WO2012031491A1 - Artificial vessel of polysaccharide, preparation and use thereof - Google Patents

Artificial vessel of polysaccharide, preparation and use thereof Download PDF

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Publication number
WO2012031491A1
WO2012031491A1 PCT/CN2011/074724 CN2011074724W WO2012031491A1 WO 2012031491 A1 WO2012031491 A1 WO 2012031491A1 CN 2011074724 W CN2011074724 W CN 2011074724W WO 2012031491 A1 WO2012031491 A1 WO 2012031491A1
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Prior art keywords
polysaccharide
chitosan
chitin
blood vessel
artificial blood
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PCT/CN2011/074724
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French (fr)
Chinese (zh)
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刘万顺
韩宝芹
潘学理
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德州海利安生物科技股份有限公司
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Publication of WO2012031491A1 publication Critical patent/WO2012031491A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels

Definitions

  • the present invention relates to a medical material, and more particularly to a polysaccharide artificial blood vessel and a preparation method and application thereof. Background technique
  • tissue engineering type artificial blood vessels which is a hot research topic, but has not been widely used clinically.
  • tissue-engineered artificial blood vessels there are two main types of tissue-engineered artificial blood vessels, one is artificial polymeric materials, such as polyglycolic acid (PGA), polylactic acid (PLA), polyglycolic acid (PLLA), etc.
  • PGA polyglycolic acid
  • PLA polylactic acid
  • PLLA polyglycolic acid
  • the common features of these materials are: Plasticity and absorbability, but also due to its gradual decomposition into small molecules such as lactic acid, glycolic acid, etc. in the body, also produces a chronic inflammatory response.
  • the other type is materials extracted from natural tissues, such as silk fibroin, collagen, chitosan, alginic acid, etc.
  • a non-vascular stent woven with chitosan fibers is disclosed, the stent having a length of 100 ⁇ 3 mm and a diameter of 18 ⁇ 2 mm, and illustrating the non-vascular
  • the stent is a woven mesh structure; in the Chinese invention patent No. 200910264238.4, a vascular stent woven with chitosan fiber is disclosed, the stent has a length of 28-32 mm and a diameter of 16-20 mm, and is illustrated.
  • the blood vessel stent is a woven mesh structure.
  • the above two invention patents because they are woven into a network structure, can make liquids such as blood pass through the mesh, and have no anti-side leakage effect, so they can only be used for stenosis prevention and treatment of vascular lumens, and cannot be used as a substitute for artificial blood vessels. .
  • a polysaccharide artificial blood vessel characterized by a dense artificial blood vessel made of a water-insoluble polysaccharide fiber made of a polysaccharide and a colloidal solution made of a polysaccharide; the polysaccharide is carboxymethyl cellulose, hydroxy Propyl cellulose, hydroxyethyl cellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, carboxymethyl chitin, hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxy Propyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl chitosan, hydroxyethyl shell 1 or 2 of glycan, carboxymethyl hydroxyeth
  • the method for preparing a polysaccharide artificial blood vessel is characterized in that a polysaccharide colloid solution is uniformly coated on an artificial blood vessel mold having a cross-sectional diameter of 1-10 mm and a length of 2-50 cm, and the water-insoluble polysaccharide fiber is closely wound. Or weaving or weaving on the artificial blood vessel mold to form a dense polysaccharide fiber layer, and then coating the polysaccharide colloid solution on the polysaccharide fiber layer, drying by natural drying/heating, cross-linking with a crosslinking agent, and then drying naturally.
  • the polysaccharide fiber and the polysaccharide film together form a dense tubular structure, which is removed from the mold, cut, packaged, and sterilized to obtain a polysaccharide artificial blood vessel.
  • the above-mentioned polysaccharide artificial blood vessel is implanted into a human body as a artificial blood vessel in a clinical operation, and replaces damaged or defective blood vessels, thereby improving the application of blood supply conditions.
  • the polysaccharide artificial blood vessel of the invention has better compactness, stretchability, bendability, mechanical strength and flexibility, and can be slowly degraded and absorbed by the body after being implanted in an animal or a human body, without immunity. It has good biocompatibility and can promote the growth of vascular endothelial cells. It can be implanted into the body during wound healing surgery. It can replace the damaged or defective blood vessels as artificial blood vessels and improve the blood supply.
  • the polymer polysaccharide can be biodegradable, has no toxic and side effects, and has good gel formation, film forming property and spinnability, and some polysaccharides such as chitosan and hyaluronic acid also have good biological functions. It has the functions of promoting wound healing, inhibiting scar hyperplasia, antibacterial, etc. All of these characteristics give high molecular weight polysaccharides excellent performance as biomedical materials.
  • the chitin polysaccharide fiber is evenly wound on the stainless steel rod-shaped artificial blood vessel mold to form a dense tubular structure, and then the chitin polysaccharide fiber tube is tubular.
  • the structure is coated with chitosan acetic acid hydrocolloid solution having a mass concentration of 2% (the same below) (the mass concentration of acetic acid in the hydrocolloid solution of acetic acid is 1%), and naturally dried into a dense chitosan polysaccharide.
  • Membrane carefully remove the above-mentioned dense tubular structure made of chitin polysaccharide fiber and chitosan polysaccharide film from stainless steel rod-shaped artificial blood vessel mold, cut, package, 60 Co sterilization, and obtain a cross-sectional inner diameter of 2 mm. Polysaccharide artificial blood vessels.
  • the carboxymethyl cellulose polysaccharide fiber is evenly wound on the stainless steel rod-shaped artificial blood vessel mold to form a dense tubular structure, and then in the carboxyl group.
