CN106924822A - 可吸收铁基合金内固定植入医疗器械 - Google Patents
可吸收铁基合金内固定植入医疗器械 Download PDFInfo
- Publication number
- CN106924822A CN106924822A CN201511032175.1A CN201511032175A CN106924822A CN 106924822 A CN106924822 A CN 106924822A CN 201511032175 A CN201511032175 A CN 201511032175A CN 106924822 A CN106924822 A CN 106924822A
- Authority
- CN
- China
- Prior art keywords
- degradable
- ferrous alloy
- medical device
- based alloy
- implanted medical
- 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.)
- Granted
Links
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 title claims abstract description 149
- 229910045601 alloy Inorganic materials 0.000 title claims abstract description 125
- 239000000956 alloy Substances 0.000 title claims abstract description 125
- 229910052742 iron Inorganic materials 0.000 title claims abstract description 69
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims abstract description 82
- 229920006237 degradable polymer Polymers 0.000 claims abstract description 30
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 20
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 19
- 239000011159 matrix material Substances 0.000 claims abstract description 12
- 150000008065 acid anhydrides Chemical class 0.000 claims description 24
- 229920001577 copolymer Polymers 0.000 claims description 24
- 229920000728 polyester Polymers 0.000 claims description 23
- 239000004626 polylactic acid Substances 0.000 claims description 22
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 21
- 235000006708 antioxidants Nutrition 0.000 claims description 18
- 239000003446 ligand Substances 0.000 claims description 17
- 239000004952 Polyamide Substances 0.000 claims description 15
- 229920002647 polyamide Polymers 0.000 claims description 15
- 239000008139 complexing agent Substances 0.000 claims description 14
- 239000000178 monomer Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- -1 alcohol ester Chemical class 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 229940024606 amino acid Drugs 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 229920000642 polymer Polymers 0.000 claims description 11
- 229920000388 Polyphosphate Polymers 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 239000001205 polyphosphate Substances 0.000 claims description 8
- 235000011176 polyphosphates Nutrition 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000010410 layer Substances 0.000 claims description 7
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 claims description 6
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 6
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 6
- 235000013824 polyphenols Nutrition 0.000 claims description 6
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims description 5
- 229920000858 Cyclodextrin Polymers 0.000 claims description 5
- 239000004831 Hot glue Substances 0.000 claims description 5
- 239000005062 Polybutadiene Substances 0.000 claims description 5
- 229920000954 Polyglycolide Polymers 0.000 claims description 5
- 229920000331 Polyhydroxybutyrate Polymers 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 5
- 150000008064 anhydrides Chemical class 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 claims description 5
- 239000005015 poly(hydroxybutyrate) Substances 0.000 claims description 5
- 229920002857 polybutadiene Polymers 0.000 claims description 5
- 239000004633 polyglycolic acid Substances 0.000 claims description 5
- 229920000903 polyhydroxyalkanoate Polymers 0.000 claims description 5
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 5
- 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 5
- 239000007787 solid Substances 0.000 claims description 5
- 229940070710 valerate Drugs 0.000 claims description 5
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 4
- 238000006731 degradation reaction Methods 0.000 claims description 4
- 108010064470 polyaspartate Proteins 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 4
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 4
- 229960005055 sodium ascorbate Drugs 0.000 claims description 4
- 235000019832 sodium triphosphate Nutrition 0.000 claims description 4
