CN107812240B - 纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 - Google Patents
纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 Download PDFInfo
- Publication number
- CN107812240B CN107812240B CN201710976341.6A CN201710976341A CN107812240B CN 107812240 B CN107812240 B CN 107812240B CN 201710976341 A CN201710976341 A CN 201710976341A CN 107812240 B CN107812240 B CN 107812240B
- Authority
- CN
- China
- Prior art keywords
- zinc oxide
- gelatin
- nano zinc
- alpha
- bone cement
- 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.)
- Active
Links
- XLOMVQKBTHCTTD-UHFFFAOYSA-N zinc oxide Inorganic materials [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 title claims abstract description 70
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims abstract description 45
- 239000002639 bone cement Substances 0.000 title claims abstract description 40
- 239000011787 zinc oxide Substances 0.000 title claims abstract description 37
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 31
- 239000001506 calcium phosphate Substances 0.000 title claims abstract description 19
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims abstract description 19
- 235000011010 calcium phosphates Nutrition 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000000843 powder Substances 0.000 claims abstract description 52
- 108010010803 Gelatin Proteins 0.000 claims abstract description 34
- 239000008273 gelatin Substances 0.000 claims abstract description 34
- 229920000159 gelatin Polymers 0.000 claims abstract description 34
- 235000019322 gelatine Nutrition 0.000 claims abstract description 34
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 34
- 238000002156 mixing Methods 0.000 claims abstract description 21
- 238000003756 stirring Methods 0.000 claims abstract description 15
- 239000004568 cement Substances 0.000 claims abstract description 12
- 239000000463 material Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 11
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 10
- 239000007864 aqueous solution Substances 0.000 claims abstract description 10
- 238000004108 freeze drying Methods 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 238000002347 injection Methods 0.000 claims abstract description 8
- 239000007924 injection Substances 0.000 claims abstract description 8
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000007787 solid Substances 0.000 claims abstract description 7
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 5
- 238000003746 solid phase reaction Methods 0.000 claims abstract description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract 2
- 229910052791 calcium Inorganic materials 0.000 claims abstract 2
- 239000011575 calcium Substances 0.000 claims abstract 2
