、表皮生长因子类（表皮生长因子， EGF、转化生长因子， TGF-α和 TGF-β) 、成纤维细胞生长因子（FGF、 a-FGF β-FGF) 、类胰岛素生长因子（IGF-I、 IGF-II) 、神经生长因子（NGF) 、白细胞介素类生长因子（IL-1、 IL-2、 IL-3等）、红细胞生长素（EPO) 、集落刺激因子（CSF) ，及其混合物。 7. The biologically induced human lumen tube substitute according to claim 2, wherein: said growth factor (32) is at least selected from the group consisting of: platelet-like growth factor (platelet-derived growth factor, PDGF; osteosarcoma-derived growth factor ODGF). , epidermal growth factor (epidermal growth factor, EGF, transforming growth factor, TGF-α and TGF-β), fibroblast growth factor (FGF, a-FGF β-FGF), insulin-like growth factor (IGF-I) , IGF-II), nerve growth factor (NGF), interleukin growth factor (IL-1, IL-2, IL-3, etc.), erythrocyte growth factor (EPO), colony Stimulating factor (CSF), and mixtures thereof.

8、根据权利要求 2所述生物诱导型人体腔管代用品，其特征在于：所述种子细胞（33) 至少选自：自体食管黏膜上皮细胞、自体骨髓间干细胞、同种异体骨髓间干细胞、胚胎干细胞，及其混合物。 8. The biologically induced human lumen tube substitute according to claim 2, wherein: said seed cells (33) are at least selected from the group consisting of: autologous esophageal mucosal epithelial cells, autologous bone marrow stem cells, allogeneic bone marrow stem cells, Embryonic stem cells, and mixtures thereof.

9、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于 9. The biologically induced human lumen tube substitute according to claim 1, wherein

：所述连接件（2) 是用医用柔性材料丝或纤维，通过编织或针织制造的环状结构，连接件（2) 釆用的医用柔性材料，至少选自：涤纶（聚对苯二甲酸乙二酯纤维）、聚乙烯、聚丙烯、聚氨酯、聚四氟乙烯。 : The connecting piece (2) is a ring-shaped structure made of woven or knitted fabric with medical flexible material or fiber, and the medical flexible material for connecting piece (2), at least selected from: polyester (polyterephthalate) Ethylene diester fiber), polyethylene, polypropylene, polyurethane, polytetrafluoroethylene.

10、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述柔性材料膜（12) 是能在人体中长期植入的医用柔性材料制造的薄膜，至少选自：医用硅胶、聚氨酯、聚四氟乙烯，各种纤维增强性医用柔性薄膜。 10. The bioinductive human body tube substitute according to claim 1, wherein: the flexible material film (12) is a film made of a medical flexible material that can be implanted in a human body for a long period of time, at least selected from the group consisting of: Silicone, polyurethane, polytetrafluoroethylene, various fiber-reinforced medical flexible films.

1 1、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述连接件（2) 有 2个，连接件（2) 的宽度约 3mm〜15mm，分别缝合固定于支撑管（1 ) 的 2个端部，距离端部约 5mm〜20mm 1 1. The biologically induced human body tube substitute according to claim 1, wherein: the connecting member (2) has two, and the connecting member (2) has a width of about 3 mm to 15 mm, and is respectively fixed and supported by the support. 2 ends of the tube (1), about 5mm~20mm from the end

12、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述支撑管（1 ) 上设置有柔性材料膜（12) ，在支撑管（1 ) 端部的柔性材料膜（12) 和支撑管（1 ) 中间部的柔性材料膜 ( 12 ) 是釆用不同的柔性材料制造的。 12. The biologically induced human body tube substitute according to claim 1, wherein: the support tube (1) is provided with a flexible material film (12), and a flexible material film at the end of the support tube (1) (12) The flexible material film (12) at the middle of the support tube (1) is made of a different flexible material.

13、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述支撑管（1 ) 上的近端设置有能将支撑管（1 ) 取出体外的回收线 (5) 。 13. The biologically induced human body tube substitute according to claim 1, wherein: the proximal end of the support tube (1) is provided with a recovery line (5) capable of taking the support tube (1) out of the body.

14、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于：所述支撑管（1 ) 上的设置有具有单向阀作用的防返流装置（6 [Claim 15] 15、根据权利要求 1所述生物诱导型人体腔管代用品，其特征在于14. The biologically induced human body tube substitute according to claim 1, wherein: said support tube (1) is provided with an anti-backflow device having a check valve function (6) [Claim 15] 15. The biologically induced human body tube substitute according to claim 1, characterized in that

：所述可吸收涂层（3) 的厚度在 0.^m〜5mm之间，较佳值在 10μ m〜lmm之间。 The thickness of the absorbable coating (3) is between 0.^m and 5 mm, preferably between 10 μm and 1 mm.