CN108379658B - 具有含铜涂层的骨科植入器件及其制备方法 - Google Patents
具有含铜涂层的骨科植入器件及其制备方法 Download PDFInfo
- Publication number
- CN108379658B CN108379658B CN201810117480.8A CN201810117480A CN108379658B CN 108379658 B CN108379658 B CN 108379658B CN 201810117480 A CN201810117480 A CN 201810117480A CN 108379658 B CN108379658 B CN 108379658B
- Authority
- CN
- China
- Prior art keywords
- copper
- implant device
- orthopedic implant
- coating
- microspheres
- 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
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims abstract description 111
- 229910052802 copper Inorganic materials 0.000 title claims abstract description 109
- 239000010949 copper Substances 0.000 title claims abstract description 109
- 238000000576 coating method Methods 0.000 title claims abstract description 97
- 239000011248 coating agent Substances 0.000 title claims abstract description 92
- 239000007943 implant Substances 0.000 title claims abstract description 64
- 230000000399 orthopedic effect Effects 0.000 title claims abstract description 63
- 238000004519 manufacturing process Methods 0.000 title description 2
- 239000004005 microsphere Substances 0.000 claims abstract description 66
- 229920000642 polymer Polymers 0.000 claims abstract description 19
- 239000000126 substance Substances 0.000 claims abstract description 11
- 239000000243 solution Substances 0.000 claims description 24
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 21
- 229910001431 copper ion Inorganic materials 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 19
- 238000003756 stirring Methods 0.000 claims description 15
- 229920001661 Chitosan Polymers 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 229910001069 Ti alloy Inorganic materials 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 229920002721 polycyanoacrylate Polymers 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- -1 polytrimethylene carbonate Polymers 0.000 claims description 6
- 238000002390 rotary evaporation Methods 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000005312 bioglass Substances 0.000 claims description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 229920001688 coating polymer Polymers 0.000 claims description 4
- 150000001879 copper Chemical class 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 238000000593 microemulsion method Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- 229920001610 polycaprolactone Polymers 0.000 claims description 4