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 239000011719 vitamin A Substances 0.000 claims description 4
- 235000019155 vitamin A Nutrition 0.000 claims description 4
- 229940045997 vitamin a Drugs 0.000 claims description 4
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 108010024636 Glutathione Proteins 0.000 claims description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 3
- 235000021466 carotenoid Nutrition 0.000 claims description 3
- 150000001747 carotenoids Chemical class 0.000 claims description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 3
- 229960003180 glutathione Drugs 0.000 claims description 3
- 235000003969 glutathione Nutrition 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 229920005610 lignin Polymers 0.000 claims description 3
- 230000000598 lipoate effect Effects 0.000 claims description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 3
- 108010094020 polyglycine Proteins 0.000 claims description 3
- 229920000232 polyglycine polymer Polymers 0.000 claims description 3
- 239000013047 polymeric layer Substances 0.000 claims description 3
- 108010087948 polymethionine Proteins 0.000 claims description 3
- 229920001021 polysulfide Polymers 0.000 claims description 3
- 239000005077 polysulfide Substances 0.000 claims description 3
- 150000008117 polysulfides Polymers 0.000 claims description 3
- 235000010388 propyl gallate Nutrition 0.000 claims description 3
- 239000000473 propyl gallate Substances 0.000 claims description 3
- 229940075579 propyl gallate Drugs 0.000 claims description 3
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 3
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 3
- 235000010384 tocopherol Nutrition 0.000 claims description 3
- 229960001295 tocopherol Drugs 0.000 claims description 3
- 229930003799 tocopherol Natural products 0.000 claims description 3
- 239000011732 tocopherol Substances 0.000 claims description 3
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 3
- 239000004255 Butylated hydroxyanisole Substances 0.000 claims description 2
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 claims description 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 2
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 claims description 2
- 235000017471 coenzyme Q10 Nutrition 0.000 claims description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 claims description 2
- 238000009826 distribution Methods 0.000 claims description 2
- 230000001788 irregular Effects 0.000 claims description 2
- 239000004745 nonwoven fabric Substances 0.000 claims description 2
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 229940035936 ubiquinone Drugs 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000003205 fragrance Substances 0.000 claims 1
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims 1
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 claims 1
- 230000007797 corrosion Effects 0.000 abstract description 71
- 238000005260 corrosion Methods 0.000 abstract description 71
- 230000002708 enhancing effect Effects 0.000 abstract description 6
- 238000002513 implantation Methods 0.000 abstract description 5
- 239000000047 product Substances 0.000 description 55
- 229910000831 Steel Inorganic materials 0.000 description 23
- 239000010959 steel Substances 0.000 description 23
- 239000000463 material Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 9
- 235000001014 amino acid Nutrition 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- 229910000851 Alloy steel Inorganic materials 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229910000954 Medium-carbon steel Inorganic materials 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 238000005452 bending Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002464 physical blending Methods 0.000 description 4
- 238000004663 powder metallurgy Methods 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000003628 erosive effect Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000004698 iron complex Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 238000007493 shaping process Methods 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- YXAOOTNFFAQIPZ-UHFFFAOYSA-N 1-nitrosonaphthalen-2-ol Chemical compound C1=CC=CC2=C(N=O)C(O)=CC=C21 YXAOOTNFFAQIPZ-UHFFFAOYSA-N 0.000 description 2
