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WO2006066483A1 - Adhesion preventing biologic film for tendon ligament and its application - Google Patents

Adhesion preventing biologic film for tendon ligament and its application Download PDF

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Publication number
WO2006066483A1
WO2006066483A1 PCT/CN2005/002012 CN2005002012W WO2006066483A1 WO 2006066483 A1 WO2006066483 A1 WO 2006066483A1 CN 2005002012 W CN2005002012 W CN 2005002012W WO 2006066483 A1 WO2006066483 A1 WO 2006066483A1
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tendon
ligament
adhesion
biofilm
present
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PCT/CN2005/002012
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French (fr)
Chinese (zh)
Inventor
Haiying Yu
Ping Hsu Hu
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Haiying Yu
Ping Hsu Hu
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Publication of WO2006066483A1 publication Critical patent/WO2006066483A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • 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
    • A61L31/00Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04Macromolecular materials
    • A61L31/043Proteins; Polypeptides; Degradation products thereof
    • A61L31/044Collagen

Definitions

  • the invention relates to a biofilm of tendon and ligament anti-adhesion and application thereof, and belongs to the technical field of medical biomaterials.
  • the ligament adhesion problem is a worldwide technical problem that needs to be solved.
  • the adhesion of tendons and ligaments after the orthopedic surgery affects the normal activities of the joints. More than 90% of the tendon sheath tendon injuries require a second postoperative elective release surgery.
  • the clinical use of dexamethasone hormone and bio-protein glue and other materials for anti-adhesion, but the effect is not obvious, can not effectively prevent the formation of tendon and ligament adhesion.
  • the object of the present invention is to provide a tendon and ligament anti-adhesion biofilm which is a sponge-like medical collagen material, which has the characteristics of stable structure, good biocompatibility and degradable absorption. Can be used for tendon and ligament anti-adhesion applications.
  • the thickness of the film is 0. 05 ⁇ 1. 5 mm.
  • the thickness of the film is 0. 05 ⁇ 1. 5 mm.
  • the thickness of the biofilm is preferably 1 ⁇ 1. 5 mm.
  • biofilm of the present invention for the preparation of a biofilm for preventing tendon and ligament adhesion after orthopedic surgery.
  • the application of the tendon and ligament anti-adhesion biofilm is to prevent the anti-adhesive biofilm from being in contact with the sheath of the tendon and the distal end of the ligament after the suture treatment in the clean state, and wrapping the ring around the sheath. Cover the damaged tendons and ligaments adequately.
  • the preparation method of the tendon and ligament anti-adhesion biofilm according to the present invention is a technical content well known to those skilled in the art, which is based on bovine tendon, which is treated by acid treatment to dissolve collagen, alkali treatment to remove impurities and enzymatic treatment. Hydrolyzed to form small peptides, cross-linked with chondroitin sulfate, freeze-dried at -30 ° C ⁇ - 50 ° C, sterilized with ethylene oxide to produce protein purity above 95%, pores 80 to 200 microns, thickness 0. 05 ⁇ 1. 5 mm spongy type I collagen biofilm.
  • the biofilm of the invention can be used for tendon and ligament anti-adhesion.
  • the anti-adhesion biofilm is directly wrapped around the damaged tendon or ligament, and the biofilm area is covered. Size depends on the size of the damaged tendon or ligament.
  • the biofilm of the present invention effectively blocks the direct contact between the tendon and the ligament tissue, and the external tissue of the tendon causes a pseudomembrane due to the special structure of the biofilm, and at the same time prevents the scar of the external cell from growing into a stick.
  • the tendon and ligament anti-adhesion biofilm of the present invention and application are subjected to animal experiments, and the tendon and ligament anti-adhesion biofilm of the present invention is used for animals with tendon and ligament injury, and it is confirmed by experiments that the present invention provides
  • the type I collagen is a material for the tendon and ligament anti-adhesion biofilm. It is convenient to use and better for the dexamethasone hormone and bio-protein glue and other materials used in clinical practice. The anti-adhesion effect is remarkable, and the post-operative animal limbs are damaged. With less scar formation, there is no need for a second postoperative elective release procedure.
  • a 30 mm anti-adhesive biofilm is wrapped directly over the damaged tendon or ligament; the outer skin is then sutured and plastered.
  • a 30 mm anti-adhesive biofilm is wrapped directly over the damaged tendon or ligament; the outer skin is then sutured and plastered.
  • the tendon and ligament anti-adhesion biofilm of the present invention has high protein purity, stable molecular structure, specific pore structure and thickness, and good biocompatibility and controllability to human tissues.
  • the degradation and absorption property is applied to prevent tendon and ligament adhesion after orthopedic surgery, has remarkable effect, and is convenient to use, and has wide application value.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Materials For Medical Uses (AREA)