  • the cellulose-polysaccharide fiber tubular structure is coated with a chitosan acetic acid hydrocolloid solution having a mass concentration of 2% (the same below) (the mass concentration of acetic acid in the acetic acid hydrocolloid solution is 1%), and is naturally dried.
  • Dense chitosan polysaccharide film carefully remove the above-mentioned dense tubular structure made of carboxymethyl cellulose polysaccharide fiber and chitosan polysaccharide film from stainless steel rod-shaped artificial blood vessel mold, cut, package, 60 Co A polysaccharide artificial blood vessel having a cross-sectional inner diameter of 4 mm was prepared.
  • a glass rod-shaped artificial blood vessel mold having a surface length of 20 cm and a diameter of 6 mm is prepared by mixing a chitosan polysaccharide fiber and a chitin polysaccharide fiber in a mass ratio of 3:7, and is formed by a stainless steel rod.
  • the artificial blood vessel mold is woven to form a dense tubular structure, and the above 2% hydrocolloid solution of carboxymethyl chitin is coated on the tube, and naturally dried into a dense carboxymethyl chitin polysaccharide film, carefully from the glass rod-shaped artificial blood vessel mold.
  • the above-mentioned dense tubular structure made of chitin polysaccharide fiber, chitosan polysaccharide fiber and carboxymethyl chitin polysaccharide film was removed, and the polysaccharide having a cross-sectional inner diameter of 6 mm was prepared by cutting, packaging and 60 Co sterilization. Blood vessels.
  • a stainless steel tubular artificial blood vessel mold having a surface length of 50 cm and a diameter of 8 mm was uniformly coated with a carboxymethyl chitin-hyaluronic acid having a mass concentration of 2% on the surface of the tubular artificial blood vessel mold.
  • the polysaccharide colloidal aqueous solution (the mass ratio of carboxymethyl chitin to hyaluronic acid is 9:1), and the alginate polysaccharide fiber is uniformly and densely wound around the above-mentioned polysaccharide colloidal solution coated with carboxymethyl chitin-hyaluronic acid.
  • the above 2% carboxymethyl chitin-hyaluronic acid polysaccharide colloid solution is coated on the alginate fiber, and naturally dried into a dense polysaccharide film, and the tubular structure is immersed in a 1% pentane.
  • the aqueous solution of the aldehyde cross-linking agent was cross-linked for 60 min, taken out and then immersed in a 2% aqueous solution of sodium borohydride for 2 h, and then taken out and placed in clean water for 12 hours. After being taken out, it was naturally dried, carefully from the stainless steel tubular artificial blood vessel.
  • the dense tubular structure was removed from the mold, and cut, packaged, and 60 Co sterilized to obtain a polysaccharide artificial blood vessel having a cross-sectional inner diameter of 8 mm.
  • the chitin polysaccharide fiber, the carboxymethyl cellulose polysaccharide fiber, the chitosan polysaccharide fiber, and the alginate polysaccharide fiber are all water-insoluble polysaccharide fibers; the chitin polysaccharide fiber, The carboxymethyl cellulose polysaccharide fiber, the chitosan polysaccharide fiber or the alginate polysaccharide fiber is changed to hydroxypropyl cellulose, hydroxyethyl cellulose, hyaluronic acid, heparin, chondroitin sulfate, carboxymethyl chitin, Hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxypropyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, carboxymethyl chitos
  • the polysaccharide artificial blood vessel is a dense artificial blood vessel made of a water-insoluble polysaccharide fiber made of a polysaccharide and a colloidal solution made of a polysaccharide;
  • Polysaccharides are carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, carboxymethyl chitin, hydroxypropyl chitin, hydroxy Ethyl chitin, carboxymethyl hydroxypropyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl Chitosan, hydroxyethyl chitosan, carboxymethyl
  • the polysaccharide colloid solution when preparing the polysaccharide artificial blood vessel, is uniformly coated on the artificial blood vessel mold having a cross-sectional diameter of 1-10 mm and a length of 2-50 cm.
  • the water-insoluble polysaccharide fiber is tightly entangled or woven or woven on the artificial blood vessel mold to form a dense polysaccharide fiber layer, and then the polysaccharide colloid solution is coated on the polysaccharide fiber layer, dried by natural drying/heating, or crosslinked.
  • the agent is cross-linked, and then dried by natural drying/heating to form a dense film layer.
  • the polysaccharide fiber and the polysaccharide film together form a dense tubular structure, which is removed from the mold, cut, packaged and sterilized to obtain a cross section.
  • Polysaccharide artificial blood vessel having an inner diameter of 1-10 mm and a length of 2-50 cm;
  • the crosslinking agent is glyoxal, malondialdehyde, glutaraldehyde, ethylene glycol diglycidyl ether, butanediol diglycidyl ether Or one or two of epichlorohydrin;
  • the aqueous solution of the crosslinking agent or the ethanol solution has a mass percentage of 0.05-10%.
  • the water-insoluble polysaccharide fiber forms a dense tubular structure on the artificial blood vessel mold in a tightly wound, tightly woven, and tightly woven manner; the water-insoluble polysaccharide fiber plays a skeleton supporting role and increases The stretchability, bendability, mechanical strength and flexibility of the artificial blood vessel; the polysaccharide colloid solution is dried into a dense film layer in the inner layer or the outer layer of the polysaccharide fiber layer, thereby increasing the compactness of the artificial blood vessel, Stretchability, bendability, mechanical strength and flexibility play a role in preventing side leakage.
  • test dog walked back to normal one week after femoral artery artificial blood vessel replacement; the animal's movement and performance were normal during the observation period of 3 months, 6 months and 9 months after surgery.