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 240000006122 Chenopodium album Species 0.000 description 2
- 235000009344 Chenopodium album Nutrition 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 229910001209 Low-carbon steel Inorganic materials 0.000 description 2
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 2
- 235000014676 Phragmites communis Nutrition 0.000 description 2
- 229920000562 Poly(ethylene adipate) Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000005266 casting Methods 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- FZWBABZIGXEXES-UHFFFAOYSA-N ethane-1,2-diol;hexanedioic acid Chemical compound OCCO.OC(=O)CCCCC(O)=O FZWBABZIGXEXES-UHFFFAOYSA-N 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 239000000176 sodium gluconate Substances 0.000 description 2
- 235000012207 sodium gluconate Nutrition 0.000 description 2
- 229940005574 sodium gluconate Drugs 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical compound NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical group O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- RZCQYSSUIAJBDQ-UHFFFAOYSA-N 2-hydroxypropanoic acid;phosphoric acid Chemical compound OP(O)(O)=O.CC(O)C(O)=O RZCQYSSUIAJBDQ-UHFFFAOYSA-N 0.000 description 1
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 description 1
- HIOOFBBNJCVVJZ-UHFFFAOYSA-N 5-methyl-2-sulfanylbenzoic acid Chemical class CC1=CC=C(S)C(C(O)=O)=C1 HIOOFBBNJCVVJZ-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- 239000004114 Ammonium polyphosphate Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229940120146 EDTMP Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- TZXKOCQBRNJULO-UHFFFAOYSA-N Ferriprox Chemical class CC1=C(O)C(=O)C=CN1C TZXKOCQBRNJULO-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical group C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 235000019826 ammonium polyphosphate Nutrition 0.000 description 1
- 229920001276 ammonium polyphosphate Polymers 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical class OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 230000003280 chronobiological effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- FMSOAWSKCWYLBB-VBGLAJCLSA-N deferasirox Chemical compound C1=CC(C(=O)O)=CC=C1N(N\C(N\1)=C\2C(C=CC=C/2)=O)C/1=C\1C(=O)C=CC=C/1 FMSOAWSKCWYLBB-VBGLAJCLSA-N 0.000 description 1
- 229960001489 deferasirox Drugs 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- NFDRPXJGHKJRLJ-UHFFFAOYSA-N edtmp Chemical compound OP(O)(=O)CN(CP(O)(O)=O)CCN(CP(O)(O)=O)CP(O)(O)=O NFDRPXJGHKJRLJ-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- FLTRNWIFKITPIO-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe] FLTRNWIFKITPIO-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000009940 knitting Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- 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 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical group OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 238000013001 point bending Methods 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000010094 polymer processing Methods 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 239000001393 triammonium citrate Substances 0.000 description 1
- 235000011046 triammonium citrate Nutrition 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 229960001124 trientine Drugs 0.000 description 1
- 238000005829 trimerization reaction Methods 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000037314 wound repair 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
- A61L31/00—Materials 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
- A61L31/02—Inorganic materials
- A61L31/028—Other inorganic materials not covered by A61L31/022 - A61L31/026
-
- 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
- A61L31/00—Materials 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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
-
- 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
- A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
- A61L17/06—At least partially resorbable materials
- A61L17/10—At least partially resorbable materials containing 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