- 239000004632 polycaprolactone Substances 0.000 claims description 4
- 239000004626 polylactic acid Substances 0.000 claims description 4
- 229920000166 polytrimethylene carbonate Polymers 0.000 claims description 4
- 238000005507 spraying Methods 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 238000002386 leaching Methods 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000006228 supernatant Substances 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 102000008186 Collagen Human genes 0.000 claims description 2
- 108010035532 Collagen Proteins 0.000 claims description 2
- JJLJMEJHUUYSSY-UHFFFAOYSA-L Copper hydroxide Chemical compound [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 claims description 2
- 239000005750 Copper hydroxide Substances 0.000 claims description 2
- 239000005752 Copper oxychloride Substances 0.000 claims description 2
- 229920000858 Cyclodextrin Polymers 0.000 claims description 2
- 229910000861 Mg alloy Inorganic materials 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 2
- 239000003462 bioceramic Substances 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 238000001023 centrifugal evaporation Methods 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- HKMOPYJWSFRURD-UHFFFAOYSA-N chloro hypochlorite;copper Chemical compound [Cu].ClOCl HKMOPYJWSFRURD-UHFFFAOYSA-N 0.000 claims description 2
- 229920001436 collagen Polymers 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 229910001956 copper hydroxide Inorganic materials 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- JJKSAEHNIHMQKQ-UHFFFAOYSA-N copper;quinoline Chemical compound [Cu].N1=CC=CC2=CC=CC=C21 JJKSAEHNIHMQKQ-UHFFFAOYSA-N 0.000 claims description 2
- 229920006237 degradable polymer Polymers 0.000 claims description 2
- 238000009826 distribution Methods 0.000 claims description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 2
- 238000010907 mechanical stirring Methods 0.000 claims description 2
- 230000010355 oscillation Effects 0.000 claims description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 claims description 2
- 239000004584 polyacrylic acid Substances 0.000 claims description 2
- 229920000515 polycarbonate Polymers 0.000 claims description 2
- 239000004417 polycarbonate Substances 0.000 claims description 2
- 229920002635 polyurethane Polymers 0.000 claims description 2