  • Color ultrasound observation of the graft site showed that the blood flow of the artificial blood vessel was smooth, the port was well-matched, and there was no obvious stenosis and clogging.
  • the polysaccharide artificial blood vessels prepared in the embodiments of the present invention can obtain similar results in the functional evaluation test of animal blood vessel replacement, and can replace the damaged or defective blood vessels and improve the application of blood supply conditions.
  • the polysaccharide artificial blood vessel of the invention has good compactness, stretchability, bendability, mechanical strength and flexibility, and can be slowly degraded and absorbed by the body after being implanted in the human body or in the human body, and has no immunogenicity. It has good biocompatibility and can promote the growth of vascular endothelial cells. It can be implanted into the human body during clinical wound repair surgery as a substitute for damaged blood vessels, as an artificial blood vessel instead of injury or deficiency.
  • the polysaccharide artificial blood vessel of the present invention is implanted into the human body as a artificial blood vessel in a clinical operation, and replaces the damaged or defective blood vessel, thereby improving the application of the blood supply condition.

Abstract

An artificial vessel of polysaccharide is composed of a layer of polysaccharide fiber and a film layer which is formed by coating polysaccharide solution on the layer of polysaccharide fiber. The polysaccharide is one or two compounds selected from the group consisting of carboxymethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, hydroxymethyl chitin, hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxypropyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl chitosan, hydroxyethyl chitosan, carboxymethyl hydroxyethyl chitosan, carboxymethyl hydroxypropyl chitosan, hydroxypropyl hydroethyl chitosan, sulfonated chitosan or succinyl chitosan. The artificial vessel of polysaccharide has good tightness, tensility, pliability, mechanical strength and flexibility.

Description

一种多糖人工血管及其制备方法和应用  Polysaccharide artificial blood vessel and preparation method and application thereof
技术领域Technical field
[0001] 本发明涉及一种医用材料,特别是涉及一种多糖人工血管及其制备方法和应用。 背景技术 [0001] The present invention relates to a medical material, and more particularly to a polysaccharide artificial blood vessel and a preparation method and application thereof. Background technique
[0002] 人工血管在治疗血管性疾病和中青年创伤修复中具有重要的作用。人工血管最早在 20 世纪 50 年代研制成功并用于临床,经历了从简单到复杂的发展经历,其性能得到不断改善,越来越接近理想人工血管的性能要求。涤纶、聚四氟乙烯、聚氨酯等材料已经在大口径 ( > 6mm ) 人工血管的制造上取得较满意的效果, 5 年通畅率可达 90 %以上,因此常用作大、中口径的动脉移植。但上述材料在制造小口径 ( ≤ 6mm ) 人工血管中存在较多的问题,如易引起血栓、慢性炎症反应、内膜增生、远期通畅率低等,因此在小口径人工血管中的应用并不理想。 [0002] Artificial blood vessels play an important role in the treatment of vascular diseases and the repair of young and middle-aged wounds. Artificial blood vessels were first developed in the 1950s and used in clinical practice. From simple to complex development, their performance has been continuously improved and is getting closer to the performance requirements of ideal artificial blood vessels. Polyester, PTFE, polyurethane and other materials have achieved satisfactory results in the manufacture of large-diameter (> 6mm) artificial blood vessels. The 5-year patency rate can reach more than 90%, so it is often used as a large and medium-diameter arterial graft. However, the above materials have many problems in the manufacture of small caliber (≤ 6mm) artificial blood vessels, such as easy to cause thrombosis, chronic inflammation, intimal hyperplasia, low long-term patency rate, etc., so the application in small-caliber artificial blood vessels not ideal.
[0003] 随着生物材料科学的不断发展,可降解的高分子材料作为组织工程型人工血管受到越来越多的关注,是目前研究热点,但并未大量临床使用。目前,作为组织工程型人工血管主要有两类,一类是人工聚合材料,如聚羟基乙酸 (PGA) 、聚乳酸 (PLA) 、聚乙醇酸 (PLLA) 等,这些材料的共同特点是:具有可塑性和可吸收性,但由于其在体内逐步分解为小分子如乳酸、羟基乙酸等,也产生慢性炎症反应。另一类是从天然组织中提取的材料,如蚕丝蛋白、胶原蛋白、壳聚糖、海藻酸等,这些天然材料在自然界中分布广泛,易于制取,可降解吸收,具有良好的生物相容性,有利于细胞的附着和生长,经过衍生化改性和特殊制造工艺,可以得到理想的小口径人工血管,其技术关键是降低炎症反应、提高抗凝血性、提高远期通畅率、加快内皮化进程。 [0003] With the continuous development of biomaterial science, degradable polymer materials have received more and more attention as tissue engineering type artificial blood vessels, which is a hot research topic, but has not been widely used clinically. At present, there are two main types of tissue-engineered artificial blood vessels, one is artificial polymeric materials, such as polyglycolic acid (PGA), polylactic acid (PLA), polyglycolic acid (PLLA), etc. The common features of these materials are: Plasticity and absorbability, but also due to its gradual decomposition into small molecules such as lactic acid, glycolic acid, etc. in the body, also produces a chronic inflammatory response. The other type is materials extracted from natural tissues, such as silk fibroin, collagen, chitosan, alginic acid, etc. These natural materials are widely distributed in nature, easy to prepare, degradable and absorbable, and have good biocompatibility. Sexuality is conducive to cell attachment and growth. After derivatization modification and special manufacturing process, ideal small-caliber artificial blood vessels can be obtained. The key technology is to reduce inflammation, improve anticoagulantness, improve long-term patency rate, and accelerate endothelium. Process.