- A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
- A61L17/06—At least partially resorbable materials
- A61L17/10—At least partially resorbable materials containing macromolecular materials
- A61L17/12—Homopolymers or copolymers of glycolic acid or lactic acid
-
- 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
- A61L31/00—Materials 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
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
-
- 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
- A61L31/00—Materials 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
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L31/00—Materials 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
- A61L31/08—Materials for coatings
- A61L31/10—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
- A61L31/00—Materials 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
- A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
-
- 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
- A61L31/00—Materials 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
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L51/00—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
- C08L51/08—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers grafted on to macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
- C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
-
- 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
- A61L27/04—Metals or alloys
- A61L27/042—Iron or iron alloys
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Composite Materials (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明提供了一种可吸收铁基合金内固定植入医疗器械,其基体包括铁基合金和可降解聚合物,其特征在于,所述铁基合金与可降解聚合物的质量比在[1:4,4:1]之间,所述可降解聚合物的重均分子量在[15,300]万之间,多分散系数在[1,6]之间。本发明提供的可吸收铁基合金内固定植入医疗器械还包括抗氧化剂。本发明采用铁基合金作为器械的承重骨架或增强相,使器械在减少铁基合金基体用量的前提下具有良好的初始力学性能;通过调节铁基合金与可降解聚合物的质量比和组合方式,在加快铁基合金在植入后期的腐蚀速率的同时,减少了铁基合金难溶性腐蚀产物的量,减轻了组织对腐蚀产物代谢的负担;向器械中添加抗氧化剂进一步降低了铁基合金难溶性腐蚀产物的量。
Description
技术领域
本发明属于可吸收植入医疗器械领域,尤其涉及一种可吸收铁基合金内固定植入医疗器械。
背景技术
骨折愈合时间因受伤部位、受伤程度甚至治疗方法的不同而不同,通常为2~6个月,这要求内固定植入医疗器械具有一定的初始力学性能。例如通常骨钉的初始抗弯曲强度需达350MPa以上,缝线的抗拉强度需达400MPa以上。目前用于制造创伤修复用内固定植入医疗器械的材料主要有永久性金属如不锈钢、钛基合金、钴基合金,和可吸收材料如聚合物、镁基合金等。其中,永久性金属具有优异的力学性能和生物相容性,在受损骨愈合后将长期留在人体内,会存在潜在的长期生物学风险,若取出则会增加病人的痛苦和经济负担,同时有可能造成二次损伤(如滑牙折断残留体内)。
可吸收聚合物如聚乳酸、聚几内酯等具有良好的生物相容性已经积累了大量的临床数据。通常在一定范围内,聚合物的分子量和结晶度越高,其综合力学性能越好,但同时聚合物便越难溶于有机溶剂。因此只能通过将其加热为流动的熔融体后,再经模压、注塑、拉伸或挤出成型制成成品。对力学性能要求不高的结构,如医疗器械的可吸收聚合物涂层,通常是选用低分子量的聚合物并经有机溶剂溶解后,涂覆在医疗器械表面或内部。高分子量聚合物的加工方法通常是熔融后再加工成型,因此高分子量聚合物适用于制成具有一定力学强度的创伤修复用内固定植入医疗器械。
用高分子量聚乳酸制作的可吸收骨钉的抗弯强度虽可达150MPa以上,但与传统的永久性金属材料相比,存在以下缺点:力学性能差,通常仅适用于各种非承重部位的松质骨、关节骨或活动较少的骨的固定,以防过分受力或者活动频繁导致植入医疗器械的失效;聚乳酸降解会产生酸性环境,容易导致植入部位产生较严重的炎症反应;此外,显影性不好。这些缺点都制约了可吸收聚合物基内固定植入医疗器械的应用。
镁基合金内固定植入医疗器械的抗弯强度可达300MPa左右,但镁基合金的力学性能仍达不到永久性金属植入材料的水平,目前仍然只能用于非承重和活动较少的位置,例如对小骨和骨片的内固定,临床应用范围有限;此外,镁基合金腐蚀速率较快,植入医疗器械会过早丧失有效支撑和固定作用,且腐蚀时会使植入部位局部pH增高,对骨生长有不良影响,容易造成骨结合不好。
可吸收铁基合金的力学性能可接近永久性不锈钢、钴铬合金以及钛合金,相对可吸收聚合物和镁基合金具有更好的力学性能,但铁基合金的腐蚀速率缓慢。CN104587534公开了在可降解聚酯等高分子材料降解后形成的酸性微环境中,铁基合金的腐蚀速度可以显著提高,从而显著缩短铁基合金的腐蚀周期,但可吸收铁基合金通过吸氧腐蚀生成的腐蚀产物通常都是难溶的铁的氢氧化物或氧化物。在体内软硬组织中,这些难溶的铁的腐蚀产物被机体代谢和吸收的时间可能长达数年甚至更久,虽然它们的生物相容性很好,但是其长期存在加重了组织对其代谢的负担。因此,有必要在兼顾力学性能的同时,减少可吸收铁基合金内固定植入医疗器械的难溶性腐蚀产物。
发明内容
本发明提供了一种可吸收铁基合金内固定植入医疗器械,其在减少铁基合金基体用量的前提下具有较好的初始力学性能,且植入后期铁基合金难溶性腐蚀产物量较少,减轻了组织对其代谢的负担。
一种可吸收铁基合金内固定植入医疗器械,其基体包括铁基合金和可降解聚合物,所述铁基合金与所述可降解聚合物的质量比在[1:4,4:1]之间,所述可降解聚合物的重均分子量在[15,300]万之间,多分散系数在[1,6]之间。
所述铁基合金与所述可降解聚合物的质量比优选在[1:4,1:1]之间。
所述可吸收铁基合金内固定植入医疗器械中还包括抗氧化剂,所述抗氧化剂选自丁基羟基茴香醚、二丁基羟基甲苯、叔丁基对苯二酚、没食子酸丙酯、维生素A、类胡萝卜素、泛醌、谷胱甘肽、水溶性多酚、生育酚、三聚磷酸钠、抗坏血酸钠、硫辛酸盐、抗坏血酸棕榈酸酯中的至少一种,所述水溶性多酚选自白芦藜醇、黄酮类。
所述可降解聚合物包括可降解聚酯,或所述可降解聚酯与可降解聚酸酐、可降解聚氨基酸、可降解聚磷酸酯中的至少一种的混合物,或至少一种形成所述可降解聚酯的单体与至少一种形成所述可降解聚酸酐、可降解聚氨基酸或可降解聚磷酸酯的单体的共聚物。
所述可降解聚酯选自聚乳酸、聚乙醇酸、聚丁二酸酯、聚已内酯、聚羟基脂肪酸酯、聚己二酸乙二醇酯、聚乳酸-乙醇酸共聚物、聚羟基丁酸酯戊酸酯共聚物中的任意一种,或者选自聚乳酸、聚乙醇酸、聚丁二酸酯、聚已内酯、聚羟基脂肪酸酯、聚己二酸乙二醇酯、聚乳酸-乙醇酸共聚物、聚羟基丁酸酯戊酸酯共聚物中至少两种的物理共混物,或形成前述可降解聚酯的单体中的至少两种单体的共聚物;所述可降解聚酸酐选自交联聚酸酐、芳香族聚酸酐、脂肪族聚酸酐、杂环聚酸酐、聚酰酸酐、聚酰胺酸酐、含磷聚酸酐中的任意一种,或者选自交联聚酸酐、芳香族聚酸酐、脂肪族聚酸酐、杂环聚酸酐、聚酰酸酐、聚酰胺酸酐、含磷聚酸酐中至少两种的物理共混物;所述可降解聚氨基酸选自聚甘氨酸、聚蛋氨酸、聚硫代氨酸、聚天冬氨酸中的至少一种。
所述铁基合金为含碳质量百分比不高于2.11wt.%的纯铁或铁基合金。
所述可吸收铁基合金内固定植入医疗器械为骨钉或缝线。
相比现有技术,本发明采用铁基合金作为内固定植入医疗器械的承重骨架或增强相,使器械在减少铁基合金基体用量的前提下具有良好的初始力学性能;通过设置铁基合金与可降解聚合物的质量比和组合方式,在加快植入后期铁基合金基体腐蚀速率的同时,减少了铁基合金难溶性腐蚀产物的量,减轻了组织对腐蚀产物代谢的负担;添加抗氧化剂进一步降低了铁基合金难溶性腐蚀产物的量。