- 238000000498 ball milling Methods 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 4
- 238000003760 magnetic stirring Methods 0.000 claims description 4
- 238000010907 mechanical stirring Methods 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 238000001354 calcination Methods 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 4
- 210000000988 bone and bone Anatomy 0.000 abstract description 3
- 238000002324 minimally invasive surgery Methods 0.000 abstract description 3
- 239000011573 trace mineral Substances 0.000 abstract description 3
- 235000013619 trace mineral Nutrition 0.000 abstract description 3
- 208000035143 Bacterial infection Diseases 0.000 abstract description 2
- 208000022362 bacterial infectious disease Diseases 0.000 abstract description 2
- 230000008439 repair process Effects 0.000 abstract description 2
- -1 gelatin modified alpha-TCP Chemical class 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 229910021642 ultra pure water Inorganic materials 0.000 description 5
- 239000012498 ultrapure water Substances 0.000 description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 description 3
- 239000003607 modifier Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000000399 orthopedic effect Effects 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000003837 high-temperature calcination Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- 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
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- 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
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/222—Gelatin
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/06—Flowable or injectable implant compositions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dermatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Dental Preparations (AREA)
Abstract
本发明涉及一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥制备方法及其产品和应用,采用固相反应法将原料磷酸氢钙与碳酸钙混合后,煅烧球磨,制备α‑TCP粉末;将α‑TCP粉末加入明胶水溶液,高速搅拌后进行冷冻干燥,制备得到注射性能良好的明胶改性的α‑TCP粉末;将纳米氧化锌与明胶改性的α‑TCP粉末充分混合,与固化液按液固比0.3‑0.4mL/g进行调和,制备得到纳米氧化锌改性的可注射型磷酸钙骨水泥。纳米氧化锌易被生物体吸收,为人体提供必需微量元素,且本身具备良好的抗菌性,降低手术时发生细菌感染的风险。材料注射性良好,固化时间合适,抗菌性能优异,适用于微创手术,在临床骨修复领域具有广阔的应用前景。
Description
技术领域
本发明涉及一种生物医用材料技术领域的方法,具体是一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用,以α-TCP为粉末主体,以明胶为改性剂、纳米氧化锌为添加剂,制备得到注射性、抗菌性良好的可注射型磷酸钙骨水泥。
背景技术
可注射型骨水泥临床上常用于微创手术治疗,必须具备良好的可注射性、抗溃散性、生物相容性以及合适的固化时间。同时,材料固化后一般要求其力学强度至少达到人体松质骨的程度0.4~30.0 MPa [苗军, 王继芳, 中国修复重建外科杂志, 2005]。α-TCP是制备磷酸钙骨水泥的一种常见原料,与同类骨水泥相比,它的固化时间较快、强度较高、固化后孔隙率较大,通过加入合适的改性剂,可以具备良好的可注射性,适用于微创手术。明胶是胶原的水解产物,生物相容性好、无毒性反应、易降解、能被生物体代谢,在生物领域已被广泛地用于药物的载体和控释等方面。据文献报道,将明胶微球加入到骨水泥粉末中,在实现抗压强度提高的同时,还能改善骨水泥的自粘性、抗溃散性,可促进细胞的黏附、增殖、分化等行为,而且随明胶的降解而产生的孔隙,将有利于细胞、血管的长入和新骨的重建[Bigi A, et al, International Journal of Artificial Organs, 2004; Bigi A, etal, Biomaterials, 2004; Yin YJ, et al, Journal of Materials Science-Materialsin Medicine, 2003],本发明中采用溶液冻干法使明胶充分包覆于α-TCP粉末之上。
