CN107320775A - 脱脂灭菌深低温同种异体骨的制备方法和应用 - Google Patents

脱脂灭菌深低温同种异体骨的制备方法和应用 Download PDF

Info

Publication number
CN107320775A
CN107320775A CN201710519509.0A CN201710519509A CN107320775A CN 107320775 A CN107320775 A CN 107320775A CN 201710519509 A CN201710519509 A CN 201710519509A CN 107320775 A CN107320775 A CN 107320775A
Authority
CN
China
Prior art keywords
bone
degreasing
low temperature
deep
sterilization
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201710519509.0A
Other languages
English (en)
Inventor
张旗
林志雄
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hubei Joint Biological Material Co Ltd
Original Assignee
Hubei Joint Biological Material Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hubei Joint Biological Material Co Ltd filed Critical Hubei Joint Biological Material Co Ltd
Priority to CN201710519509.0A priority Critical patent/CN107320775A/zh
Publication of CN107320775A publication Critical patent/CN107320775A/zh
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3608—Bone, e.g. demineralised bone matrix [DBM], bone powder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A61L27/365—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/40—Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Molecular Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Vascular Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Materials For Medical Uses (AREA)

Abstract

本发明涉及植入性生物材料医疗器械，具体是涉及一种脱脂灭菌深低温同种异体骨的制备方法和应用。脱脂灭菌深低温同种异体骨的制备方法，其特征在于包括如下步骤：用人同种异体骨作为原材料，切割成骨段、骨块、骨颗粒，清洗除去骨髓，于20～40℃温度下脱脂，酒精浸泡、纯化水清洗，然后包装，将包装后的产物存放在‑40℃以下的环境至少12小时，然后放入保温容器中，周围放置冰块，将容器封装后20～25kGy剂量的钴－60辐照灭菌，即制成脱脂灭菌深低温同种异体骨，贮存在‑40℃以下的环境。本发明具有可用于骨缺损植骨修复的、生物相容性和力学强度好、免疫排斥反应小、安全性高、可与受区愈合并逐渐替代为受体自身骨组织的特点。