- 239000004814 polyurethane Substances 0.000 claims description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- LITQZINTSYBKIU-UHFFFAOYSA-F tetracopper;hexahydroxide;sulfate Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Cu+2].[Cu+2].[Cu+2].[Cu+2].[O-]S([O-])(=O)=O LITQZINTSYBKIU-UHFFFAOYSA-F 0.000 claims description 2
- 239000010936 titanium Substances 0.000 claims description 2
- 229910052719 titanium Inorganic materials 0.000 claims description 2
- 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 claims description 2
- 210000000988 bone and bone Anatomy 0.000 abstract description 48
- 208000015181 infectious disease Diseases 0.000 abstract description 16
- 238000002513 implantation Methods 0.000 abstract description 11
- 230000035876 healing Effects 0.000 abstract description 10
- 238000007306 functionalization reaction Methods 0.000 abstract description 2
- 238000002464 physical blending Methods 0.000 abstract description 2
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
- 230000009881 electrostatic interaction Effects 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 description 24
- 230000008827 biological function Effects 0.000 description 18
- 230000007547 defect Effects 0.000 description 17
- 239000010410 layer Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 230000011164 ossification Effects 0.000 description 10
- 208000010392 Bone Fractures Diseases 0.000 description 7
- 206010017076 Fracture Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 238000002156 mixing Methods 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000945 filler Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 210000004969 inflammatory cell Anatomy 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 206010031252 Osteomyelitis Diseases 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 229960001701 chloroform Drugs 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 238000000889 atomisation Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 229910000365 copper sulfate Inorganic materials 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000000963 osteoblast Anatomy 0.000 description 2
- 229920000070 poly-3-hydroxybutyrate Polymers 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 206010043827 tibia fracture Diseases 0.000 description 1
- 229910021654 trace metal Inorganic materials 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
Images
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
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
-
- 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
- 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