附图说明
图1为实施例1制备的骨钉的结构示意图。
图2为实施例2制备的骨钉的结构示意图。
图3为实施例5制备的用于制作骨钉的复合棒材的截面示意图。
具体实施方式
为了便于理解本发明,下面将参照相关附图对本发明进行更全面的描述。附图中给出了本发明的首选实施例。但是,本发明可以以许多不同的形式来实现,并不限于本文所描述的实施例。相反地,提供这些实施例的目的是使本发明的公开内容更加透彻全面。
除非另有定义,本文所使用的所有技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在说明书中所使用的术语只是为了描述具体的实施例的目的,不是旨在于限制本发明。
本发明的可吸收铁基合金内固定植入医疗器械的基体材料包括铁基合金和可降解聚合物,所述铁基合金与所述可降解聚合物的质量比在[1:4,4:1]之间,使得器械在减少铁基合金基体用量的前提下具有良好初始力学性能,在植入后期能够较快地腐蚀降解并减少了难溶性腐蚀产物的量,减轻了组织的代谢负担。
减少所述器械难溶性腐蚀产物的量的途径主要有两条:一是减少铁基合金基体的用量;二是减少铁基合金腐蚀产物中难溶性腐蚀产物的质量百分比,即提高铁基合金腐蚀产物中可溶性铁的质量百分比。
所述铁基合金和可降解聚合物复合材料的复合方式包括:
所述铁基合金以实心或中空须状、丝状、棒状、不规则支架或网状的形式分布在所述可降解聚合物中;或
所述铁基合金与所述可降解聚合物分别形成层状物且铁基合金层与聚合物层相互交替;或
所述铁基合金以丝状绞合在所述可降解聚合物丝上;或
所述铁基合金具有凹槽、孔隙、缝隙或中空内腔,所述可降解聚合物填充在所述凹槽、孔隙、缝隙或中空内腔中。
所述铁基合金和可降解聚合物采用上述复合方式,可以在获得接近或媲美永久性金属材料(如不锈钢、钴铬合金和钛基合金)器械的初始力学性能的同时减少铁基合金基体的用量,从而降低了可能生成的难溶性腐蚀产物的量。
所述可降解聚合物包括可降解聚酯,或所述可降解聚酯与可降解聚酸酐、可降解聚氨基酸、可降解聚磷酸酯中的至少一种的混合物,或至少一种形成所述可降解聚酯的单体与至少一种形成所述可降解聚酸酐、可降解聚氨基酸或可降解聚磷酸酯的单体的共聚物。
所述可降解聚酯选自聚乳酸、聚乙醇酸、聚丁二酸酯、聚已内酯、聚羟基脂肪酸酯、聚己二酸乙二醇酯、聚乳酸-乙醇酸共聚物、聚羟基丁酸酯戊酸酯共聚物中的任意一种,或者选自聚乳酸、聚乙醇酸、聚丁二酸酯、聚已内酯、聚羟基脂肪酸酯、聚己二酸乙二醇酯、聚乳酸-乙醇酸共聚物、聚羟基丁酸酯戊酸酯共聚物中至少两种的物理共混物,或形成前述可降解聚酯的单体中的至少两种单体的共聚物;所述可降解聚酸酐选自交联聚酸酐、芳香族聚酸酐、脂肪族聚酸酐、杂环聚酸酐、聚酰酸酐、聚酰胺酸酐、含磷聚酸酐中的任意一种,或者选自交联聚酸酐、芳香族聚酸酐、脂肪族聚酸酐、杂环聚酸酐、聚酰酸酐、聚酰胺酸酐、含磷聚酸酐中至少两种的物理共混物;所述可降解聚氨基酸选自聚甘氨酸、聚蛋氨酸、聚硫代氨酸、聚天冬氨酸中的至少一种。
可吸收铁基合金内固定植入医疗器械植入人体后,铁基合金基体在生理溶液中逐渐腐蚀生成初级腐蚀产物Fe3+或Fe2+,Fe3+或Fe2+随后与环境中的OH-反应,生成Fe(OH)2、Fe(OH)3等难溶性腐蚀产物。所述可降解聚酯、可降解聚酸酐、可降解聚氨基酸及可降解聚磷酸酯降解后释放出氢离子,可以有效抑制Fe3+或Fe2+与OH-的反应;此外,所述可降解聚酯、可降解聚酸酐、可降解聚氨基酸和可降解聚磷酸酯降解后生成的络离子(配体)较环境中的OH-优先与Fe3+或Fe2+配位反应生成稳定的可溶性铁络合物,从而能够进一步减少或者防止Fe3+或Fe2+与生理环境中的OH-反应生成难溶性腐蚀产物。所述器械中铁基合金与可降解聚合物的质量比越小,产生的离子或可溶性铁络合物形式的铁的量占铁基合金腐蚀产物中铁的质量比越高。但所述铁基合金与可降解聚合物的质量比越小,所述器械的力学性能便越差。因此,本发明铁基合金与可降解聚合物的质量比在[1:4,4:1]之间,优选在[1:4,1:1]之间,可以使所述器械能够在获得理想的力学性能的同时,减少难溶性腐蚀产物的量。
所述可吸收铁基合金内固定植入医疗器械中还包括抗氧化剂,所述抗氧化剂选自丁基羟基茴香醚、二丁基羟基甲苯、叔丁基对苯二酚、没食子酸丙酯、维生素A、类胡萝卜素、泛醌、谷胱甘肽、水溶性多酚、生育酚、三聚磷酸钠、抗坏血酸钠、硫辛酸盐、抗坏血酸棕榈酸酯中的至少一种,所述水溶性多酚选自白芦藜醇、黄酮类。
所述抗氧化剂可以涂覆在所述铁基合金表面;当铁基合金具有缝隙、凹槽或内腔时,所述抗氧化剂还可设于所述铁基合金的缝隙、凹槽、内腔中;此外,所述抗氧化剂可分散于所述可降解聚合物中。
尽管难溶性腐蚀产物在生理环境中的溶解度很小,但仍然存在少量离子进入溶液,同时进入溶液的离子又会在固体表面沉积下来,当难溶性腐蚀产物达到溶解平衡时,平衡常数称为溶度积常数(沉淀平衡常数),即溶度积。Fe3+和OH-生成的难溶性腐蚀产物Fe(OH)3的溶度积远远低于Fe2+和OH-生成的不溶腐蚀产物Fe(OH)2的溶度积,即进入溶液的Fe3+的量远低于进入溶液的Fe2+的量。因此三价铁的腐蚀产物在体内的代谢更加困难,向所述可吸收铁基合金内固定植入医疗器械中添加抗氧化剂,可以抑制Fe2+向Fe3+转化,从而能够减少难溶性三价铁腐蚀产物的生成,提高铁的溶解度。
所述可吸收铁基合金内固定植入医疗器械中还包括络合剂,所述络合体选自单齿配体和/或多齿配体。所述单齿配体含有单个配位基团,所述多齿配体含有至少两个配位基团,所述配位基团选自:稠环芳烃上的羟基、巯基(-SH)、胺基芳杂环基团、亚硝基(O=N-)、羰基磺基磷酸基团有机膦基团
所述稠环芳烃上的羟基选自酚羟基;所述芳杂环基团选自呋喃基吡咯基噻吩基咪唑基三唑基噻唑基吡啶基吡啶酮基吡喃基吡喃酮基嘧啶基哒嗪基吡嗪基喹啉基异喹啉基酞嗪基喋啶基吲哚基嘌呤基菲咯啉基
所述单齿配体选自葡萄糖酸、葡庚糖酸、乙醇酸,及其衍生物或盐类。
所述含稠环芳烃上的羟基的多齿配体选自8-羟基喹啉、8-羟基喹哪啶、4,5-二羟基苯-1,3-二磺酸钠、4-[3,5-二-羟苯基-1H-1,2,4-三唑]-苯甲酸(去铁斯若);所述含巯基的多齿配体选自8-巯基喹啉、巯基乙酸、5-甲基-2-巯基苯甲酸甲酯;所述含胺基的多齿配体选自乙二胺、三乙烯四胺、乙二胺四乙酸、乙二胺四乙酸四钠、N'-[5-[[4-[[5-(乙酰羟胺基)戊基]氨]-1,4-二氧丁基]羟胺]戊基]-N-(5-氨基戊基)-N-羟基琥珀酰胺(去铁胺);所述含芳杂环基团的多齿配体选自邻菲罗啉、联吡啶、卟啉、卟吩、叶绿素、血红蛋白、1,2-二甲基-3-羟基-4-吡啶酮(去铁酮);所述含亚硝基的多齿配体选自1-亚硝基-2-萘酚、1-亚硝基-2-萘酚-6-磺酸钠;所述含羰基的多齿配体选自多元羧酸及其盐、酸酐、酯、酰胺、聚羧酸、聚酸酐;所述含磺基的多齿配体选自磺基水杨酸、8-羟基喹啉-5-磺酸;所述含磷酸基团的多齿配体选自焦磷酸、三聚磷酸、六偏聚磷酸、多聚磷酸、焦磷酸钠、六偏聚磷酸钠、多聚磷酸铵;所述含有机膦基团的多齿配体选自二乙烯三胺五甲叉膦酸钾、乙二胺四甲叉膦酸钠,所述含羰基的多齿配体进一步选自草酸、酒石酸、苹果酸、琥珀酸、草酰乙酸、延胡索酸、马来酸、柠檬酸、柠檬酸三铵、氨三乙酸、二乙烯三胺五羧酸、海藻酸、谷氨酸、天冬氨酸、鸟氨酸、赖氨酸、柠檬酸钾、柠檬酸钙、柠檬酸甘油酯、乙酰水杨酸、磺基水杨酰胺、聚天冬氨酸、聚谷氨酸、聚鸟氨酸、聚赖氨酸、聚马来酸酐。
所述络合剂可以涂覆在所述铁基合金表面;当铁基合金具有缝隙、凹槽或内腔时,所述络合剂还可设于所述铁基合金的缝隙、凹槽、内腔中;此外,所述络合剂还可分散于所述可降解聚合物中。
在生理环境下,络合剂能提供孤对电子或π电子,与Fe2+和/或Fe3+发生络合反应,生成可水溶的铁络合物,水溶性铁络合物相比于铁基合金的难溶性固体腐蚀产物,能更快地被机体代谢/吸收。所述铁络合物的稳定性大于Fe(OH)2和/或Fe(OH)3,在生理溶液中不会转变成难溶的Fe(OH)2和/或Fe(OH)3。
所述可吸收铁基合金内固定植入医疗器械还包括生物相容性良好的可降解粘结剂,所述可降解粘结剂选自聚酯热熔胶、聚酰胺热熔胶、淀粉、环糊精、木质素中的至少一种,或选自由形成聚酯热熔胶、聚酰胺热熔胶、淀粉、环糊精、木质素的单体中的至少两种的共聚物。
为了考察可吸收铁基合金内固定植入医疗器械的腐蚀情况,本发明对器械进行体外加速腐蚀试验:在80℃条件下,将器械浸泡在100ml PBS溶液中腐蚀三周后,铁基合金腐蚀后生成的可溶性腐蚀产物充分溶解在PBS溶液中,用孔径为0.22μm的水性膜过滤浸泡液,然后采用原子吸收光谱仪(AAS)测试滤液中溶解的铁元素的浓度c,PBS溶液中溶解的可溶性铁的质量m1=cV,其中V为溶液体积;将器械取出,去除铁锈后洗净称重,计算得到铁基合金部分的失重为△m,即为铁基合金腐蚀产物中铁的质量;铁基合金腐蚀产物中可溶性铁的质量百分比W如公式(1)所示:
W=m1/△m×100% (1)
W—铁基合金腐蚀产物中可溶性铁腐蚀产物的质量百分比
m1—PBS溶液中的可溶性铁的质量
△m—铁基合金腐蚀产物中铁的质量
W越高,表明铁基合金腐蚀产物中形成的可溶性腐蚀产物越多,即难溶性腐蚀产物越少,组织代谢的负担越小。
本发明通过测试弯曲强度或抗拉强度对可吸收铁基合金内固定植入医疗器械的初始力学性能进行考察,本发明制备的内固定植入医疗器械初始抗弯曲强度不低于350MPa,抗拉强度不低于400MPa,视为达到用于承重部位的内固定植入医疗器械的标准。
本发明采用MTS公司生产的C43.504型号的万能材料试验机,根据YBT 5349-2006金属材料弯曲力学性能试验标准对试样的三点弯曲强度进行测试。
本发明采用MTS公司生产的C43.504型号的万能材料试验机,根据GBT 228.1-2010拉伸试验标准测试试样的抗拉强度。