纳米氧化锌由于其粒径较小而具有穿透性,易被生物体吸收,作为生物体的必需微量元素,具有良好的生物相容性,在生物医学领域具有广阔的应用前景。同时,纳米氧化锌还具有良好的抗菌性,对大肠杆菌、金黄色葡萄球菌有很强的抑制作用,临床上有将其应用于牙齿粘结树脂,可有效预防继发龋齿,提升粘结树脂的性能[Lei Hua, et al,Journal of Coatings Technology and Research, 2010] ;纳米氧化锌还可以抑制癌细胞的生长,紫外照射可以增强其对癌细胞的杀伤作用。[郭大东, 博士学位论文,东南大学,2009]。基于纳米氧化锌的以上特点,以其作为骨水泥改性剂,一方面可以克服手术过程中的细菌感染,提高手术安全性;另一方面可以配合负载药物的骨水泥,辅助治疗细菌性骨科炎症、骨科肿瘤等骨科疾病,具有良好的使用前景。
本发明针对以上背景,提供一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法,通过改变明胶的复合方式,提高磷酸钙骨水泥的可注射性,纳米氧化锌作为添加剂不改变骨水泥固化性能的同时发挥其良好的抗菌性能。
发明内容
为克服现有技术的不足,本发明的目的在于提供一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥制备方法。
本发明的再一目的在于:提供上述方案获得的纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥产品。
本发明的又一目的在于提供上述纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥应用。
本发明目的通过下述方案实现,一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法,包含以下步骤:
(1)采用固相反应法将原料磷酸氢钙与碳酸钙按摩尔比2:1充分混合后,在1250-1400℃煅烧2-4h并急速冷却至室温,以无水乙醇为球磨介质400-450rpm进行球磨2-4h,制备α-TCP粉末;
(2)将α-TCP粉末按1g/2mL的比例加入质量分数为0.05-0.5%的明胶水溶液,使α-TCP粉末负载明胶质量分数为0.1-1%,1000-1500rpm高速搅拌0.5h后进行冷冻干燥,制备得到注射性能良好的明胶改性的α-TCP粉末;
(3)将纳米氧化锌按质量分数1-5%与明胶改性的α-TCP粉末充分混合,与固化液按液固比0.3-0.4mL/g进行调和,制备得到纳米氧化锌改性的可注射型磷酸钙骨水泥。
步骤(1)所述的固相反应法的原料混合方式为使用无水乙醇为介质的湿法球磨,球料比为质量比3:1,混合后的悬浊液置于130℃烘箱中干燥,干燥后的原料置于1250-1400℃马弗炉中高温煅烧2-4h,反应结束后取出,在鼓风环境中急速冷却,得到α-TCP粉末。
步骤(2)所述的明胶水溶液的配制方法为50℃加热下的搅拌溶解,搅拌方式为磁力搅拌或机械搅拌。
步骤(3)所述的纳米氧化锌粒径为30-100nm,与明胶改性的α-TCP粉末的混合方式为100-150rpm干法球磨。
本发明将传统的复合明胶的方式,由以微球形式添加至骨水泥粉末,改为先将骨水泥粉末分散于明胶溶液中,再通过冷冻干燥使明胶包覆于骨水泥粉末之上,使固化反应时骨水泥粉末在明胶的包覆下充分固化,提高骨水泥的可注射性和抗溃散性。纳米氧化锌直接负载在骨水泥粉末中,注射至体内后,可由骨水泥的孔隙中渗出,起到抗菌作用。
本发明还提供一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥,根据上述任一所述方法制备得到产品。
本发明也提供了纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的应用。
具体的制备步骤为:
1、将磷酸氢钙和碳酸钙按摩尔比2:1混合均匀。所述混合方式为超纯水为球磨介质下400-450rpm球磨混合,混合时间2-4h,混合后的悬浊液置于130℃烘箱中干燥,得干燥后的原料。
2、上述干燥后的原料置于1250-1400℃马弗炉中高温煅烧2-4h,反应结束后取出,在鼓风环境中急速冷却,得到α-TCP粉末。将产物以无水乙醇为球磨介质450rpm进行球磨2-4h,球磨后的悬浊液使用旋转蒸发仪除去乙醇,置于60℃烘箱中干燥过夜。
3、配制质量分数为0.05-0.5%的明胶水溶液。所述配制方法为50℃加热下的搅拌溶解,搅拌方式为磁力搅拌或机械搅拌。将球磨后的α-TCP粉末与上述明胶溶液按1g/2mL的比例混合,使α-TCP粉末负载明胶质量分数为0.1-1%,1000-1500rpm高速搅拌0.5h,进行冷冻干燥,制备得到明胶改性的α-TCP粉末。
4、将纳米氧化锌按质量分数1-5%与明胶改性的α-TCP粉末混合,混合方式为100-150rpm干法球磨,制备得到骨水泥粉末。
5、配制质量分数为2.5%的磷酸氢二钠水溶液。所述溶液的配制方式为室温下搅拌溶解,搅拌方式为磁力搅拌或机械搅拌。上述溶液作为骨水泥固化液储存备用。
6、将骨水泥固化液与粉末按液固比0.3-0.4mL/g进行调和,即可得到注射性良好的纳米氧化锌改性的可注射型磷酸钙骨水泥。
本发明的优点在于:
1、本发明以明胶为改性剂,采用溶液冻干的混合方式,使明胶与α-TCP粉末充分混合,改善体系的可注射性和抗溃散性。
2、将纳米氧化锌与粉末直接混合,使骨水泥具备抗菌性且不影响骨水泥的固化,纳米氧化锌发挥抗菌能力的同时也为生物体提供了必需的微量元素。本发明提供的制备方法简单,符合临床使用的需求,具有广阔的应用前景。
具体实施方式
以下实施例以发明技术方案为前提进行实施,给出了详细的实施方式和具体的操作过程,但本发明的保护范围并不限于下述的实施例。
(1)α-TCP粉末制备:
将磷酸氢钙粉末和碳酸钙粉末按摩尔比2:1称量,以总质量的1.5倍的超纯水为介质湿法球磨,转速400rpm,球磨时间4h,球磨珠与粉末质量比为3:1,球磨后置于130℃烘箱中干燥。将干燥后的粉末置于1400℃马弗炉中高温煅烧4h,反应结束后取出,在鼓风环境下急速冷却。将冷却后的粉末以1g/mL的比例加入无水乙醇湿法球磨,转速450rpm,球磨时间为4h,球磨珠与粉末质量比为4:1。粉末悬浊液使用旋转蒸发仪除去乙醇后置于60℃烘箱中充分干燥,制备得到α-TCP粉末。