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
- A61L2300/622—Microcapsules
-
- 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
-
- 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
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)
- Prostheses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了一种具有含铜涂层的骨科植入器件。将不同浓度的载铜微球通过一定的方式梯度化地固定/分散在骨科植入器件表面的聚合物载体中,从而可实现骨科植入器件的生物功能化。其中,功能化载铜微球的固定方式包括化学接枝、物理共混、静电作用等。这种具有生物功能化含铜涂层的骨科植入器件植入体内后可以促进骨组织愈合、促进新生血管生成、抑制细菌感染,从而避免因骨科植入器件植入后的感染问题,并加速受损骨组织的愈合。
Description
技术领域
本发明涉及骨科植入类医疗器械领域,特别提供一种能够固定骨折部位或填充骨缺损部位的、具有抗感染、促成骨、促血管化等生物功能的含铜涂层骨科植入器件。
背景技术
骨科植入类器件(Orthopedic implant devices),用以固定骨折部位、充填骨缺损腔或骨植入器件与骨床间空隙的器件(材料)。其作用是加速骨缺损愈合或使骨植入器件固定。随着人口老龄化的不断发展,并伴随着生活/工作节奏的加快,全球范围内发生骨折外伤、骨肿瘤、关节类疾病的比例呈逐年上升的趋势,由此引发的骨感染数量激增。虽然大量抗生素已用于治疗骨感染,但随着耐药菌的增多,骨感染的治疗难度加大,增大病患的痛苦。
目前临床应用的骨科植入类器件多为惰性材料,即不具备生物活性(促成骨性、促血管化等)。而具有生物活性的骨科植入类器件可以实现加速骨组织愈合,提高器件植入成功率的功效,是目前研究的热点。
铜是人体中必需的一种微量金属元素。研究证明,10-6M浓度的铜离子即可展示出强有力的杀菌功能,而当浓度达到10-4M时对人体正常组织细胞也并无影响,这就为铜离子提供了一个较大的适用浓度范围,在既保证其生物功能的同时,还具备最基本的生物安全性。中科院金属研究所的杨柯等人将铜加入到317L不锈钢中,体内外实验均表明,含铜不锈钢具有明显的抗菌和抑制细菌生物膜形成的效果。
此外,铜离子还具有促进成骨细胞增殖及促进新生血管生成等多重生理功能。
为了解决上述问题,本申请提出一种具有多重生物功能的含铜涂层,其具有良好的抗感染、促成骨、促血管化的作用。因此,在骨科植入器件表面制备含铜涂层,可持久发挥铜的生物效应,实现骨科器件置入后抗感染、促成骨、促新生血管化等多重生物功能,从而缩短骨组织愈合周期。本发明是针对骨科植入器件,为解决其置入体内可能引发的感染及生物惰性等问题,提出在骨科植入器件表面制备具有抗感染、促成骨、促血管化等多重生物功能的含铜涂层,在保证器件现有安全性、支撑作用的前提下,降低骨可植入器件发生感染及相关并发症的发生概率。
发明内容
本发明的目的是在保证骨科植入器件在置入骨缺损部位后对缺损部位进行一定的力学支撑的基础上,在骨科植入器件表面制备一种具有生物功能的含铜涂层,以实现骨科植入器件在置入后的抗感染、促成骨及促血管化等多重生物功能。
本发明技术方案如下:
一种具有含铜涂层的骨科植入器件,其特征在于:在骨科植入器件表面涂覆有含铜聚合物涂层,该涂层中含有铜元素。
作为优选的技术方案:
所述具有含铜涂层的骨科植入器件,其特征在于,骨科植入器件所用材料包括硫酸钙、磷酸钙、生物玻璃、生物陶瓷、羟基磷灰石、钛及钛合金、不锈钢、可降解镁及镁合金、聚乳酸等等。
所述具有含铜涂层的骨科植入器件,其特征在于:所述铜元素通过载铜微球添加,载铜微球为直径尺寸在50-500nm的可降解聚合物包衣微球。
所述具有含铜涂层的骨科植入器件,其特征在于:载铜微球的微球基质材料为具有良好成膜性、生物相容性及可降解性的聚合物,如聚三亚甲基碳酸酯(PTMC)、聚氰基丙烯酸酯(PACA)、聚羟基烷基醇酯(PHAs)、PHB(聚-3-羧基丁酸酯)、聚乙交酯-丙交酯共聚物(PLGA)、聚己内酯(PCL)、聚丙烯酸、纤维素、壳聚糖等之一种或多种,所载含铜物质为纳米级金属铜粉、无机铜离子、含铜有机物之一种或多种。
所述具有含铜涂层的骨科植入器件,其特征在于:所述纳米级金属铜粉的尺寸在10-200nm的范围内,无机铜离子来自碱式硫酸铜、氧氯化铜、氢氧化铜之一种或多种,含铜有机物为乙酸铜、氨基酸铜、喹啉铜之一种或多种。
所述具有含铜涂层的骨科植入器件,其特征在于:载铜微球中,基质材料与含铜物质的摩尔比在100:1-2:1的范围内。
所述具有含铜涂层的骨科植入器件,其特征在于:所述铜元素浓度呈梯度化分布在涂层聚合物中;所述聚合物为壳聚糖及其衍生物、聚氨酯、环糊精、淀粉、纤维素、海藻酸钠、胶原、聚乳酸、聚乙二醇、聚碳酸酯等合成聚合物及天然聚合物之一种或多种。
所述具有含铜涂层的骨科植入器件,其特征在于:所述含铜聚合物涂层厚度小于等于5μm。
所述骨科植入器件的制备方法,其特征在于:铜元素在骨科植入表面涂层聚合物中的分布方式为:以载铜微球的形式,通过分层制备法将载铜微球梯度分散在聚合物涂层中。
所述骨科植入器件的制备方法,其特征在于,包括以下步骤:
步骤一:采用微乳液法制备载铜微球。
步骤二:制备不同配比的载铜微球聚合物溶液,通过浸提或喷涂法逐层制备具有载铜微球的聚合物涂层。
所述骨科植入器件的制备方法,其特征在于,步骤二中采用微乳液法制备载铜微球包括以下步骤:
(1)配制质量体积浓度为5-150mg/mL的铜盐水溶液;