[0004] 在申请号为 200910264239.9 的中国发明专利中,公开了一种用壳聚糖纤维编织的非血管支架,支架的长度为 100 ± 3mm ,直径为 18 ± 2mm ,并图示了该非 血管支架为编织的网状结构;在申请号为 200910264238.4 的中国发明专利中,公开了一种用壳聚糖纤维编织的血管支架,支架的长度为 28-32mm ,直径为 16-20mm ,并图示了该血管支架为编织的网状结构。上述两个发明专利,由于其编织成网状结构,能够使血液等液体通过网孔,没有防侧漏作用,因此只能用于血管的管腔术后防治狭窄,不能作为人工血管的替代品。 [0004] In Chinese Patent Application No. 200910264239.9, a non-vascular stent woven with chitosan fibers is disclosed, the stent having a length of 100 ± 3 mm and a diameter of 18 ± 2 mm, and illustrating the non-vascular The stent is a woven mesh structure; in the Chinese invention patent No. 200910264238.4, a vascular stent woven with chitosan fiber is disclosed, the stent has a length of 28-32 mm and a diameter of 16-20 mm, and is illustrated. The blood vessel stent is a woven mesh structure. The above two invention patents, because they are woven into a network structure, can make liquids such as blood pass through the mesh, and have no anti-side leakage effect, so they can only be used for stenosis prevention and treatment of vascular lumens, and cannot be used as a substitute for artificial blood vessels. .
发明内容 Summary of the invention
[0005] 本发明的目的是提供一种多糖人工血管及其制备方法和应用,以克服现有技术的上述缺点。 [0005] It is an object of the present invention to provide a polysaccharide artificial blood vessel and a method and application thereof for overcoming the above disadvantages of the prior art.
[0006] 一种多糖人工血管,其特征是由多糖制成的水不溶性多糖纤维和由多糖制成的胶体溶液共同制成的致密的人工血管;所述的多糖是羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、肝素、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖中的 1 种或 2 种。 [0006] A polysaccharide artificial blood vessel characterized by a dense artificial blood vessel made of a water-insoluble polysaccharide fiber made of a polysaccharide and a colloidal solution made of a polysaccharide; the polysaccharide is carboxymethyl cellulose, hydroxy Propyl cellulose, hydroxyethyl cellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, carboxymethyl chitin, hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxy Propyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl chitosan, hydroxyethyl shell 1 or 2 of glycan, carboxymethyl hydroxyethyl chitosan, carboxymethyl hydroxypropyl chitosan, hydroxypropyl hydroxyethyl chitosan, sulfonated chitosan or succinyl chitosan Kind.
[0007] 上述的多糖人工血管的制备方法,其特征是在横截面直径为 1-10mm 、长度为 2-50cm 的人工血管模具上,均匀涂布多糖胶体溶液,将水不溶性多糖纤维紧密地缠绕或编织或机织在人工血管模具上,形成致密的多糖纤维层,再在多糖纤维层上涂布多糖胶体溶液,经自然干燥 / 加热干燥,或用交联剂进行交联,再经自然干燥 / 加热干燥,形成致密的膜层,多糖纤维和多糖膜共同形成致密的管状结构,从模具上取下,经裁切、包装、灭菌,制得多糖人工血管。 [0007] The method for preparing a polysaccharide artificial blood vessel is characterized in that a polysaccharide colloid solution is uniformly coated on an artificial blood vessel mold having a cross-sectional diameter of 1-10 mm and a length of 2-50 cm, and the water-insoluble polysaccharide fiber is closely wound. Or weaving or weaving on the artificial blood vessel mold to form a dense polysaccharide fiber layer, and then coating the polysaccharide colloid solution on the polysaccharide fiber layer, drying by natural drying/heating, cross-linking with a crosslinking agent, and then drying naturally. / Heating and drying to form a dense film layer, the polysaccharide fiber and the polysaccharide film together form a dense tubular structure, which is removed from the mold, cut, packaged, and sterilized to obtain a polysaccharide artificial blood vessel.
[0008] 上述的多糖人工血管作为人工血管在临床手术中植入人体内,替代损伤或缺损的血管,改善供血状况的应用。 [0008] The above-mentioned polysaccharide artificial blood vessel is implanted into a human body as a artificial blood vessel in a clinical operation, and replaces damaged or defective blood vessels, thereby improving the application of blood supply conditions.
[0009] 本发明的多糖人工血管具有较好的致密性、可拉伸性、可弯曲性、机械强 度和柔顺性,在植入动物体内或人体内后,可被机体缓慢降解吸收,无免疫原性,具有较好的生物相容性,并可促进血管内皮细胞的生长,可以在创伤修复手术中植入机体内,作为人工血管替代损伤或缺损的血管,改善供血状况。 [0009] The polysaccharide artificial blood vessel of the invention has better compactness, stretchability, bendability, mechanical strength and flexibility, and can be slowly degraded and absorbed by the body after being implanted in an animal or a human body, without immunity. It has good biocompatibility and can promote the growth of vascular endothelial cells. It can be implanted into the body during wound healing surgery. It can replace the damaged or defective blood vessels as artificial blood vessels and improve the blood supply.
[0010] 高分子多糖可生物降解、无毒副作用,还具有良好的成胶性、成膜性、可纺性,部分多糖如壳聚糖、透明质酸等还具有很好的生物学功能,具有促进创面愈合、抑制瘢痕增生、抗菌等作用,所有这些特点都赋予高分子多糖作为生物医用材料的优良性能。 [0010] The polymer polysaccharide can be biodegradable, has no toxic and side effects, and has good gel formation, film forming property and spinnability, and some polysaccharides such as chitosan and hyaluronic acid also have good biological functions. It has the functions of promoting wound healing, inhibiting scar hyperplasia, antibacterial, etc. All of these characteristics give high molecular weight polysaccharides excellent performance as biomedical materials.