Description

脱脂灭菌深低温同种异体骨的制备方法和应用
技术领域
本发明涉及植入性生物材料医疗器械，具体是涉及一种脱脂灭菌深低温同种异体骨的制备方法和应用。
背景技术
肿瘤、骨折等疾病可导致骨缺损和结构破坏，现有技术中应用自体骨、金属、高分子材料和陶瓷修复骨缺损。自体骨取材量受限，材质常为松质骨，力学强度达不到要求，外形难与受区一致，取材时增加病人创伤和并发症。金属、高分子材料和陶瓷的生物相容性差，不能形成新骨或者成骨能力差，难与受区骨愈合，外形也常难与受区匹配。也有深低温同种异体骨修复骨缺损的，但这种深低温同种异体骨仅在切取后进行深低温保存，未经过清除骨髓、脱脂、酒精浸泡、纯化水清洗、低温环境下辐照灭菌加工，这样使同种异体骨的免疫排斥反应症状相对明显、成骨能力差、引起伤口感染和疾病传播的风险也增大。
发明内容
本发明目的是提供一种用于骨缺损植骨修复的、生物相容性和力学强度好、免疫排斥反应小、安全性高、可与受区愈合并逐渐替代为受体自身骨组织的脱脂灭菌深低温同种异体骨的制备方法和应用。
为实现上述目的，本发明采取的技术方案是：脱脂灭菌深低温同种异体骨的制备方法，其特征在于包括如下步骤：用人同种异体骨作为原材料(取材于人同种骨)，切割成不同大小的骨段、骨块、骨颗粒，清洗除去骨髓，于20～40℃温度下脱脂，酒精浸泡、纯化水清洗，然后包装，将包装后的产物存放在-40℃以下的环境至少12小时，然后放入保温容器中，周围放置冰块，将容器封装后20～25kGy剂量的钴－60辐照灭菌，即制成脱脂灭菌深低温同种异体骨，贮存在-40℃以下的环境。
所述脱脂为：于20～40℃温度下，采用三氯甲烷:甲醇溶液的体积比为1:1的混合溶液浸泡骨粉(骨段、骨块、骨颗粒清洗除去骨髓后的)并振动，持续时间为24小时，期间更换混合溶液。
所述酒精浸泡为乙醇与过氧乙酸的混合溶液(其中，乙醇的质量分数为24％，过氧乙酸的质量分数为1％)浸泡4小时并振动。
上述脱脂灭菌深低温同种异体骨的应用，其特征在于：临床使用时，将包装有脱脂灭菌深低温同种异体骨的包装打开，将脱脂灭菌深低温同种异体骨放入生理盐水中复温达到37℃，切割成适当大小，植入骨缺损部位，进行内固定后即完成脱脂灭菌深低温同种异体骨的植入。
所述深低温为-40℃以下的环境。
本发明的有益效果是：脱脂灭菌深低温同种异体骨取材于人同种骨，所以骨组织的微组织结构和物质成分更有利于新骨生长，对受区组织刺激性小，所以生物相容好，且有利于植入骨愈合和通过组织“爬行替代”生物学反应过程逐渐衍变成病人自身骨组织，不需要再次手术取出植入物；清除骨髓、脱脂和酒精浸泡能消化残存的细胞膜、完全去掉了细胞基质，以便植入骨能为宿主细胞所适应，并使免疫原性大为下降，免疫排斥基本消失(免疫排斥反应小、安全性高)，新骨形成能力增加，可与受区愈合并逐渐替代为受体自身骨组织可与受区愈合并逐渐替代为受体自身骨组织(不需要再次手术取出)。同时清除骨髓、脱脂和酒精浸泡能清除和灭活了病毒等病原体，为移植传播疾病的预防提供了另一道屏障。低温环境下辐照灭菌可灭活微生物使产品成为无菌产品，进一步提高产品的安全性，使产品在打开内包装塑料袋后即可直接植入，同时低温环境可使产品在辐照灭菌过程中防止蛋白活性成分的破坏。本发明产品不经过冷冻干燥脱水处理、而用深低温贮存，使本发明产品保持生物力学强度(力学强度好)。
本发明可用于肿瘤、骨折等疾病骨缺损的植骨修复。
具体实施方式
脱脂灭菌深低温同种异体骨的制备方法，包括如下步骤：用人同种异体骨作为原材料(取材于人同种骨)，切割成不同大小的骨段、骨块、骨颗粒，清洗除去骨髓，于20～40℃温度下脱脂，酒精浸泡、纯化水清洗，然后包装，将包装后的产物存放在-40℃以下的环境至少12小时，然后放入保温容器中，周围放置冰块，将容器封装后20～25kGy剂量的钴－60辐照灭菌，即制成脱脂灭菌深低温同种异体骨，贮存在-40℃以下的环境。
所述脱脂为：于20～40℃温度下，采用三氯甲烷:甲醇溶液的体积比为1:1的混合溶液浸泡骨粉(骨段、骨块、骨颗粒清洗除去骨髓后的)并振动，持续时间为24小时，期间更换混合溶液。
所述酒精浸泡为乙醇与过氧乙酸的混合溶液(其中，乙醇的质量分数为24％，过氧乙酸的质量分数为1％)。
上述脱脂灭菌深低温同种异体骨的应用，临床使用时，将包装有脱脂灭菌深低温同种异体骨的包装打开，将脱脂灭菌深低温同种异体骨放入生理盐水中复温达到37℃，切割成适当大小，植入骨缺损部位，进行内固定后即完成脱脂灭菌深低温同种异体骨的植入。

Claims (4)

1.脱脂灭菌深低温同种异体骨的制备方法，其特征在于包括如下步骤：用人同种异体骨作为原材料，切割成骨段、骨块、骨颗粒，清洗除去骨髓，于20～40℃温度下脱脂，酒精浸泡、纯化水清洗，然后包装，将包装后的产物存放在-40℃以下的环境至少12小时，然后放入保温容器中，周围放置冰块，将容器封装后20～25kGy剂量的钴－60辐照灭菌，即制成脱脂灭菌深低温同种异体骨，贮存在-40℃以下的环境。
2.根据权利要求1所述的脱脂灭菌深低温同种异体骨的制备方法，其特征在于所述脱脂为：于20～40℃温度下，采用三氯甲烷:甲醇溶液的体积比为1:1的混合溶液浸泡骨粉并振动，持续时间为24小时，期间更换混合溶液。
3.根据权利要求1所述的脱脂灭菌深低温同种异体骨的制备方法，其特征在于所述酒精浸泡溶液为乙醇与过氧乙酸的混合溶液浸泡4小时并振动。
4.如权利要求1所述的脱脂灭菌深低温同种异体骨的应用，其特征在于：临床使用时，将包装有脱脂灭菌深低温同种异体骨的包装打开，将脱脂灭菌深低温同种异体骨放入生理盐水中复温1小时，切割成适当大小，植入骨缺损部位，进行内固定后即完成脱脂灭菌深低温同种异体骨的植入。
CN201710519509.0A 2017-06-30 2017-06-30 脱脂灭菌深低温同种异体骨的制备方法和应用 Withdrawn CN107320775A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710519509.0A CN107320775A (zh) 2017-06-30 2017-06-30 脱脂灭菌深低温同种异体骨的制备方法和应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710519509.0A CN107320775A (zh) 2017-06-30 2017-06-30 脱脂灭菌深低温同种异体骨的制备方法和应用