(2)配制质量体积浓度为5-900mg/mL的微球基质溶液,溶剂为体积比三氯甲烷:丙酮=1:4—4:1;
(3)配制质量体积浓度为1-200mg/mL的PVA水溶液;
(4)将铜盐水溶液加入微球基质溶液中,搅拌均匀后将混合液加入PVA水溶液中;
(5)采用机械搅拌或超声震荡的方法制备不同粒度的微球,其中,搅拌转数在500-5000rpm的范围内,搅拌时间为2-10h;超声功率在50-100W的范围内,超声时间为5-25min;
(6)利用离心或旋转蒸发的方法收集反应制得的微球,其中:
离心法所采取的转数为500-2000rpm,离心后去除上清液,将微球沉淀在蒸馏水中悬浮清洗,干燥;
旋转蒸发法所采取的转速为10-50rpm,将沉降一定时间的溶液,去上清液,将下层反应液加入旋转蒸发仪中,发生温度为30-45℃,时间为30min-2h。
本发明的设计思想:
在骨科植入器件表面制备具有生物功能的含铜涂层,涂层应均匀分布在器件的各个位置,以确保骨科植入器件置入后,发挥抗感染、促成骨、促血管化等生物功能。将不同浓度的载铜微球,采用物理共混、化学接枝或静电吸附的方法在骨科植入器件表面逐层制备含铜涂层,使涂层铜含量具有梯度化特点,涂层载体为医用级可降解高分子材料(含铜涂层示意图见附图2)。载铜微球制备时,微球壳体材料应为可生物降解,成膜性良好并具有良好生物相容性的高分子材料。涂层制备过程中,通过调节微球中含铜量或涂层所含微球的量,构建梯度化含铜涂层。涂层制备过程中,对骨科植入器件结构应不造成破坏,从而实现骨科植入器件对缺损部位的有效支撑,以及抗感染、促成骨、促血管化等生物功能。
本发明的特点及有益效果在于:
1.本发明提供的一种具有生物功能的含铜涂层骨科植入器件,使其具有抗感染、促成骨、促血管化等多重生物功能。
2.本发明涉及的具有生物功能的含铜涂层,可替代目前骨科植入器件所采用的抗生素药物涂层。含铜涂层具有抗感染的特性,可避免因药物涂层引起的细菌耐药性的问题。
3.本发明不但可以作为一种生物功能化“药物涂层”,还具有促成骨、促血管化的生物功能,从而缩短骨组织愈合周期,增加骨科植入器件的使用成功率。
附图说明
图1载铜微球形貌示意图。
图2具有梯度化载铜微球的生物功能化含铜涂层的示意图。
具体实施方式
以下实施例将对本发明予以进一步的说明,但并不因此而限制本发明。
实施例1
逐层化学接枝法在骨科植入器件上制备具有梯度化载铜微粒的涂层:
采用逐层化学接枝法将具有羟基、羧基等活性官能团的载铜微球固定在具有氨基和羟基的天然可降解壳聚糖聚合物上,每层所载铜的量呈梯度化,通过涂层梯度化释放铜离子,实现含铜涂层的生物功能化可调控。
(1)载铜微球的制备
①称取0.05g、0.2g和0.5gCuCl2,并分别溶解于5mL蒸馏水中配制三种均一溶液;
②再将1.0gPACA溶于三氯甲烷和丙酮的混合溶液中(其中,三氯甲烷:丙酮的体积比为3:2),配制出质量体积浓度为100mg/mL的PACA有机溶液;
③称取PVA1.0g,溶解于蒸馏水中,配制出质量体积浓度为20mg/mL的PVA水溶液,混匀待用;
④将CuCl2水溶液缓慢滴入PACA有机溶液中,混合均匀,再将上述混合液加入PVA水溶液中,磁力搅拌,转数为500rpm,搅拌8小时;超声功率在50-100W的范围内,超声时间为5min;
⑤反应液静置2小时,去上清液,将下层沉淀转入旋转蒸发仪中,在30摄氏度下,旋蒸30分钟,得大量微球粉末。
同法制备不同载铜量的载铜微球,差别在于称取CuCl2的质量分别为0.2g和0.5g,得梯度浓度的微球,微球形貌见附图1。
(2)梯度化载铜聚合物涂层的制备
①配制1%醋酸溶液
取1mL的冰醋酸试剂于100ml容量瓶中,向其中缓慢加入蒸馏水,并定容,混匀待用。
②配制1%壳聚糖溶液
准确称取壳聚糖粉末1g,将100ml配制好的醋酸溶液与粉末混匀,静置24小时,除气泡待用。
③单层载铜涂层的制备
通过超声雾化喷涂或浸提的方法在骨科植入器件(由钛合金制成)上制备壳聚糖涂层,涂层厚度约1μm,待涂层干燥后,在EDC/NHS催化作用下,将低浓度的载铜微球接枝到壳聚糖涂层上。
④具有梯度化载铜微球涂层的制备
重复单层载铜涂层的制备方法,在骨科植入器件表面逐层制备不同载铜浓度的载铜微球涂层。涂层总厚度控制在5μm以内。
(3)动物实验
将具有生物功能含铜涂层的钛合金骨钉/骨板植入兔子股骨断裂模型处,以含铜钛合金骨钉/骨板作为对照组。植入30天后通过X射线成像观察骨折部位骨组织愈合情况,与对照组相比,应用具有含铜涂层的钛合金骨钉/骨板的骨折部位,骨组织愈合明显,原断裂部位骨痂增生程度较小。随后处死动物并取出带有骨钉/骨板的骨折段,通过硬组织切片,染色观察骨折处周围组织发生炎症的情况,结果表明,植入具有含铜涂层的骨钉/骨板周围组织未发生炎性细胞浸润,而对照组骨钉/骨板周围组织出现少量炎性细胞浸润。因此,具有梯度化含铜涂层骨科植入器件(骨钉/骨板)表现出快速骨组织愈合、抗菌、抗炎等特性,其抗菌性明显优于可以释放铜离子的含铜金属材料。
实施例2
逐层静电吸附法在骨科植入器件上制备具有梯度化载铜微球的涂层:
(1)配制带负电荷的透明质酸钠的水溶液(浓度1-5%),通过浸提法在生物玻璃块状骨填充物上制备透明质酸涂层;
(2)载铜微球的制备
①称取0.20g壳聚糖于250m L单口圆底烧瓶中,加入2%(质量分数)醋酸溶液250mL,开启电动搅拌装置缓慢搅拌直至壳聚糖完全溶解。
②边搅拌边加入Span-80 0.4mL和Tween-80 0.6mL,继续搅拌30min使之形成均匀、透明、稳定的微乳液。接着加入0.05g硫酸铜粉末,高速搅拌使之扩散均匀;
③缓慢滴加1mol·L-1的NaOH溶液,同时匀速搅拌,用PHS-3B型精密pH计(中国上海雷磁)在25℃下检测体系pH值的变化,直至微碱性(p H值为7.20);
④NaOH溶液滴加完毕后,中速搅拌并加入0.30g柠檬酸三钠,继续搅拌3h,使乳液中形成的壳聚糖微球交联固化,得到的透明乳液用离心机离心分离;