需要指出的是,以下各实施例中,由于产品自身性能在设计许可范围内的正常波动以及测试方法不可避免引入的系统误差,实际检测到的铁基合金腐蚀产物中可溶性铁腐蚀产物的质量百分比会在一定范围内波动。
实施例1
将合金含量<6wt.%的低合金高强度钢铸造形成坯料,将坯料冷拔成直径为0.2mm的超细钢丝并进行热处理,将上述步骤制备的直径0.2mm的钢丝剪成长度不等的小段,然后在其上涂覆络合剂柠檬酸三铵。
将重均分子量为120万、多分散系数为1.1的聚乳酸乙醇酸(PLGA)坯料加热到熔融状态,PLGA坯料中分散有抗氧化剂维生素A;将上述处理后的钢丝段钢丝定向排列加入到熔融的PLGA坯料中作为增强相,冷凝固化后挤压成棒材,再机加工成如图1所示的骨钉10。其中钢丝增强相11与聚乳酸乙醇酸相12质量比为20:80。
本实施例制备的骨钉的材料初始弯曲强度为350MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为45wt.%。
实施例2
采用粉末冶金的方法将合金含量<6wt.%的低合金高强度钢制备成坯料,然后热轧成盘条,冷拔成空心钢丝,然后在空心钢丝芯部填充抗氧化剂抗坏血酸棕榈酸酯,将多股钢丝绞合成钢绞线并在其表面制备羟肟酸去铁胺络合剂层。
将重均分子量为300万、多分散系数为1.2的聚乳酸(PLA)和25万分子量的聚乳酸-蛋氨酸制成共混物坯料;将上述步骤制备的钢绞线置于所述熔融的聚乳酸(PLA)和聚乳酸-蛋氨酸的共混物坯料中作为增强相,固化后将其机加工成如图2所示的加压钉20,其中钢绞线增强相21与聚乳酸(PLA)和聚乳酸-蛋氨酸共混物相22的质量比为30:70。
本实施例制备的加压钉的材料初始弯曲强度为450MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为35wt.%。
实施例3
将合金含量<6wt.%的低合金高强度钢采用粉末冶金的方法获得坯料,然后热轧成盘条,冷拔成空心钢丝并在内填充络合剂乙酰水杨酸,将多股钢丝绞合后编织成二维网片,并在二维网片表面制备羟基磷灰石层再涂覆抗氧化剂泛醌。
将重均分子量为200万、多分散系数为1.5的聚乳酸坯料加热到熔融状态后将多层二维网片加入其中,混合均匀后冷凝固化并机加工成骨钉,骨钉中所有二维网片的延伸方向一致,且二维网片与聚乳酸坯料的质量比为25:75。
本实施例制备的骨钉的材料初始弯曲强度为400MPa,体外加速腐蚀三周后铁基合金可溶性腐蚀产物中可溶性铁的质量百分比为35wt.%。
实施例4
将铸态纯铁坯料热轧成盘条,冷拔成空心铁丝,在铁丝内腔中填充络合剂葡萄糖酸钠和抗氧化剂三聚磷酸钠;以熔融聚合方式得到的重均分子量为50万、多分散系数为5的乳酸-磷酸酯共聚物坯料并拉拔成丝,将共聚物和铁丝一起多股绞合形成丝径更大的绞线,向其中加入环糊精并紧压成型,制成可吸收缝线。缝线中铁丝与乳酸-磷酸酯共聚物的质量比为50:50。
本实施例制备的缝线的初始抗拉强度为400MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为25wt.%。
实施例5
将含碳量为0.3wt.%的中碳钢通过铸造获得坯料并进一步热处理;并将中碳钢与重均分子量为260万、多分散系数为2的分散有抗坏血酸钠的聚乳酸(PLA)坯料共同挤压制成横截面如图3所示的多层复合棒材,其中51为中碳钢层,52为聚合物层,向中碳钢层51和聚合物层52之间加入了聚酯热熔胶,再通过机械加工方式将棒材制成实心骨钉,其中,中碳钢和聚乳酸的质量比为50:50。
本实施例制备的骨钉的材料初始弯曲强度为450MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为15wt.%。
实施例6
将合金含量<6wt.%的低合金高强度钢通过铸造获得坯料,然后热轧成盘条,冷拔成空心钢丝,在钢丝内腔中填充络合剂葡萄糖酸钠;将重均分子量为300万、多分散系数为1.2的乳酸(PLA)-马来酸酐共聚物拉拔成丝,共聚物中还分散有抗氧化剂丁基羟基茴香醚;将所述钢丝和共聚物丝一起绞合成复合绞线,绞线制作过程中在钢丝和共聚物丝之间加入了聚酰胺热熔胶;最后将绞线机加工成加压钉,该加压钉中钢丝与共聚物丝的质量比为65:35。
本实施例制备的加压钉的初始弯曲强度为500MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为15wt.%。
实施例7
通过粉末冶金将含碳量为0.1wt.%的低碳低合金钢制成坯料并进一步热处理;将重均分子量为200万、多分散系数为1.8的聚乳酸和重均分子量为15万的聚马来酸酐-甘氨酸共聚物制成共混物;将低碳低合金钢坯料挤压成型后机加工成空心骨钉,并将聚乳酸与聚马来酸酐-蛋氨酸共聚物的共混物和抗氧化剂谷胱甘肽及络合剂六偏磷酸钠填充在骨钉内腔中,其中,低碳低合金钢与共混物的质量比为80:20。
本实施例制备的骨钉的材料初始弯曲强度为600MPa,体外加速腐蚀四周后铁基合金腐蚀产物中可溶性铁的质量百分比为10wt.%。
对比例1
将铸态的纯铁坯料热轧成盘条,冷拔成铁丝,将铁丝多股绞合制成缝线。
该缝合线的初始抗拉强度为600MPa。体外加速腐蚀四周后铁基合金腐蚀产物中可溶性铁的质量百分比为0。
对比例2
通过粉末冶金将含碳量为0.1wt.%的低碳低合金钢制成坯料并进一步热处理;将重均分子量为200万、多分散系数为1.8的聚乳酸和重均分子量为15万的聚马来酸酐-甘氨酸共聚物制成共混物;将低碳低合金钢坯料挤压成型后机加工成空心骨钉,并将聚乳酸与聚马来酸酐-蛋氨酸共聚物的共混物填充在骨钉内腔中,其中,低碳低合金钢与共混物的质量比为95:5。
该骨钉的材料初始弯曲强度为650MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为2wt.%。。
对比例3
将合金含量<6wt.%的低合金高强度钢铸造形成坯料,将坯料冷拔成直径为0.2mm的超细钢丝并进行热处理。
将重均分子量为10万、多分散系数为15的聚乳酸乙醇酸(PLGA)坯料加热到熔融状态;将上述步骤制备的直径0.2mm的钢丝剪成长度不等的小段并定向排列加入到熔融的PLGA坯料中作为增强相,冷凝固化后挤压成棒材,再机加工成如图1所示的骨钉10。其中钢丝增强相11与聚乳酸乙醇酸相12质量比为20:80。
该骨钉的材料初始弯曲强度为60MPa,体外加速腐蚀三周后铁基合金腐蚀产物中可溶性铁的质量百分比为10wt.%。
由实施例1~7和对比例1~3可以看出,各实施例制备的可吸收内固定植入医疗器械初始抗弯曲强度不低于350Mpa或抗拉强度不低于400MPa,均具有优良的初始力学性能,适用于承重部位的固定;通过设置铁基合金与可降解聚合物的质量比和组合方式,减少了铁基合金腐蚀产物中难溶性腐蚀产物的比例,抗氧化剂和络合剂的加入进一步降低了铁基合金腐蚀产物中难溶性腐蚀产物的比例,减轻了组织对腐蚀产物代谢的负担。
以上实施例仅表达了本发明的几种实施方式,其描述较为具体和详细,但并不能因此而理解为对本发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。因此,本发明专利的保护范围应以所附权利要求为准。
Claims (10)
1.一种可吸收铁基合金内固定植入医疗器械,其基体包括铁基合金和可降解聚合物,其特征在于,所述铁基合金与可降解聚合物的质量比在[1:4,4:1]之间,所述可降解聚合物的重均分子量在[15,300]万之间,多分散系数在[1,6]之间。
2.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述铁基合金与可降解聚合物的质量比在[1:4,1:1]之间。
3.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述器械还包括抗氧化剂,所述抗氧化剂选自丁基羟基茴香醚、二丁基羟基甲苯、叔丁基对苯二酚、没食子酸丙酯、维生素A、类胡萝卜素、泛醌、谷胱甘肽、水溶性多酚、生育酚、三聚磷酸钠、抗坏血酸钠、硫辛酸盐、抗坏血酸棕榈酸酯中的至少一种。
4.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述铁基合金与所述可降解聚合物的组合方式选自以下至少一种:所述铁基合金以实心或中空须状、丝状、棒状、不规则支架或网状的形式分布在所述可降解聚合物中;或
所述铁基合金与所述可降解聚合物分别形成层状物且铁基合金层与聚合物层相互交替;或
所述铁基合金以丝状绞合在所述可降解聚合物丝上;或
所述铁基合金具有凹槽、孔隙、缝隙或中空内腔,所述可降解聚合物填充在所述凹槽、孔隙、缝隙或中空内腔中。
5.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述可降解聚合物包括可降解聚酯,或所述可降解聚酯与可降解聚酸酐、可降解聚氨基酸、可降解聚磷酸酯中至少一种的混合物,或至少一种形成所述可降解聚酯的单体与至少一种形成所述可降解聚酸酐、可降解聚氨基酸或可降解聚磷酸酯的单体的共聚物。
6.根据权利要求5所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述可降解聚酯选自聚乳酸、聚乙醇酸、聚丁二酸酯、聚已内酯、聚羟基脂肪酸酯、聚己二酸乙二醇酯、聚乳酸-乙醇酸共聚物、聚羟基丁酸酯戊酸酯共聚物中的至少一种,或者选自形成前述可降解聚酯的单体中的至少两种单体的共聚物;所述可降解聚酸酐选自交联聚酸酐、芳香族聚酸酐、脂肪族聚酸酐、杂环聚酸酐、聚酰酸酐、聚酰胺酸酐、含磷聚酸酐中的至少一种;所述可降解聚氨基酸选自聚甘氨酸、聚蛋氨酸、聚硫代氨酸、聚天冬氨酸中的至少一种。
7.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述器械还包括络合剂,所述络合剂选自单齿配体和/或多齿配体,所述单齿配体含有单个配位基团,所述多齿配体含有至少两个配位基团,所述配位基团选自稠环芳烃上的羟基、巯基、胺基、芳杂环基团、亚硝基、羰基、磺基,磷酸基团或有机膦基团。