Publications (1)

Publication Number Publication Date
CN107320775A true CN107320775A (zh) 2017-11-07

Family

ID=60198456

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710519509.0A Withdrawn CN107320775A (zh) 2017-06-30 2017-06-30 脱脂灭菌深低温同种异体骨的制备方法和应用

Country Status (1)

Country Link
CN (1) CN107320775A (zh)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107753159A (zh) * 2017-11-10 2018-03-06 湖北联结生物材料有限公司 多片复合新骨形成加强型同种异体骨颈椎融合器
CN110075356A (zh) * 2019-03-28 2019-08-02 中国辐射防护研究院 一种用于外科治疗骨缺损的可塑性填充材料及其制备方法
CN111569150A (zh) * 2019-02-19 2020-08-25 上海兰玛生物材料有限公司 具备骨诱导活性的同种骨修复材料及其制法及其用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101164626A (zh) * 2007-10-16 2008-04-23 张旗 脱脂灭菌深低温同种异体骨的制备方法及应用
CN103623464A (zh) * 2013-05-07 2014-03-12 胡晓予 一种自体颅骨回植技术的制备方法
CN105126170A (zh) * 2015-08-18 2015-12-09 深圳兰度生物材料有限公司 脱细胞真皮基质及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101164626A (zh) * 2007-10-16 2008-04-23 张旗 脱脂灭菌深低温同种异体骨的制备方法及应用
CN103623464A (zh) * 2013-05-07 2014-03-12 胡晓予 一种自体颅骨回植技术的制备方法
CN105126170A (zh) * 2015-08-18 2015-12-09 深圳兰度生物材料有限公司 脱细胞真皮基质及其制备方法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107753159A (zh) * 2017-11-10 2018-03-06 湖北联结生物材料有限公司 多片复合新骨形成加强型同种异体骨颈椎融合器
CN111569150A (zh) * 2019-02-19 2020-08-25 上海兰玛生物材料有限公司 具备骨诱导活性的同种骨修复材料及其制法及其用途
CN110075356A (zh) * 2019-03-28 2019-08-02 中国辐射防护研究院 一种用于外科治疗骨缺损的可塑性填充材料及其制备方法
CN110075356B (zh) * 2019-03-28 2021-08-17 中国辐射防护研究院 一种用于外科治疗骨缺损的可塑性填充材料及其制备方法

Similar Documents

Publication Publication Date Title
Mainil-Varlet et al. Long-term in vivo degradation and bone reaction to various polylactides: 1. One-year results
Tarchala et al. Biomaterial‐stabilized soft tissue healing for healing of critical‐sized bone defects: the Masquelet technique
EP1647288A2 (en) Method and apparatus for repairing bone
US20110218646A1 (en) Bone implant matrix and method of preparing the same
RU2609201C1 (ru) Способ получения остеопластического материала
Kretlow et al. Evaluation of soft tissue coverage over porous polymethylmethacrylate space maintainers within nonhealing alveolar bone defects
CN107320775A (zh) 脱脂灭菌深低温同种异体骨的制备方法和应用
CN101164626A (zh) 脱脂灭菌深低温同种异体骨的制备方法及应用
RU2511455C2 (ru) Способ восполнения костных дефектов
GB2431408A (en) Bone material and a process for the preparation of bone material
CN110075356B (zh) 一种用于外科治疗骨缺损的可塑性填充材料及其制备方法
WO2019168428A1 (ru) Способ очистки костного и кожного матриксов с использованием сверхкритического флюида
Roux et al. Madreporic coral for cranial base reconstruction 8 years experience
CN113577393B (zh) 一种骨修复材料及其制备方法和应用
RU2722266C1 (ru) Лиофилизированный биологический биодеградируемый минерализованный костнопластический материал и способ его изготовления
RU86455U1 (ru) Биоинженерная конструкция
RU2172104C1 (ru) Способ изготовления имплантатов из губчатой костной ткани
CN102824655A (zh) 一种生物人工骨及其制备方法
CA3154767A1 (en) Extracellular matrix devices and methods of manufacture
Giardino et al. A resorbable biomaterial shaped as a tubular chamber and containing stem cells: a pilot study on artificial bone regeneration
CN209548149U (zh) 加强成骨型同种异体骨前路椎间隙融合器
RU2746529C1 (ru) Способ изготовления костнопластического материала
CN109847103A (zh) 一种人造血管及其制备方法
KR102287890B1 (ko) 두개악안면부 재건용 임플란트의 제조방법 및 이를 이용해 제조된 임플란트
US20220323648A1 (en) Extracellular matrix devices and methods of manufacture

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication
WW01 Invention patent application withdrawn after publication

Application publication date: 20171107