具体实施方式 detailed description
[0011] 实施例 1 [0011] Embodiment 1
[0012] 取长度为 30cm 、直径为 2mm 的表面光滑的不锈钢棒状人工血管模具,将甲壳素多糖纤维在上述不锈钢棒状人工血管模具上均匀地缠绕形成致密的管状结构,再在甲壳素多糖纤维管状结构上涂布质量百分浓度为 2 % ( 下同 ) 的壳聚糖的醋酸水胶体溶液 ( 醋酸水胶体溶液中醋酸的质量百分浓度为 1 % ) ,自然干燥成致密的壳聚糖多糖膜,小心从不锈钢棒状人工血管模具上取下上述由甲壳素多糖纤维和壳聚糖多糖膜制成的致密的管状结构,经裁切、包装、 60 Co 灭菌,制得横截面内径 2mm 的多糖人工血管。 [0012] Taking a stainless steel rod-shaped artificial blood vessel mold having a length of 30 cm and a diameter of 2 mm, the chitin polysaccharide fiber is evenly wound on the stainless steel rod-shaped artificial blood vessel mold to form a dense tubular structure, and then the chitin polysaccharide fiber tube is tubular. The structure is coated with chitosan acetic acid hydrocolloid solution having a mass concentration of 2% (the same below) (the mass concentration of acetic acid in the hydrocolloid solution of acetic acid is 1%), and naturally dried into a dense chitosan polysaccharide. Membrane, carefully remove the above-mentioned dense tubular structure made of chitin polysaccharide fiber and chitosan polysaccharide film from stainless steel rod-shaped artificial blood vessel mold, cut, package, 60 Co sterilization, and obtain a cross-sectional inner diameter of 2 mm. Polysaccharide artificial blood vessels.
[0013] 实施例 2 [0013] Example 2
[0014] 取长度为 30cm 、直径为 4mm 的表面光滑的不锈钢棒状人工血管模具,将羧甲基纤维素多糖纤维在上述不锈钢棒状人工血管模具上均匀地缠绕形成致密的管状结构,再在羧甲基纤维素多糖纤维管状结构上涂布质量百分浓度为 2 % ( 下同 ) 的壳聚糖的醋酸水胶体溶液 ( 醋酸水胶体溶液中醋酸的质量百分浓度为 1 % ) ,自然干燥成致密的壳聚糖多糖膜,小心从不锈钢棒状人工血管模具上取下上述由羧甲基纤维素多糖纤维和壳聚糖多糖膜制成的致密的管状结构,经裁切、包 装、 60 Co 灭菌,制得横截面内径 4mm 的多糖人工血管。 [0014] Taking a stainless steel rod-shaped artificial blood vessel mold having a length of 30 cm and a diameter of 4 mm, the carboxymethyl cellulose polysaccharide fiber is evenly wound on the stainless steel rod-shaped artificial blood vessel mold to form a dense tubular structure, and then in the carboxyl group. The cellulose-polysaccharide fiber tubular structure is coated with a chitosan acetic acid hydrocolloid solution having a mass concentration of 2% (the same below) (the mass concentration of acetic acid in the acetic acid hydrocolloid solution is 1%), and is naturally dried. Dense chitosan polysaccharide film, carefully remove the above-mentioned dense tubular structure made of carboxymethyl cellulose polysaccharide fiber and chitosan polysaccharide film from stainless steel rod-shaped artificial blood vessel mold, cut, package, 60 Co A polysaccharide artificial blood vessel having a cross-sectional inner diameter of 4 mm was prepared.
[0015] 实施例 3 [0015] Embodiment 3
[0016] 取长度为 20cm 、直径为 6mm 的表面光滑的玻璃棒状人工血管模具,将由壳聚糖多糖纤维与甲壳素多糖纤维按质量比为 3 ∶ 7 混合后纺制成的线,沿不锈钢棒状人工血管模具编织形成致密的管状结构,在管状上涂布上述 2 %的羧甲基甲壳素的水胶体溶液,自然干燥成致密的羧甲基甲壳素多糖膜,小心从玻璃棒状人工血管模具上取下上述由甲壳素多糖纤维、壳聚糖多糖纤维和羧甲基甲壳素多糖膜制成的致密管状结构,经裁切、包装、 60 Co 灭菌,制得横截面内径为 6mm 的多糖人工血管。 [0016] A glass rod-shaped artificial blood vessel mold having a surface length of 20 cm and a diameter of 6 mm is prepared by mixing a chitosan polysaccharide fiber and a chitin polysaccharide fiber in a mass ratio of 3:7, and is formed by a stainless steel rod. The artificial blood vessel mold is woven to form a dense tubular structure, and the above 2% hydrocolloid solution of carboxymethyl chitin is coated on the tube, and naturally dried into a dense carboxymethyl chitin polysaccharide film, carefully from the glass rod-shaped artificial blood vessel mold. The above-mentioned dense tubular structure made of chitin polysaccharide fiber, chitosan polysaccharide fiber and carboxymethyl chitin polysaccharide film was removed, and the polysaccharide having a cross-sectional inner diameter of 6 mm was prepared by cutting, packaging and 60 Co sterilization. Blood vessels.