⑤将下层沉淀转入旋转蒸发仪中,在30摄氏度下,旋蒸30分钟,得大量微球粉末。
同法制备不同载铜量的载铜微球,差别在于称取CuSO4的质量分别为0.2g和0.5g,得梯度浓度的微球。
(3)梯度化载铜聚合物涂层的制备
将带有负电性透明质酸涂层的生物玻璃骨填充物浸入具有正电性低浓度载铜微球的水溶液中,微球将通过静电作用固定于透明质酸涂层上。
重复以上单层涂层的制备方法,构建具有梯度化(含铜量逐层递增模式)载铜微球的聚合物涂层。
(4)亲水性外层的制备
在载有梯度化载铜微球的聚合物涂层外,通过超声雾化喷涂法制备一层<1μm聚乙二醇涂层。
(5)含铜涂层的表征
将带有含铜涂层的生物玻璃骨填充材料置入兔子股骨缺损模型处,以无含铜涂层的生物玻璃骨填充材料作为对照组,植入15天取材,通过μ-CT对实验组和对照组的骨缺损部位进行扫描。实验结果表明,具有含铜涂层的骨科植入器件在植入15天后,缺损部位未见感染现象发生,而对照组,缺损部位则被大量炎性细胞浸润;实验组缺损部位在骨填充物周围形成大量新生骨组织,并已有新生血管爬升;而对照组骨缺损部位新生骨组织与实验组相比较少,未见新生血管。因此,本发明具有生物功能的含铜涂层的骨科植入器件表现出抗感染、促成骨、促血管化等特性。
对比例3
将实施例2中制备的具有梯度化载铜微球含铜涂层的制备方法与已申请的发明专利“一种生物可降解含铜涂层纯镁吻合钉及其制备”(专利公开号为:CN 103110977A)中提供的表面涂镀铜离子涂层的方法进行对比,通过对比两种方法制备的涂层在体外的离子溶出性能,以及在体内的植入情况,评价两种方法制备的含铜涂层的安全性和有效性。
由实施例2可知,本发明具有梯度化载铜微球的含铜涂层,可实现器件植入初期,从涂层中释放足以表达生物功能的铜离子浓度,并通过涂层设计、载铜微球载铜量的微调来确保铜离子释放量在生物安全范围内;涂层通过初期释放的铜离子来实现抗菌,促进骨组织愈合(即促进成骨细胞增殖与迁移),从而实现避免骨内感染,重建骨组织结构功能。植入后期,通过微量铜离子的释放促进新生血管生成,以满足骨组织后期重建过程中的养分供给。
而根据已申请的专利中提供的涂镀铜离子涂层,则不具有铜离子梯度释放的效果,铜离子的释放量只依赖于涂层载体的性质,如用水溶性或降解速率很快的载体,则植入过程中,涂层中的铜就可能已经释放,当到达目标位置时,已没有足够的铜离子作用于周围组织;如用降解速率慢的载体,则植入后初期没有足够的铜离子释放来实现其多重生物功能性。
将根据实施例2制得的具有梯度化含铜涂层的钛合金骨钉骨板植入兔子胫骨骨折模型部位,以已申请的专利制备的不具有铜离子梯度释放的钛合金骨钉骨板为对照组,进行动物实验对比。植入15天取材,通过μ-CT对实验组和对照组的骨缺损部位进行扫描。实验结果表明,具有含铜涂层的骨科植入器件在植入15天后,缺损部位未见感染现象发生,而对照组,缺损部位则被少量炎性细胞浸润;实验组缺损部位在骨填充物周围形成大量新生骨组织,并已有新生血管爬升;而对照组骨缺损部位新生骨组织与实验组相比较少,未见新生血管。因此,本发明具有生物功能的含铜涂层的骨科植入器件表现出抗感染、促成骨、促血管化等特性。
以上实验结果及分析表明,本发明权利要求中申请保护的具有梯度化载铜微球涂层及其制备方法具有明显的优异效果。
Claims (9)
1.一种具有含铜涂层的骨科植入器件,其特征在于:在骨科植入器件表面涂覆有含铜聚合物涂层,该涂层中含有铜元素;所述铜元素通过载铜微球添加,铜元素在骨科植入器件表面涂层聚合物中的分布方式为:以载铜微球的形式,通过分层制备法将载铜微球分散在聚合物涂层中,铜元素浓度呈梯度化分布在涂层聚合物中。
2.按照权利要求1所述具有含铜涂层的骨科植入器件,其特征在于,骨科植入器件所用材料为硫酸钙、磷酸钙、生物玻璃、生物陶瓷、羟基磷灰石、钛及钛合金、不锈钢、可降解镁及镁合金、聚乳酸之一种或多种。
3.按照权利要求1所述具有含铜涂层的骨科植入器件,其特征在于:载铜微球为直径在50-500nm的可降解聚合物包衣微球。
4.按照权利要求3所述具有含铜涂层的骨科植入器件,其特征在于:载铜微球的微球基质材料为聚三亚甲基碳酸酯(PTMC)、聚氰基丙烯酸酯(PACA)、聚羟基烷基醇酯(PHAs)、PHB(聚-3-羧基丁酸酯)、聚乙交酯-丙交酯共聚物(PLGA)、聚己内酯(PCL)、聚丙烯酸、纤维素、壳聚糖之一种或多种;所载含铜物质为纳米级金属铜粉、无机铜离子、含铜有机物之一种或多种,纳米级金属铜粉的尺寸在10-200nm的范围内,无机铜离子来自碱式硫酸铜、氧氯化铜、氢氧化铜之一种或多种,含铜有机物为乙酸铜、氨基酸铜、喹啉铜之一种或多种。
5.按照权利要求3所述具有含铜涂层的骨科植入器件,其特征在于:载铜微球中,基质材料与含铜物质的摩尔比在100:1-2:1的范围内。
6.按照权利要求1所述具有含铜涂层的骨科植入器件,其特征在于:所述聚合物为壳聚糖及其衍生物、聚氨酯、环糊精、淀粉、纤维素、海藻酸钠、胶原、聚乳酸、聚乙二醇、聚碳酸酯之一种或多种。
7.按照权利要求1所述具有含铜涂层的骨科植入器件,其特征在于:所述含铜聚合物涂层厚度小于等于5μm。
8.一种权利要求1所述骨科植入器件的制备方法,其特征在于,包括以下步骤:
步骤一:采用微乳液法制备载铜微球;
步骤二:制备不同配比的载铜微球聚合物溶液,通过浸提或喷涂法逐层制备具有载铜微球的聚合物涂层。
9.按照权利要求8所述骨科植入器件的制备方法,其特征在于,步骤一中采用微乳液法制备载铜微球包括以下步骤:
(1)配制质量体积浓度为5-150mg/mL的铜盐水溶液;
(2)配制质量体积浓度为5-900mg/mL的微球基质溶液,溶剂为体积比三氯甲烷:丙酮=1:4—4:1;
(3)配制质量体积浓度为1-200mg/mL的PVA水溶液;
(4)将铜盐水溶液加入微球基质溶液中,搅拌均匀后将混合液加入PVA水溶液中;