(2)3.5.2 注射能力系数测试
将内径为20mm,末端开口内径2mm的20mL注射器垂直置于力学测试机平板上,将骨水泥粉末与固化液按一定合适比例混合均匀置于注射器中,于混合后120s时进行测试。以速率15mm/min推进将骨水泥推出,直至最大推进力为100N时停止。将推出的骨水泥重量占总重量的百分比作为注射能力系数。
(3)抗菌试验测试:
骨水泥调和后填入φ6*12cm3模具,置于37℃100%湿度环境中充分固化24h。参照标准GB/T21510-2008附录B测试材料抗菌性,以大肠杆菌为测试菌种。取培养三代以上的大肠杆菌,用PBS缓冲溶液稀释至适宜浓度(约为105cfu/mL);称取抗菌骨水泥1.0g±0.05g放入三角瓶中,加入95mL含0.1%吐温-80的PBS混合后,再加入5.0mL上述预制菌悬液。对照组按上述方法配制不含抗菌骨水泥的菌悬液。将试验组和对照组置于37℃150rpm恒温摇床中振荡孵育2-4h。振荡结束后,试验组和对照组经过适当的稀释,接种于含有琼脂培养基的平皿上,每个浓度设置2个平行样,将上述平皿于37℃培养箱中培养24h,做活菌培养计数。
实施例1
称取0.2g明胶溶解于40mL超纯水中,50℃加热搅拌促进溶解,然后向水溶液中加入20g实施例上述(1)所制α-TCP粉末,1500rpm高速搅拌0.5h后用液氮快速冷冻,进行冷冻干燥48h以上。干燥后的粉末用粉碎机粉碎,添加质量分数3%的纳米氧化锌,其粒径为70nm,150rpm干法球磨2h,制备得到骨水泥粉末。配制质量分数为2.5%的磷酸氢二钠水溶液作为固化液,将固化液与骨水泥粉末按液固比0.35mL/g进行调和,参照标准ASTM C191测定初凝时间为7min,终凝时间为21min;按实上述(2)测试注射能力系数为95%,水中不溃散;按上述(3)测试材料抗菌性,结果为空白组菌落数为3.31*109cfu/mL,试验组菌落数为2.45*108cfu/mL,抗菌率为92.6%。
实施例2
称取0.1g明胶溶解于40mL超纯水中,50℃加热搅拌促进溶解,然后向水溶液中加入20g上述(1)所制α-TCP粉末,1500rpm高速搅拌0.5h后用液氮快速冷冻,进行冷冻干燥48h以上。干燥后的粉末用粉碎机粉碎,添加质量分数5%的纳米氧化锌,其粒径为70nm,150rpm干法球磨2h,制备得到骨水泥粉末。配制质量分数为2.5%的磷酸氢二钠水溶液作为固化液,将固化液与骨水泥粉末按液固比0.35mL/g进行调和,参照标准ASTM C191测定初凝时间为8min,终凝时间为22min;按上述(2)测试注射能力系数为93%,水中不溃散;按上述(3)测试材料抗菌性,结果为空白组菌落数为1.27*109cfu/mL,试验组菌落数为1.0 *107cfu/mL,抗菌率为99.2%。
实施例3
称取0.1g明胶溶解于40mL超纯水中,50℃加热搅拌促进溶解,然后向水溶液中加入20g上述(1)所制α-TCP粉末,1500rpm高速搅拌0.5h后用液氮快速冷冻,进行冷冻干燥48h以上。干燥后的粉末用粉碎机粉碎,添加质量分数8%的纳米氧化锌,其粒径为70nm,150rpm干法球磨2h,制备得到骨水泥粉末。配制质量分数为2.5%的磷酸氢二钠水溶液作为固化液,将固化液与骨水泥粉末按液固比0.35mL/g进行调和,参照标准ASTM C191测定初凝时间为10min,终凝时间为25min;按上述(2)测试注射能力系数为95%,水中不溃散;按上述(3)测试材料抗菌性,结果为空白组菌落数为3.14*109cfu/mL,试验组菌落数为1.0 *107cfu/mL,抗菌率为99.7%。
Claims (2)
1.纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法,其特征在于,包含以下步骤:
(1)采用固相反应法将原料磷酸氢钙与碳酸钙按摩尔比2:1充分混合后,在1250-1400℃煅烧2-4h并急速冷却至室温,以无水乙醇为球磨介质450rpm进行球磨2-4h,制备α-TCP粉末;
(2)将α-TCP粉末按1g/2mL的比例加入质量分数为0.05-0.5%的明胶水溶液,使α-TCP粉末负载明胶质量分数为0.1-1%,1000-1500rpm高速搅拌0.5h后进行冷冻干燥,制备得到注射性能良好的明胶改性的α-TCP粉末;
(3)将纳米氧化锌按质量分数1-5%与明胶改性的α-TCP粉末充分混合,与固化液按液固比0.3-0.4mL/g进行调和,制备得到纳米氧化锌改性的可注射型磷酸钙骨水泥;
步骤(1)所述的固相反应法的原料混合方式为使用无水乙醇为介质的湿法球磨,转速为400rpm,球磨时间为2-4h,球料比为质量比3:1;
步骤(2)所述的明胶水溶液的配制方法为50℃加热下的搅拌溶解,搅拌方式为磁力搅拌或机械搅拌;
步骤(3)所述的纳米氧化锌粒径为30-100nm,与明胶改性的α-TCP粉末的混合方式为100-150rpm干法球磨。
2.一种纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥,其特征在于根据权利要求1所述方法制备得到。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710976341.6A CN107812240B (zh) | 2017-10-19 | 2017-10-19 | 纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710976341.6A CN107812240B (zh) | 2017-10-19 | 2017-10-19 | 纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107812240A CN107812240A (zh) | 2018-03-20 |
CN107812240B true CN107812240B (zh) | 2021-04-09 |
Family
ID=61607404