8.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述器械还包括粘结剂,所述可降解粘结剂选自聚酯热熔胶、聚酰胺热熔胶、淀粉、环糊精、木质素中的至少一种;或选自由形成聚酯热熔胶、聚酰胺热熔胶、淀粉、环糊精、木质素单体中的至少两种共聚物。
9.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述铁基合金为含碳质量百分比不高于2.11wt.%的纯铁或铁基合金。
10.根据权利要求1所述的可吸收铁基合金内固定植入医疗器械,其特征在于,所述器械为骨钉或缝线。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511032175.1A CN106924822B (zh) | 2015-12-31 | 2015-12-31 | 可吸收铁基合金内固定植入医疗器械 |
PCT/CN2016/087292 WO2017113657A1 (zh) | 2015-12-31 | 2016-06-27 | 可吸收铁基合金内固定植入医疗器械 |
US15/775,137 US11819591B2 (en) | 2015-12-31 | 2016-06-27 | Iron-based alloy absorbable and implantable medical device for internal fixation |
EP16880462.3A EP3398622B1 (en) | 2015-12-31 | 2016-06-27 | Iron-based alloy absorbable and implantable medical device for internal fixation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201511032175.1A CN106924822B (zh) | 2015-12-31 | 2015-12-31 | 可吸收铁基合金内固定植入医疗器械 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106924822A true CN106924822A (zh) | 2017-07-07 |
CN106924822B CN106924822B (zh) | 2020-02-28 |
Family
ID=59224339
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201511032175.1A Active CN106924822B (zh) | 2015-12-31 | 2015-12-31 | 可吸收铁基合金内固定植入医疗器械 |
Country Status (4)
Country | Link |
---|---|
US (1) | US11819591B2 (zh) |
EP (1) | EP3398622B1 (zh) |
CN (1) | CN106924822B (zh) |
WO (1) | WO2017113657A1 (zh) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108578787A (zh) * | 2018-08-07 | 2018-09-28 | 宁波宝亭生物科技有限公司 | 一种可吸收的骨固定装置及其制备方法 |
CN109954172A (zh) * | 2017-12-25 | 2019-07-02 | 先健科技(深圳)有限公司 | 可吸收铁基植入式器械 |
CN110731833A (zh) * | 2019-10-25 | 2020-01-31 | 郑州美港高科生物科技有限公司 | 铁基合金椎动脉可降解支架 |
WO2021135055A1 (zh) * | 2019-12-31 | 2021-07-08 | 元心科技(深圳)有限公司 | 可吸收金属器械 |
CN113116595A (zh) * | 2019-12-30 | 2021-07-16 | 元心科技(深圳)有限公司 | 可吸收铁基器械 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106902395B (zh) * | 2015-12-22 | 2020-04-07 | 先健科技(深圳)有限公司 | 可吸收铁基合金植入医疗器械 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100076556A1 (en) * | 2008-09-24 | 2010-03-25 | Intergran technologies, Inc. | In-vivo biodegradable medical implant |
US20110034996A1 (en) * | 2009-08-06 | 2011-02-10 | Alexander Borck | Medical implant containing an antioxidative substance |
US20110319978A1 (en) * | 2010-06-25 | 2011-12-29 | Fort Wayne Metals Research Products Corporation | Biodegradable composite wire for medical devices |
CN103877624A (zh) * | 2012-12-21 | 2014-06-25 | 上海微创医疗器械(集团)有限公司 | 一种可降解聚酯支架及其制备方法 |
CN104587534A (zh) * | 2013-10-31 | 2015-05-06 | 先健科技(深圳)有限公司 | 可吸收铁基合金支架 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2912923B2 (ja) * | 1995-09-25 | 1999-06-28 | タキロン株式会社 | 生体内分解吸収性の外科用材料及びその製造法 |
JP3141088B2 (ja) * | 1995-09-25 | 2001-03-05 | タキロン株式会社 | 生体内分解吸収性の外科用材料の製造法 |
US6306426B1 (en) * | 1997-08-11 | 2001-10-23 | Allergan Sales, Inc. | Implant device with a retinoid for improved biocompatibility |
AU2005308452A1 (en) * | 2004-11-26 | 2006-06-01 | Stentomics, Inc. | Chelating and binding chemicals to a medical implant |
US20060287676A1 (en) * | 2005-06-15 | 2006-12-21 | Rita Prajapati | Method of intra-operative coating therapeutic agents onto sutures, composite sutures and methods of use |
JP2009544411A (ja) * | 2006-07-26 | 2009-12-17 | ザ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 骨形成増進組成物 |
DE102008006455A1 (de) * | 2008-01-29 | 2009-07-30 | Biotronik Vi Patent Ag | Implantat mit einem Grundkörper aus einer biokorrodierbaren Legierung und einer korrosionshemmenden Beschichtung |
JP2009178293A (ja) * | 2008-01-30 | 2009-08-13 | Terumo Corp | 医療用インプラント |
US20110046721A1 (en) * | 2009-08-10 | 2011-02-24 | Surmodics, Inc. | Biodegradable Metal-Polymer Composite Constructs For Implantable Medical Devices |
CN102871715A (zh) * | 2012-10-30 | 2013-01-16 | 东南大学 | 高强度可吸收丝材复合骨内固定植入器械及其制备方法 |
CN103463686B (zh) * | 2013-09-09 | 2014-12-10 | 浙江大学 | 一种高强度医用壳聚糖接骨钉的制备方法 |
CN104720941A (zh) | 2013-12-20 | 2015-06-24 | 微创神通医疗科技(上海)有限公司 | 管道支架及其制备方法 |
-
2015
- 2015-12-31 CN CN201511032175.1A patent/CN106924822B/zh active Active
-
2016
- 2016-06-27 EP EP16880462.3A patent/EP3398622B1/en active Active
- 2016-06-27 US US15/775,137 patent/US11819591B2/en active Active