(5)采用机械搅拌或超声震荡的方法制备不同粒度的微球,其中,搅拌转数在500-5000rpm的范围内,搅拌时间为2-10h;超声功率在50-100W的范围内,超声时间为5-25min;
(6)利用离心或旋转蒸发的方法收集反应制得的微球,其中:
离心法所采取的转数为500-2000rpm,离心后去除上清液,将微球沉淀在蒸馏水中悬浮清洗,干燥;
旋转蒸发法所采取的转速为10-50rpm,将沉降一定时间的溶液,去上清液,将下层反应液加入旋转蒸发仪中,发生温度为30-45℃,时间为30min-2h。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810117480.8A CN108379658B (zh) | 2018-02-06 | 2018-02-06 | 具有含铜涂层的骨科植入器件及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810117480.8A CN108379658B (zh) | 2018-02-06 | 2018-02-06 | 具有含铜涂层的骨科植入器件及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108379658A CN108379658A (zh) | 2018-08-10 |
CN108379658B true CN108379658B (zh) | 2021-03-02 |
Family
ID=63075175
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810117480.8A Active CN108379658B (zh) | 2018-02-06 | 2018-02-06 | 具有含铜涂层的骨科植入器件及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108379658B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109338265B (zh) * | 2018-11-07 | 2020-10-16 | 江苏美霖铜业有限公司 | 一种Cu-Au复合镀层钛合金骨板及其生产方法 |
CN112121234A (zh) * | 2020-08-21 | 2020-12-25 | 中国科学院金属研究所 | 一种具有可控、持久抗感染骨科内植入物及其制备方法 |
CN113171224B (zh) * | 2021-04-08 | 2022-06-28 | 浙江大学 | 一种促进骨损伤修复的植入绷带及制备方法 |
CN114369808B (zh) * | 2021-12-20 | 2024-02-06 | 中国兵器科学研究院宁波分院 | 一种镁及镁合金表面制备抗菌涂层的方法 |
CN115212354A (zh) * | 2022-01-13 | 2022-10-21 | 南京航空航天大学 | 一种具有梯度涂层的骨修复支架及其制备方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3454513A (en) * | 1965-07-30 | 1969-07-08 | Martin V Azarian | Metal powders coated with silica and a water soluble acetate |
CN1631951A (zh) * | 2004-12-02 | 2005-06-29 | 同济大学 | 一种聚合物中空微球及其制备方法 |
CN101161300A (zh) * | 2007-11-27 | 2008-04-16 | 北京美中双和医疗器械有限公司 | 三氧化二砷药物洗脱支架 |
CN101791437A (zh) * | 2010-03-16 | 2010-08-04 | 浙江大学 | 一种聚合物/无机粒子复合骨修复多孔支架的制备方法 |
CN103751858A (zh) * | 2014-01-07 | 2014-04-30 | 东南大学 | 能促进血管再生的可吸收骨科器械材料及其制备方法 |
CN104127916A (zh) * | 2014-07-15 | 2014-11-05 | 东南大学 | 具有抗菌和促进骨生长功能可吸收骨科器械材料及制备方法 |
CN104673096A (zh) * | 2014-08-12 | 2015-06-03 | 西南交通大学 | 一种具有一氧化氮(no)催化活性的涂层的制备方法 |
-
2018
- 2018-02-06 CN CN201810117480.8A patent/CN108379658B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3454513A (en) * | 1965-07-30 | 1969-07-08 | Martin V Azarian | Metal powders coated with silica and a water soluble acetate |
CN1631951A (zh) * | 2004-12-02 | 2005-06-29 | 同济大学 | 一种聚合物中空微球及其制备方法 |
CN101161300A (zh) * | 2007-11-27 | 2008-04-16 | 北京美中双和医疗器械有限公司 | 三氧化二砷药物洗脱支架 |
CN101791437A (zh) * | 2010-03-16 | 2010-08-04 | 浙江大学 | 一种聚合物/无机粒子复合骨修复多孔支架的制备方法 |
CN103751858A (zh) * | 2014-01-07 | 2014-04-30 | 东南大学 | 能促进血管再生的可吸收骨科器械材料及其制备方法 |