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710976341.6A Active CN107812240B (zh) | 2017-10-19 | 2017-10-19 | 纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107812240B (zh) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111991615A (zh) * | 2020-08-11 | 2020-11-27 | 上海纳米技术及应用国家工程研究中心有限公司 | 镧系元素掺杂的可注射型磷酸钙骨水泥的制备方法及其产品和应用 |
CN114106397A (zh) * | 2021-11-09 | 2022-03-01 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种低模量多孔pmma仿生骨水泥的制备方法及其产品和应用 |
CN114053476B (zh) * | 2021-11-30 | 2022-11-25 | 西华师范大学 | 一种抗菌磷酸镁骨水泥及其制备方法和用途 |
CN114225108A (zh) * | 2021-12-17 | 2022-03-25 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种高黏度防渗漏pmma骨水泥的制备方法及其产品和应用 |
CN114345492A (zh) * | 2021-12-27 | 2022-04-15 | 深圳市金阳盛城市服务集团有限公司 | 一种智能垃圾处理设备以及垃圾处理方法 |
CN115068694A (zh) * | 2022-05-16 | 2022-09-20 | 昆明理工大学 | 一种活性可注射骨水泥修复材料的制备方法 |
CN115671394A (zh) * | 2022-11-23 | 2023-02-03 | 国纳之星(上海)纳米科技发展有限公司 | 一种负载植物外泌体的可注射型磷酸钙骨水泥的制备及其产品和应用 |
CN115737932B (zh) * | 2022-11-23 | 2024-04-26 | 国纳之星(上海)纳米科技发展有限公司 | 负载x射线诱导光动力治疗/放疗协同诊疗一体化探针的骨水泥的制备及产品和应用 |
CN115887756A (zh) * | 2022-12-12 | 2023-04-04 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种负载中药提取物的可注射型磷酸钙骨水泥的制备及其产品和应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06296679A (ja) * | 1993-04-12 | 1994-10-25 | Nitta Gelatin Inc | 医科歯科用セメント材料 |
EP1380313A1 (en) * | 2002-07-11 | 2004-01-14 | MERCK PATENT GmbH | Method of preparing porous calcium phosphate morsels and granules via Gelatin processing |
CN101564556A (zh) * | 2009-05-15 | 2009-10-28 | 天津大学 | 明胶微球/磷酸钙骨水泥复合的多级释药载体的制备方法 |
CN106581749A (zh) * | 2016-12-20 | 2017-04-26 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种温敏性peg聚酯嵌段共聚物改性的可注射型磷酸钙骨水泥及制备和应用 |
CN106620840A (zh) * | 2016-12-27 | 2017-05-10 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种丝素蛋白改性的骨水泥多孔支架及制备和应用 |
CN106729971A (zh) * | 2016-11-23 | 2017-05-31 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种水溶性单壁碳纳米管改性的磷酸钙骨水泥及制备和应用 |
-
2017
- 2017-10-19 CN CN201710976341.6A patent/CN107812240B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06296679A (ja) * | 1993-04-12 | 1994-10-25 | Nitta Gelatin Inc | 医科歯科用セメント材料 |
EP1380313A1 (en) * | 2002-07-11 | 2004-01-14 | MERCK PATENT GmbH | Method of preparing porous calcium phosphate morsels and granules via Gelatin processing |
CN101564556A (zh) * | 2009-05-15 | 2009-10-28 | 天津大学 | 明胶微球/磷酸钙骨水泥复合的多级释药载体的制备方法 |
CN106729971A (zh) * | 2016-11-23 | 2017-05-31 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种水溶性单壁碳纳米管改性的磷酸钙骨水泥及制备和应用 |
CN106581749A (zh) * | 2016-12-20 | 2017-04-26 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种温敏性peg聚酯嵌段共聚物改性的可注射型磷酸钙骨水泥及制备和应用 |
CN106620840A (zh) * | 2016-12-27 | 2017-05-10 | 上海纳米技术及应用国家工程研究中心有限公司 | 一种丝素蛋白改性的骨水泥多孔支架及制备和应用 |
Non-Patent Citations (4)
Title |
---|
Effect of added gelatin on the properties of calcium phosphate cement;A. Bigi等;《Biomaterials》;20040630;第25卷(第14期);2893-2898 * |