[0017] 实施例 4 [0017] Embodiment 4
[0018] 取长度为 50cm 、直径为 8mm 的表面光滑的不锈钢管状人工血管模具,在管状人工血管模具模具的表面均匀地涂布质量百分浓度为 2 %的羧甲基甲壳素 - 透明质酸的多糖胶体水溶液 ( 羧甲基甲壳素与透明质酸的质量比为 9 ∶ 1) ,取海藻酸多糖纤维均匀致密地缠绕在上述涂有羧甲基甲壳素 - 透明质酸的多糖胶体溶液的不锈钢管状模具上,再在海藻酸多糖纤维上涂布上述 2 %的羧甲基甲壳素 - 透明质酸的多糖胶体溶液,自然干燥成致密的多糖膜,将管状结构浸入含有 1 %的戊二醛交联剂的水溶液中,交联 60min ,取出后再浸入含有 2 %的硼氢化钠水溶液中还原 2h ,再取出放入洁净的水中浸泡 12h ,取出后自然晾干,小心从不锈钢管状人工血管模具上取下上述致密的管状结构,经裁切、包装、 60 Co 灭菌,制得横截面内径为 8mm 的多糖人工血管。 [0018] A stainless steel tubular artificial blood vessel mold having a surface length of 50 cm and a diameter of 8 mm was uniformly coated with a carboxymethyl chitin-hyaluronic acid having a mass concentration of 2% on the surface of the tubular artificial blood vessel mold. The polysaccharide colloidal aqueous solution (the mass ratio of carboxymethyl chitin to hyaluronic acid is 9:1), and the alginate polysaccharide fiber is uniformly and densely wound around the above-mentioned polysaccharide colloidal solution coated with carboxymethyl chitin-hyaluronic acid. On the stainless steel tubular mold, the above 2% carboxymethyl chitin-hyaluronic acid polysaccharide colloid solution is coated on the alginate fiber, and naturally dried into a dense polysaccharide film, and the tubular structure is immersed in a 1% pentane. The aqueous solution of the aldehyde cross-linking agent was cross-linked for 60 min, taken out and then immersed in a 2% aqueous solution of sodium borohydride for 2 h, and then taken out and placed in clean water for 12 hours. After being taken out, it was naturally dried, carefully from the stainless steel tubular artificial blood vessel. The dense tubular structure was removed from the mold, and cut, packaged, and 60 Co sterilized to obtain a polysaccharide artificial blood vessel having a cross-sectional inner diameter of 8 mm.
[0019] 在上述实施例 1 至实施例 4 中,甲壳素多糖纤维、羧甲基纤维素多糖纤维、壳聚糖多糖纤维和海藻酸多糖纤维均为水不溶性多糖纤维;将甲壳素多糖纤维、羧甲基纤维素多糖纤维、壳聚糖多糖纤维或海藻酸多糖纤维改为多糖是羟丙基 纤维素、羟乙基纤维素、透明质酸、肝素、硫酸软骨素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖的水不溶性纤维,均能达到同样的效果。 [0019] In the above Examples 1 to 4, the chitin polysaccharide fiber, the carboxymethyl cellulose polysaccharide fiber, the chitosan polysaccharide fiber, and the alginate polysaccharide fiber are all water-insoluble polysaccharide fibers; the chitin polysaccharide fiber, The carboxymethyl cellulose polysaccharide fiber, the chitosan polysaccharide fiber or the alginate polysaccharide fiber is changed to hydroxypropyl cellulose, hydroxyethyl cellulose, hyaluronic acid, heparin, chondroitin sulfate, carboxymethyl chitin, Hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxypropyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, carboxymethyl chitosan , Hydroxypropyl chitosan, hydroxyethyl chitosan, carboxymethyl hydroxyethyl chitosan, carboxymethyl hydroxypropyl chitosan, hydroxypropyl hydroxyethyl chitosan, sulfonated chitosan Or the water-insoluble fiber of succinyl chitosan can achieve the same effect.
[0020] 在上述实施例 1 至实施例 4 中,所述的多糖人工血管是由多糖制成的水不溶性多糖纤维和由多糖制成的胶体溶液共同制成的致密的人工血管;所述的多糖是羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、肝素、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖中的 1 种或 2 种;所述的多糖胶体溶液的质量百分浓度为 0.5-20 %。 [0020] In the above-mentioned Embodiments 1 to 4, the polysaccharide artificial blood vessel is a dense artificial blood vessel made of a water-insoluble polysaccharide fiber made of a polysaccharide and a colloidal solution made of a polysaccharide; Polysaccharides are carboxymethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, carboxymethyl chitin, hydroxypropyl chitin, hydroxy Ethyl chitin, carboxymethyl hydroxypropyl chitin, carboxymethyl hydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl Chitosan, hydroxyethyl chitosan, carboxymethyl hydroxyethyl chitosan, carboxymethyl hydroxypropyl chitosan, hydroxypropyl hydroxyethyl chitosan, sulfonated chitosan or succinyl One or two kinds of chitosan; the polysaccharide colloidal solution has a mass percentage of 0.5-20%.