Abstract

The present invention discloses a adhesion preventing biologic film for tendon ligament and its application. The biological film is a sponge collagen protein, the protein purity is greater than 95%, the hole size is from 80 to 200um,and the thickness from 0.05mm to 1.5mm.Covering the tendon or ligament sufficiently after suturing by circularity swathing method under clean condition during operation, and proper early moving after operation, can cause peripheral tissues to form artificial films on the collagen films, and to prevent the adhesion between peripheral tissues and tendons, and therefore obtain the effect of preventing adhesion between tendons and ligaments. The present invention has the following advantages when applied on wounded tendon or ligament, such as the prevention of adhesion, the stabilization of structure, the proper biological compatibility, and the probability of degradation and absorption, ect, and therefore, the present invention can be applied broadly.

Description

肌腱、 韧带防粘连生物膜及其应用  Tendon, ligament anti-adhesion biofilm and its application
技术领域 Technical field
本发明涉及一种肌腱、 韧带防粘连的生物膜及其应用, 属于医学生物 材料技术领域。  The invention relates to a biofilm of tendon and ligament anti-adhesion and application thereof, and belongs to the technical field of medical biomaterials.
背景技术 Background technique
目前, 随着医疗科学技术的进步及医学材料的不断发展, 在医学生物 材料领域以胶原蛋白为基础的产品获得了显著的发展, 如中国专利, 专利 号为 021212779, 专利名称为医用胶原蛋白材料及其制造工艺公开了一种 医用胶原蛋白材料, 以牛肌腱组织为基料, 经过除杂、 清洗、 酸、 碱、 酶 处理、 硫酸软骨剂交联、 冷冻干燥及环氧乙烷灭菌等工序制成具有孔隙、 海绵状医用胶原蛋白材料, 目前, 在临床上用于硬脑膜、 硬脊膜的修复和 防粘连。 使用这种材料与技术扩大和延伸到其他治疗领域是医学生物材料 领域的重要课题。  At present, with the advancement of medical science and technology and the continuous development of medical materials, collagen-based products in the field of medical biomaterials have achieved remarkable development, such as Chinese patent, patent number 021212779, patent name is medical collagen material. And its manufacturing process discloses a medical collagen material based on bovine tendon tissue, which is subjected to impurity removal, washing, acid, alkali, enzyme treatment, cross-linking of chondroitin sulfate, freeze drying and ethylene oxide sterilization. The process is made of a porous, sponge-like medical collagen material, which is currently used clinically for the repair and anti-adhesion of the dura mater, dura mater. The use of this material and technology to expand and extend to other therapeutic areas is an important topic in the field of medical biomaterials.
目前, 解决恢复骨外科手部因肌腱与韧带损伤术后的肌腱, 韧带粘连 问题是世界性的急需解决的技术难题, 骨科手术后因瘢痕的形成造成肌腱 和韧带的粘连进而影响关节的正常活动, 90%以上的无腱鞘肌腱损伤都需 要进行第一次术后的二次择期松解手术。 目前, 临床使用的地塞米松激素 和生物蛋白胶以及其他材料的防粘连, 但效果不明显, 不能有效的防止肌 腱、 韧带粘连的形成。  At present, to solve the problem of tendon adhesion and ligament injury after restoring the orthopedic surgery, the ligament adhesion problem is a worldwide technical problem that needs to be solved. The adhesion of tendons and ligaments after the orthopedic surgery affects the normal activities of the joints. More than 90% of the tendon sheath tendon injuries require a second postoperative elective release surgery. At present, the clinical use of dexamethasone hormone and bio-protein glue and other materials for anti-adhesion, but the effect is not obvious, can not effectively prevent the formation of tendon and ligament adhesion.
发明的公开 Disclosure of invention
本发明的目的是提供一种肌腱、 韧带防粘连生物膜, 该生物膜为海绵 状医用胶原蛋白材料, 具有结构稳定、生物相容性好、可降解吸收的特性, 可用于肌腱、 韧带防粘连应用。 The object of the present invention is to provide a tendon and ligament anti-adhesion biofilm which is a sponge-like medical collagen material, which has the characteristics of stable structure, good biocompatibility and degradable absorption. Can be used for tendon and ligament anti-adhesion applications.