Optimization of a biomimetic bone cement: Role of DCPD;Silvia Panzavolta等;《Journal of Inorganic Biochemistry》;20110831;第105卷(第8期);1060-1065 * |
Preparation of calcium phosphate cement with an improved setting behavior;Hidero Unum等;《Journal of Asian Ceramic Societies》;20130331;26-29 * |
纳米氧化锌在骨科中的应用前景;廖航等;《中国矫形外科杂志》;20170930;第25卷(第18期);1675-1677 * |
Also Published As
Publication number | Publication date |
---|---|
CN107812240A (zh) | 2018-03-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107812240B (zh) | 纳米氧化锌改性的抗菌可注射型磷酸钙骨水泥的制备方法及其产品和应用 | |
Ignjatović et al. | Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues | |
Zhang et al. | A novel composite scaffold comprising ultralong hydroxyapatite microtubes and chitosan: preparation and application in drug delivery | |
Liu et al. | Multifunctional injectable protein-based hydrogel for bone regeneration | |
CN100563727C (zh) | 一种纳米羟基磷灰石/丝素蛋白-壳聚糖复合支架的制备方法 | |
CN107899073B (zh) | 骨水泥、其制备方法和用途 | |
CN111671969B (zh) | 一种可注射椎体强化磷酸镁骨水泥及其制备方法 | |
Cao et al. | Porous ZnO modified silk sutures with dual light defined antibacterial, healing promotion and controlled self-degradation capabilities | |
CN110787324A (zh) | 一种药物控释型聚乳酸基骨修复支架材料的制备方法 | |
CN101011598A (zh) | 一种生物活性的止血、骨缺损修复材料 | |
CN115350334A (zh) | 一种聚酰亚胺基复合气凝胶材料的制备方法、产品及应用 | |
CN107754020A (zh) | 壳聚糖季铵盐改性抗菌磷酸钙骨水泥的制备方法及其产品和应用 | |
CN107569719B (zh) | Ct造影剂改性可注射型骨水泥制备方法及其产品和应用 | |
Yang et al. | Co-exchanged montmorillonite: a potential antibacterial agent with good antibacterial activity and cytocompatibility | |
CN107970489A (zh) | 载药有机磷酸锆改性的可注射型骨水泥的制备方法及其产品和应用 | |
CN107569717B (zh) | 具有组织增氧功能的骨修复材料及其应用 | |
CN107715171A (zh) | 快速降解的药物控释可注射型骨水泥的制备方法及其产品和应用 | |
TW201345570A (zh) | 抗菌含鈣材料 | |
Sharifi et al. | Cell-loaded genipin cross-linked collagen/gelatin skin substitute adorned with zinc-doped bioactive glass-ceramic for cutaneous wound regeneration | |
CN105536059A (zh) | 一种自修复可注射骨水泥及制备方法 | |
CN110507851A (zh) | 一种可吸收骨蜡及其制备方法 | |
Govindaraj et al. | Mineral-substituted hydroxyapatite reinforced poly (raffinose-citric acid)–polyethylene glycol nanocomposite enhances osteogenic differentiation and induces ectopic bone formation | |
AU2021100655A4 (en) | POLY γ-GLUTAMIC ACID/CHITOSAN/CALCIUM CITRATE BIOMATERIAL AND PREPARATION METHOD THEREO | |
CN1242818C (zh) | 一种可降解的复合支架材料及其制备方法 | |
CN110721336A (zh) | 一种纳米硅酸镁锂/聚己内酯复合材料及制备方法 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240117 Address after: Building C, No. 888 Huanhu West Second Road, Pudong New Area, Shanghai, April 2012 Patentee after: Guona Star (Shanghai) Nanotechnology Development Co.,Ltd. Address before: 200241 No. 28 East Jiangchuan Road, Shanghai, Minhang District Patentee before: SHANGHAI NATIONAL ENGINEERING RESEARCH CENTER FOR NANOTECHNOLOGY Co.,Ltd. |