[0021] 在上述实施例 1 至实施例 4 中,制备所述的多糖人工血管时,先在横截面直径为 1-10mm 、长度为 2-50cm 的人工血管模具上,均匀涂布多糖胶体溶液,将水不溶性多糖纤维紧密地缠绕或编织或机织在人工血管模具上,形成致密的多糖纤维层,再在多糖纤维层上涂布多糖胶体溶液,经自然干燥 / 加热干燥,或用交联剂进行交联,再经自然干燥 / 加热干燥,形成致密的膜层,多糖纤维和多糖膜共同形成致密的管状结构,从模具上取下,经裁切、包装、灭菌,制得横截面内径为 1-10mm 、长度为 2-50cm 的多糖人工血管;所述的交联剂是乙二醛、丙二醛、戊二醛、乙二醇双缩水甘油醚、丁二醇双缩水甘油醚或环氧氯丙烷中的 1 种或 2 种;交联剂的水溶液或乙醇溶液的质量百分浓度为 0.05-10 %。 [0021] In the above-mentioned Embodiments 1 to 4, when preparing the polysaccharide artificial blood vessel, the polysaccharide colloid solution is uniformly coated on the artificial blood vessel mold having a cross-sectional diameter of 1-10 mm and a length of 2-50 cm. The water-insoluble polysaccharide fiber is tightly entangled or woven or woven on the artificial blood vessel mold to form a dense polysaccharide fiber layer, and then the polysaccharide colloid solution is coated on the polysaccharide fiber layer, dried by natural drying/heating, or crosslinked. The agent is cross-linked, and then dried by natural drying/heating to form a dense film layer. The polysaccharide fiber and the polysaccharide film together form a dense tubular structure, which is removed from the mold, cut, packaged and sterilized to obtain a cross section. Polysaccharide artificial blood vessel having an inner diameter of 1-10 mm and a length of 2-50 cm; the crosslinking agent is glyoxal, malondialdehyde, glutaraldehyde, ethylene glycol diglycidyl ether, butanediol diglycidyl ether Or one or two of epichlorohydrin; the aqueous solution of the crosslinking agent or the ethanol solution has a mass percentage of 0.05-10%.
[0022] 在本发明的多糖人工血管中,水不溶性多糖纤维以紧密缠绕、紧密编织、 紧密机织的方式在人工血管模具上形成致密的管状结构;水不溶性多糖纤维起到了骨架支持作用,增加了人工血管的可拉伸性、可弯曲性、机械强度和柔顺性;所述的多糖胶体溶液在多糖纤维层的内层或外层干燥成致密的膜层,增加了人工血管的致密性、可拉伸性、可弯曲性、机械强度和柔顺性,起到了防止侧漏的作用。 [0022] In the polysaccharide artificial blood vessel of the present invention, the water-insoluble polysaccharide fiber forms a dense tubular structure on the artificial blood vessel mold in a tightly wound, tightly woven, and tightly woven manner; the water-insoluble polysaccharide fiber plays a skeleton supporting role and increases The stretchability, bendability, mechanical strength and flexibility of the artificial blood vessel; the polysaccharide colloid solution is dried into a dense film layer in the inner layer or the outer layer of the polysaccharide fiber layer, thereby increasing the compactness of the artificial blood vessel, Stretchability, bendability, mechanical strength and flexibility play a role in preventing side leakage.
[0023] 实施例 5 [0023] Example 5
[0024] 多糖人工血管的功能评价试验:取上述实施例 1 制得的横截面内径 2mm 的多糖人工血管,无菌条件下用手术剪剪取长度 4cm 的人工血管,以杂种犬为试验动物,采用戊巴比妥钠腹腔注射麻醉,剂量为 45mg/Kg 。手术切开试验犬大腿根内侧,手术暴露股动脉,用止血夹夹住一段长度为 8cm 的股动脉两端,截断股动脉 4cm ,采用端端缝合,将剪取的人工血管缝合到截断的股动脉处,取下止血夹,逐层缝合肌肉、皮肤。试验狗术后正常饲养,定期观察试验狗的行为状态,并进行超声检查股动脉血流情况。实验结果表明,股动脉人工血管置换术后 1 周,试验狗行走基本恢复正常;在术后 3 个月、 6 个月和 9 个月的观察期内,动物行动及表现均正常,对人工血管移植部位进行的彩色超声观察显示,人工血管血流通畅,端口吻合良好,无明显的狭窄和堵塞现象。 [0024] Functional evaluation test of polysaccharide artificial blood vessel: The polysaccharide artificial blood vessel having a cross-sectional inner diameter of 2 mm prepared in the above Example 1 was taken, and an artificial blood vessel of 4 cm in length was surgically cut under a sterile condition, and the hybrid dog was used as a test animal. Anesthesia was intraperitoneally injected with sodium pentobarbital at a dose of 45 mg/kg. Surgical incision of the inner thigh of the test dog, surgical exposure of the femoral artery, with a hemostatic clip to clamp a length of 8cm of the femoral artery, cut off the femoral artery 4cm, sutured with the end of the suture, the sutured artificial blood vessels sutured to the truncated strand At the artery, remove the hemostatic clip and suture the muscles and skin layer by layer. The test dogs were reared normally, and the behavioral state of the test dogs was observed regularly, and the blood flow of the femoral artery was examined by ultrasonography. The experimental results showed that the test dog walked back to normal one week after femoral artery artificial blood vessel replacement; the animal's movement and performance were normal during the observation period of 3 months, 6 months and 9 months after surgery. Color ultrasound observation of the graft site showed that the blood flow of the artificial blood vessel was smooth, the port was well-matched, and there was no obvious stenosis and clogging.
[0025] 本发明实施例中所制备的多糖人工血管,在动物血管替换的功能性评价试验研究中均能获得类似的结果,均能替代损伤或缺损的血管,改善供血状况的应用。 [0025] The polysaccharide artificial blood vessels prepared in the embodiments of the present invention can obtain similar results in the functional evaluation test of animal blood vessel replacement, and can replace the damaged or defective blood vessels and improve the application of blood supply conditions.
[0026][0026]
本发明的多糖人工血管具有较好的致密性、可拉伸性、可弯曲性、机械强度和柔顺性,在植入动物体内或人体内后,可被机体缓慢降解吸收,无免疫原性,具有较好的生物相容性,并可促进血管内皮细胞的生长,可以在临床创伤修复手术中植入人体内,作为损伤血管的替代物,作为人工血管替代损伤或缺 The polysaccharide artificial blood vessel of the invention has good compactness, stretchability, bendability, mechanical strength and flexibility, and can be slowly degraded and absorbed by the body after being implanted in the human body or in the human body, and has no immunogenicity. It has good biocompatibility and can promote the growth of vascular endothelial cells. It can be implanted into the human body during clinical wound repair surgery as a substitute for damaged blood vessels, as an artificial blood vessel instead of injury or deficiency.