为实现上述目的, 本发明釆用如下技术方案 :  In order to achieve the above object, the present invention uses the following technical solutions:
一种肌腱、 韧带防粘连生物膜, 该生物膜为海绵状胶原蛋白生物膜, 蛋白纯度为 95%以上, 孔隙为 80〜200微米, 厚度为 0. 05〜1. 5毫米。  5毫米。 The thickness of the film is 0. 05~1. 5 mm. The thickness of the film is 0. 05~1. 5 mm.
生物膜的厚度优选为 1〜1. 5毫米。  5毫米。 The thickness of the biofilm is preferably 1~1. 5 mm.
一种本发明所述的生物膜在制备防止骨科手术后肌腱、 韧带粘连的生 物膜中的应用。  The use of a biofilm of the present invention for the preparation of a biofilm for preventing tendon and ligament adhesion after orthopedic surgery.
所述的肌腱、 韧带防粘连生物膜的应用是将防粘连生物膜在洁净的情 况下与手术中缝合处理后的肌腱、 韧带远近端保留的鞘膜相接触, 采用环 裹包绕法管状环绕充分覆盖在受损的肌腱、 韧带上。  The application of the tendon and ligament anti-adhesion biofilm is to prevent the anti-adhesive biofilm from being in contact with the sheath of the tendon and the distal end of the ligament after the suture treatment in the clean state, and wrapping the ring around the sheath. Cover the damaged tendons and ligaments adequately.
本发明所述的肌腱、 韧带防粘连生物膜的制备方法是本领域技术人员 公知的技术内容, 是以牛肌腱为基料, 经过酸处理溶解胶原蛋白、 碱处理 去除杂蛋白、酶处理使其水解形成小分子肽、硫酸软骨交联、经过 -30°C〜 - 50°C冷冻干燥、 环氧乙烷灭菌后制成蛋白纯度在 95%以上、 孔隙为 80〜 200微米、 厚度 0. 05〜1. 5毫米的海绵状 I型胶原蛋白生物膜。  The preparation method of the tendon and ligament anti-adhesion biofilm according to the present invention is a technical content well known to those skilled in the art, which is based on bovine tendon, which is treated by acid treatment to dissolve collagen, alkali treatment to remove impurities and enzymatic treatment. Hydrolyzed to form small peptides, cross-linked with chondroitin sulfate, freeze-dried at -30 ° C ~ - 50 ° C, sterilized with ethylene oxide to produce protein purity above 95%, pores 80 to 200 microns, thickness 0. 05~1. 5 mm spongy type I collagen biofilm.
本发明的生物膜可用于肌腱、 韧带防粘连。 在进行手部或其他部位的 受损肌腱与韧带手术时, 在将其缝合后, 将防粘连生物膜直接使用环裹包 绕法, 管状环绕覆盖在受损的肌腱或韧带上, 生物膜面积大小视受损肌腱 或韧带大小而定。 本发明所述的生物膜有效阻断了肌腱和韧带外界组织和 其直接接触, 肌腱外部组织因生物膜的特殊结构使其产生假膜, 同时阻止 外部细胞的长入的瘢痕而形成粘连。 具体实施方式 The biofilm of the invention can be used for tendon and ligament anti-adhesion. In the case of damaged tendon and ligament surgery in the hand or other parts, after suturing the suture, the anti-adhesion biofilm is directly wrapped around the damaged tendon or ligament, and the biofilm area is covered. Size depends on the size of the damaged tendon or ligament. The biofilm of the present invention effectively blocks the direct contact between the tendon and the ligament tissue, and the external tissue of the tendon causes a pseudomembrane due to the special structure of the biofilm, and at the same time prevents the scar of the external cell from growing into a stick. detailed description
将本发明的肌腱、 韧带防粘连生物膜和应用进行动物实验, 给肌腱、 韧带损伤的动物使用本发明所述的肌腱、 韧带防粘连生物膜, 经实验后观 察证明, 本发明所提供的以 I型胶原蛋白为材料的肌腱、 韧带防粘连的生 物膜比现临床使用的地塞米松激素和生物蛋白胶以及其他材料使用方便, 防粘连效果显著,使术后实验动物四肢受损部位活动正常,较少瘢痕形成, 不需再进行第一次术后的二次择期松解手术。  The tendon and ligament anti-adhesion biofilm of the present invention and application are subjected to animal experiments, and the tendon and ligament anti-adhesion biofilm of the present invention is used for animals with tendon and ligament injury, and it is confirmed by experiments that the present invention provides The type I collagen is a material for the tendon and ligament anti-adhesion biofilm. It is convenient to use and better for the dexamethasone hormone and bio-protein glue and other materials used in clinical practice. The anti-adhesion effect is remarkable, and the post-operative animal limbs are damaged. With less scar formation, there is no need for a second postoperative elective release procedure.
实施例 1  Example 1