CN104127916A (zh) * | 2014-07-15 | 2014-11-05 | 东南大学 | 具有抗菌和促进骨生长功能可吸收骨科器械材料及制备方法 |
CN104673096A (zh) * | 2014-08-12 | 2015-06-03 | 西南交通大学 | 一种具有一氧化氮(no)催化活性的涂层的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN108379658A (zh) | 2018-08-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108379658B (zh) | 具有含铜涂层的骨科植入器件及其制备方法 | |
CN111973811B (zh) | 一种含锌人工骨及其制备方法 | |
Eldeeb et al. | Biomaterials for tissue engineering applications and current updates in the field: a comprehensive review | |
CN108478843B (zh) | 具有含铜涂层的医用敷料及其制备方法 | |
Khor et al. | Implantable applications of chitin and chitosan | |
JP2003508128A (ja) | 生物活性物質及びその調製物を担持する新規多層型材料 | |
Xue et al. | In vitro and in vivo evaluation of chitosan scaffolds combined with simvastatin-loaded nanoparticles for guided bone regeneration | |
US20090010989A1 (en) | Coating For Implants and Implants With Improved Osteointegration, and Manufacturing Method | |
CN104195368A (zh) | 一种Zn-Sr系锌合金及其制备方法与应用 | |
CN101287505A (zh) | 用于植入物的涂层以及具有改进骨整合的植入物,和其制造方法 | |
WO2011065987A1 (en) | Granules of porous biocompatible materials | |
CN110234365A (zh) | 医学植入物和涂覆医学植入物的方法 | |
Hadisi et al. | In vitro and in vivo evaluation of silk fibroin-hardystonite-gentamicin nanofibrous scaffold for tissue engineering applications | |
Xu et al. | Noninvasive monitoring of bone regeneration using NaYF4: Yb3+, Er3+ upconversion hollow microtubes supporting PLGA-PEG-PLGA hydrogel | |
CN111317860A (zh) | 一种覆膜生物陶瓷人工骨及制备方法 | |
Yao et al. | Hollow hydroxyapatite microspheres/chitosan composite as a sustained delivery vehicle for rhBMP-2 in the treatment of bone defects | |
CN104519834B (zh) | 用于治疗骨空隙和开放性骨折的组合物和方法 | |
CN103705988B (zh) | 一种具有多功能涂层的髓内钉及其制备方法 | |
KR101277658B1 (ko) | 다중 약물전달계를 갖는 생체의료용 세라믹 재료의 제조 방법 | |
Ju et al. | Cyclic adenosine monophosphate-enhanced calvarial regeneration by bone marrow-derived mesenchymal stem cells on a hydroxyapatite/gelatin scaffold | |
CN108379669B (zh) | 具有含铜涂层的医用导管及其制备方法 | |
Zhou et al. | Novel coatings for the continuous repair of human bone defects | |
CN114558170A (zh) | 一种含生长因子颅骨修复聚醚醚酮材料及其制备方法 | |
Tavakoli et al. | 3D printed polylactic acid-based nanocomposite scaffold stuffed with microporous simvastatin-loaded polyelectrolyte for craniofacial reconstruction | |
Kim et al. | Osteogenic evaluation of calcium phosphate scaffold with drug-loaded poly (lactic-co-glycolic acid) microspheres in beagle dogs |
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 |