损的血管,改善供血状况。因此,本发明的多糖人工血管作为人工血管在临床手术中植入人体内,替代损伤或缺损的血管,改善供血状况的应用。 Damaged blood vessels, improve blood supply. Therefore, the polysaccharide artificial blood vessel of the present invention is implanted into the human body as a artificial blood vessel in a clinical operation, and replaces the damaged or defective blood vessel, thereby improving the application of the blood supply condition.

Claims (1)

1. 一种多糖人工血管,其特征是由多糖制成的水不溶性多糖纤维和由多糖制成的胶体溶液共同制成的致密的人工血管;所述的多糖是羧甲基纤维素、羟丙基纤维素、羟乙基纤维素、透明质酸、海藻酸盐、肝素、硫酸软骨素、甲壳素、羧甲基甲壳素、羟丙基甲壳素、羟乙基甲壳素、羧甲基羟丙基甲壳素、羧甲基羟乙基甲壳素、羟丙基羟乙基甲壳素、磺酸化甲壳素、壳聚糖、羧甲基壳聚糖、羟丙基壳聚糖、羟乙基壳聚糖、羧甲基羟乙基壳聚糖、羧甲基羟丙基壳聚糖、羟丙基羟乙基壳聚糖、磺酸化壳聚糖或琥珀酰壳聚糖中的 1 种或 2 种。 A graft polysaccharide, characterized in that the dense artificial blood vessel made of a water-insoluble polysaccharides and polysaccharide fibers made of a colloidal solution of polysaccharides made common; the polysaccharide is carboxymethyl cellulose, hydroxypropyl Cellulose, hydroxyethyl cellulose, hyaluronic acid, alginate, heparin, chondroitin sulfate, chitin, carboxymethyl chitin, hydroxypropyl chitin, hydroxyethyl chitin, carboxymethyl hydroxypropyl Chitin, carboxymethylhydroxyethyl chitin, hydroxypropyl hydroxyethyl chitin, sulfonated chitin, chitosan, carboxymethyl chitosan, hydroxypropyl chitosan, hydroxyethyl shell 1 or 2 of sugar, carboxymethyl hydroxyethyl chitosan, carboxymethyl hydroxypropyl chitosan, hydroxypropyl hydroxyethyl chitosan, sulfonated chitosan or succinyl chitosan .
2. 如权利要求 1 所述的多糖人工血管,其特征是所述的多糖胶体溶液的质量百分浓度为 0.5-20 %。 The polysaccharide artificial blood vessel according to claim 1, wherein the polysaccharide colloidal solution has a mass percentage concentration of 0.5-20%.
3. 如权利要求 1 所述的多糖人工血管,其特征是所述的多糖人工血管的横截面内径为 1-10mm 、长度为 2-50cm 。Polysaccharides artificial blood vessel according to claim 1, characterized in that the cross-sectional diameter of the artificial blood vessel polysaccharide is 1-10mm, length 2-50cm.
4. 权利要求 1 所述的多糖人工血管的制备方法,其特征是在横截面直径为 1-10mm 、长度为 2-50cm 的人工血管模具上,均匀涂布多糖胶体溶液,将水不溶性多糖纤维紧密地缠绕或编织或机织在人工血管模具上,形成致密的多糖纤维层,再在多糖纤维层上涂布多糖胶体溶液,经自然干燥 / 加热干燥,或用交联剂进行交联,再经自然干燥 / 加热干燥,形成致密的膜层,多糖纤维和多糖膜共同形成致密的管状结构,从模具上取下,经裁切、包装、灭菌,制得多糖人工血管。 The method for preparing a polysaccharide artificial blood vessel according to claim 1, characterized in that the polysaccharide colloid solution is uniformly coated on the artificial blood vessel mold having a cross-sectional diameter of 1-10 mm and a length of 2-50 cm, and the water-insoluble polysaccharide fiber is used. Tightly entangled or woven or woven on the artificial blood vessel mold to form a dense polysaccharide fiber layer, and then coated with a polysaccharide colloid solution on the polysaccharide fiber layer, dried by natural drying/heating, or crosslinked with a crosslinking agent, and then After drying by natural drying/heating, a dense film layer is formed, and the polysaccharide fiber and the polysaccharide film together form a dense tubular structure, which is taken out from the mold, cut, packaged and sterilized to obtain a polysaccharide artificial blood vessel.
5. 如权利要求 4 所述的多糖人工血管的制备方法,其特征是所述的交联剂是乙二醛、丙二醛、戊二醛、乙二醇双缩水甘油醚、丁二醇双缩水甘油醚或环氧氯丙烷中的 1 种或 2 种;交联剂的水溶液或乙醇溶液的质量百分浓度为 0.05-10 %。 The method for preparing a polysaccharide artificial blood vessel according to claim 4, wherein the crosslinking agent is glyoxal, malondialdehyde, glutaraldehyde, ethylene glycol diglycidyl ether, butylene glycol double One or two of glycidyl ether or epichlorohydrin; the aqueous solution of the crosslinking agent or the ethanol solution has a mass percentage of 0.05-10%.
6. 权利要求 1 所述的多糖人工血管作为人工血管在临床手术中植入人体内,替代损伤或缺损的血管,改善供血状况的应用。 6. The use of the polysaccharide artificial blood vessel according to claim 1 as an artificial blood vessel in a human body during a clinical operation to replace a damaged or defective blood vessel and to improve a blood supply condition.
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