( 1 ) 以牛肌腱为基料, 经过酸、 碱、 酶处理及硫酸软骨交联, 冷 冻干燥、灭菌后制成蛋白纯度在 95%以上、孔隙为 146微米、 厚度 0. 2毫米的海绵状 I型胶原蛋白防粘连生物膜备用; (1) A sponge having a protein purity of 95% or more, a pore size of 146 μm, and a thickness of 0.2 mm, which is obtained by the treatment of the bovine tendon as a base material, which is subjected to an acid, a base, an enzyme treatment, and a cross-linking of the sulfated cartilage. Type I collagen anti-adhesion biofilm spare;
(2 ) 在动物被损伤的四肢肌腱和韧带进行手术缝合后, 将 20 X (2) 20 X after the surgical suture of the injured limbs and ligaments of the animal
30mm 的防粘连生物膜直接管状环绕覆盖在受损的肌腱或韧 带上; 然后外皮缝合并打石膏。  A 30 mm anti-adhesive biofilm is wrapped directly over the damaged tendon or ligament; the outer skin is then sutured and plastered.
(3) 手术 3天后被动活动损伤的四肢, 四周拆除石膏, 继续被动 活动损伤的四肢。 12周将动物处死观察,四肢关节活动正常, 较少瘢痕形成, 防粘连生物膜起到了使肌腱和外周地鞘管得 以再生和间接阻断肌腱和韧带外周围组织与其直接接触的 作用, 肌腱和韧带外部组织因生物膜的特殊结构和功能使其 产生新生的组织, 而起到防粘连效果显著。  (3) After 3 days of surgery, the limbs were passively injured, and the plaster was removed around the body to continue the passive movement of the limbs. The animals were sacrificed for 12 weeks, the joints of the extremities were normal, and scar formation was less. The anti-adhesion biofilm played a role in regenerating the tendon and the peripheral sheath and indirectly blocking the direct contact between the tendon and the surrounding tissues of the ligament, tendon and The external structure of the ligament causes a new tissue due to the special structure and function of the biofilm, and the anti-adhesion effect is remarkable.
实施例 2  Example 2
( 1 ) 由牛肌腱为基料, 经过酸、 碱、 酶处理及硫酸软骨交联, 冷 冻干燥、 灭菌后制成蛋白纯度在 95%以上、 孔隙为 146 m 、 厚度 1. 4 mm的海绵状 I型胶原蛋白防粘连生物膜备用;(1) Based on bovine tendon, acid, alkali, enzyme treatment and cross-linking of chondroitin sulfate, cold After freeze-drying and sterilizing, a spongy type I collagen anti-adhesion biofilm with a protein purity of more than 95%, a pore volume of 146 m, and a thickness of 1.4 mm is prepared;
(2 ) 在动物被损伤的四肢肌腱和韧带进行手术缝合后, 将 20 X (2) 20 X after the surgical suture of the injured limbs and ligaments of the animal
30mm 的防粘连生物膜直接管状环绕覆盖在受损的肌腱或韧 带上; 然后外皮缝合并打石膏。  A 30 mm anti-adhesive biofilm is wrapped directly over the damaged tendon or ligament; the outer skin is then sutured and plastered.
( 3 ) 手术 3天后被动活动损伤的四肢, 四周拆除石膏, 继续被动 活动损伤的四肢。 12周将动物处死观察,四肢关节活动正常, 较少瘢痕形成, 防粘连生物膜起到了使肌腱和外周地鞘管得 以再生和间接阻断肌腱和韧带外周围组织与其直接接触的 作用, 肌腱和韧带外部组织因生物膜的特殊结构和功能使其 产生新生的组织, 而起到防粘连效果显著。  (3) The limbs that were passively injured after 3 days of surgery, the plaster was removed around the limbs, and the limbs of the passive injury were continued. The animals were sacrificed for 12 weeks, the joints of the extremities were normal, and scar formation was less. The anti-adhesion biofilm played a role in regenerating the tendon and the peripheral sheath and indirectly blocking the direct contact between the tendon and the surrounding tissues of the ligament, tendon and The external structure of the ligament causes a new tissue due to the special structure and function of the biofilm, and the anti-adhesion effect is remarkable.
工业上的应用 Industrial application
本发明的优点与效益: 本发明所述的肌腱、 韧带防粘连生物膜, 其蛋 白纯度高, 分子结构稳定, 有特定的孔隙结构和厚度与人体组织有很好的 生物相容性和可控制的降解吸收性, 应用于骨科手术后防止肌腱和韧带粘 连, 具有显著效果, 且使用方便, 具有广泛的应用价值。  Advantages and Benefits of the Invention: The tendon and ligament anti-adhesion biofilm of the present invention has high protein purity, stable molecular structure, specific pore structure and thickness, and good biocompatibility and controllability to human tissues. The degradation and absorption property is applied to prevent tendon and ligament adhesion after orthopedic surgery, has remarkable effect, and is convenient to use, and has wide application value.