- 2016-06-27 WO PCT/CN2016/087292 patent/WO2017113657A1/zh active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100076556A1 (en) * | 2008-09-24 | 2010-03-25 | Intergran technologies, Inc. | In-vivo biodegradable medical implant |
US20110034996A1 (en) * | 2009-08-06 | 2011-02-10 | Alexander Borck | Medical implant containing an antioxidative substance |
US20110319978A1 (en) * | 2010-06-25 | 2011-12-29 | Fort Wayne Metals Research Products Corporation | Biodegradable composite wire for medical devices |
CN103877624A (zh) * | 2012-12-21 | 2014-06-25 | 上海微创医疗器械(集团)有限公司 | 一种可降解聚酯支架及其制备方法 |
CN104587534A (zh) * | 2013-10-31 | 2015-05-06 | 先健科技(深圳)有限公司 | 可吸收铁基合金支架 |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109954172A (zh) * | 2017-12-25 | 2019-07-02 | 先健科技(深圳)有限公司 | 可吸收铁基植入式器械 |
WO2019128453A1 (zh) * | 2017-12-25 | 2019-07-04 | 先健科技(深圳)有限公司 | 可吸收铁基植入式器械 |
CN108578787A (zh) * | 2018-08-07 | 2018-09-28 | 宁波宝亭生物科技有限公司 | 一种可吸收的骨固定装置及其制备方法 |
CN110731833A (zh) * | 2019-10-25 | 2020-01-31 | 郑州美港高科生物科技有限公司 | 铁基合金椎动脉可降解支架 |
CN113116595A (zh) * | 2019-12-30 | 2021-07-16 | 元心科技(深圳)有限公司 | 可吸收铁基器械 |
CN113116595B (zh) * | 2019-12-30 | 2022-06-21 | 元心科技(深圳)有限公司 | 可吸收铁基器械 |
WO2021135055A1 (zh) * | 2019-12-31 | 2021-07-08 | 元心科技(深圳)有限公司 | 可吸收金属器械 |
Also Published As
Publication number | Publication date |
---|---|
EP3398622B1 (en) | 2022-03-16 |
WO2017113657A1 (zh) | 2017-07-06 |
EP3398622A1 (en) | 2018-11-07 |
EP3398622A4 (en) | 2019-09-11 |
CN106924822B (zh) | 2020-02-28 |
US20180326127A1 (en) | 2018-11-15 |
US11819591B2 (en) | 2023-11-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106924822A (zh) | 可吸收铁基合金内固定植入医疗器械 | |
CN104587534A (zh) | 可吸收铁基合金支架 | |
CN104212998B (zh) | 一种Zn‑Mg系锌合金及其制备方法与应用 | |
DE112011103342T5 (de) | Stickstoffoxid-Abgabesysteme unter Verwendung von wärmeempfindlichen svnthetischen Polymeren | |
Varshosaz et al. | Poly (butylene adipate-co-terephthalate) electrospun nanofibers loaded with 5-fluorouracil and curcumin in treatment of colorectal cancer cells | |
CN104195368A (zh) | 一种Zn-Sr系锌合金及其制备方法与应用 | |
Sepahvandi et al. | Fabrication and characterization of SrAl2O4: Eu2+ Dy3+/CS-PCL electrospun nanocomposite scaffold for retinal tissue regeneration | |
CN106955374A (zh) | 植入式器械 | |
Weems et al. | Shape memory polymers with enhanced visibility for magnetic resonance-and X-ray imaging modalities | |
EP2272547A1 (de) | Implantat und Verfahren zur Herstellung desselben | |
EP2329853B1 (de) | Beschichtete Eisenbasislegierung für medizinische Implantate | |
DE10113659A1 (de) | Material für medizinische Stents und Einrichtung zum induktiven intrakorporalen Erwärmen dieser Stents | |
Doan et al. | Fluorescence conjugated nanostructured cobalt-doped hydroxyapatite platform for imaging-guided drug delivery application | |
EP2206526A2 (de) | Implantat und Verfahren zur Herstellung desselben | |
CN106902395B (zh) | 可吸收铁基合金植入医疗器械 | |
EP2701757B1 (de) | Implantierbare gefässstütze | |
CN109289094B (zh) | 一种血管支架材料及其制备方法 | |
CN109803693A (zh) | 医疗器械 | |
Guo et al. | Phase evolution, mechanical properties and MRI contrast behavior of GdPO4 doped hydroxyapatite for dental applications | |
Jamil et al. | Parameterisation and cellular evaluation of poly (ethylene) oxide-coated erbium oxide in MCF-7 cells as MRI diagnostic nanofibres | |
CN111514315A (zh) | 一种肿瘤靶向无定形磷酸钙荧光纳米复合材料负载药物的方法 | |
CN117225924A (zh) | 一种腐蚀速率可控的生物可降解tips支架及其制备方法 | |
DE102022121135A1 (de) | Verfahren zur Herstellung von Gefäßimplantaten mit einer magnetisierten Oberfläche | |
Malafeev et al. | Studies of the in vivo bioresorption rate of composite filaments on the basis of polylactide filled with chitin nanofibrils or silver nanoparticles. | |
EP4036136A1 (de) | Verfahren zur herstellung von gefässprothesen |
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: 20210205 Address after: 518000 4th floor, building 4, Jinxiu Science Park, Wuhe Avenue, Longhua District, Shenzhen City, Guangdong Province Patentee after: Yuanxin Science and Technology (Shenzhen) Co.,Ltd. Address before: 518000 1st-5th Floor of Saiba Research Building, Langshan Second Road, North District of Nanshan High-tech Industrial Park, Shenzhen City, Guangdong Province Patentee before: Lifetech Scientific (Shenzhen) Co.,Ltd. |