Claims

权 利 要 求 书 、 一种肌腱、 韧带防粘连生物膜, 其特征在于: 该生物膜为海绵状胶原 蛋白生物膜,蛋白纯度为 95%以上,孔隙为 80〜200微米,厚度为 0. 05〜 1. 5毫米。 〜1. 05~ 1 The thickness of the film is 0. 05~ 1 . 5 mm.
、 根据权利要求 1所述的一种肌腱、 韧带防粘连生物膜, 其特征在于: 生物膜的厚度为 1〜1. 5毫米。 5毫米。 The thickness of the biofilm is 1~1. 5 mm.
、 一种权利要求 1所述的生物膜在制备防止骨科手术后肌腱、 韧带粘连 的生物膜中的应用。 The use of the biofilm of claim 1 for the preparation of a biofilm for preventing tendon and ligament adhesion after orthopedic surgery.
、 根据权利要求 3 所述的应用, 其特征在于: 将防粘连生物膜在洁净的 情况下与手术中缝合处理后的肌腱、 韧带远近端保留的鞘膜相接触, 采用环裹包绕法管状环绕充分覆盖在受损的肌腱或韧带上。 The application according to claim 3, wherein: the anti-adhesion biofilm is in contact with the sheath of the tendon and the distal end of the ligament after the suture treatment in the clean state, and the loop is wrapped around the tubular tube. Surround the full coverage of the damaged tendon or ligament.
PCT/CN2005/002012 2004-12-24 2005-11-25 Adhesion preventing biologic film for tendon ligament and its application WO2006066483A1 (en)

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CNB2004101015975A CN100366303C (en) 2004-12-24 2004-12-24 Preparation and application of anti blocking biomembrane for tendon and ligament
CN200410101597.5 2004-12-24

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CN103393482B (en) * 2013-08-14 2016-04-06 北京瑞健高科生物科技有限公司 A kind of mammary prostheses supporting device based on tissue matrix material and preparation method thereof
CN105524965A (en) * 2016-02-26 2016-04-27 福建华灿制药有限公司 Extraction method of bovine tendon collagen
CN107335101B (en) * 2017-08-07 2022-10-04 北京湃生生物科技有限公司 Composite collagen tissue regeneration membrane and preparation method thereof
CN110893250B (en) * 2019-10-11 2022-03-15 许和平 Scar/adhesion barrier film and preparation method and application thereof

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