CN1298395C - 一种钙磷盐基骨修复材料及其制备方法 - Google Patents
一种钙磷盐基骨修复材料及其制备方法 Download PDFInfo
- Publication number
- CN1298395C CN1298395C CNB2004100341093A CN200410034109A CN1298395C CN 1298395 C CN1298395 C CN 1298395C CN B2004100341093 A CNB2004100341093 A CN B2004100341093A CN 200410034109 A CN200410034109 A CN 200410034109A CN 1298395 C CN1298395 C CN 1298395C
- Authority
- CN
- China
- Prior art keywords
- calcium
- chitin
- fiber
- chitosan
- bone
- 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.)
- Expired - Fee Related
Links
- 239000000463 material Substances 0.000 title claims abstract description 41
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 36
- 239000011575 calcium Substances 0.000 title claims description 46
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims description 30
- 229910052791 calcium Inorganic materials 0.000 title claims description 30
- 238000002360 preparation method Methods 0.000 title claims description 14
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title 1
- 239000000835 fiber Substances 0.000 claims abstract description 104
- 229920002101 Chitin Polymers 0.000 claims abstract description 69
- 229920001661 Chitosan Polymers 0.000 claims abstract description 61
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 claims abstract description 16
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 claims abstract description 16
- 229940112869 bone morphogenetic protein Drugs 0.000 claims abstract description 16
- 102000008186 Collagen Human genes 0.000 claims abstract description 13
- 108010035532 Collagen Proteins 0.000 claims abstract description 13
- 229920001436 collagen Polymers 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 8
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims abstract description 7
- 229960000485 methotrexate Drugs 0.000 claims abstract description 7
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 27
- CUXQLKLUPGTTKL-UHFFFAOYSA-M microcosmic salt Chemical compound [NH4+].[Na+].OP([O-])([O-])=O CUXQLKLUPGTTKL-UHFFFAOYSA-M 0.000 claims description 27
- 239000001506 calcium phosphate Substances 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 26
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 21
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 21
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 20
- 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 20
- 239000000203 mixture Substances 0.000 claims description 19
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 claims description 18
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 16
- 235000011010 calcium phosphates Nutrition 0.000 claims description 16
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical class CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims description 15
- 229920001577 copolymer Polymers 0.000 claims description 15
- 239000002002 slurry Substances 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 11
- 230000026731 phosphorylation Effects 0.000 claims description 11
- 238000006366 phosphorylation reaction Methods 0.000 claims description 11
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 10
- 239000004310 lactic acid Substances 0.000 claims description 10
- 235000014655 lactic acid Nutrition 0.000 claims description 10
- 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 10
- 230000019635 sulfation Effects 0.000 claims description 10
- 238000005670 sulfation reaction Methods 0.000 claims description 10
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 8
- -1 biphosphate calcium compound Chemical class 0.000 claims description 7
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 claims description 6
- 229930195573 Amycin Natural products 0.000 claims description 6
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 6
- 239000004626 polylactic acid Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 241001597008 Nomeidae Species 0.000 claims description 4
- 239000004698 Polyethylene Substances 0.000 claims description 4
- 229920000573 polyethylene Polymers 0.000 claims description 4
- 229920006306 polyurethane fiber Polymers 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 2
- 229940043430 calcium compound Drugs 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000292 calcium oxide Substances 0.000 claims description 2
- 235000019691 monocalcium phosphate Nutrition 0.000 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 2
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical class CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 5
- 238000001727 in vivo Methods 0.000 abstract description 5
- 210000001519 tissue Anatomy 0.000 abstract description 5
- 230000007547 defect Effects 0.000 abstract description 4
- 241001465754 Metazoa Species 0.000 abstract description 2
- 208000001132 Osteoporosis Diseases 0.000 abstract description 2
- 210000000845 cartilage Anatomy 0.000 abstract description 2
- 230000011164 ossification Effects 0.000 abstract description 2
- 210000000515 tooth Anatomy 0.000 abstract description 2
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 abstract 3
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 abstract 2
- 208000018084 Bone neoplasm Diseases 0.000 abstract 1
- 229940009456 adriamycin Drugs 0.000 abstract 1
- 229960005188 collagen Drugs 0.000 abstract 1
- 230000004821 effect on bone Effects 0.000 abstract 1
- 230000002349 favourable effect Effects 0.000 abstract 1
- 229960001714 calcium phosphate Drugs 0.000 description 22
- 239000002639 bone cement Substances 0.000 description 18
- 229960005069 calcium Drugs 0.000 description 17
- HECLRDQVFMWTQS-UHFFFAOYSA-N Dicyclopentadiene Chemical compound C1C2C3CC=CC3C1C=C2 HECLRDQVFMWTQS-UHFFFAOYSA-N 0.000 description 11
- 239000007788 liquid Substances 0.000 description 10
- 239000012620 biological material Substances 0.000 description 9
- 239000004568 cement Substances 0.000 description 9
- 230000006196 deacetylation Effects 0.000 description 8
- 238000003381 deacetylation reaction Methods 0.000 description 8
- 238000006467 substitution reaction Methods 0.000 description 8
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 6
- LFULEKSKNZEWOE-UHFFFAOYSA-N propanil Chemical compound CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 LFULEKSKNZEWOE-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 229920001020 poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) Polymers 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000002787 reinforcement Effects 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 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 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- ZOMBKNNSYQHRCA-UHFFFAOYSA-J calcium sulfate hemihydrate Chemical compound O.[Ca+2].[Ca+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O ZOMBKNNSYQHRCA-UHFFFAOYSA-J 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 239000004570 mortar (masonry) Substances 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000012064 sodium phosphate buffer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 229920000018 Callose Polymers 0.000 description 1
- 229920000049 Carbon (fiber) Polymers 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 241000371997 Eriocheir sinensis Species 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- BUKPYVZUSQQGJS-UHFFFAOYSA-L [Ca+2].O.[PH2](=O)[O-].[PH2](=O)[O-] Chemical compound [Ca+2].O.[PH2](=O)[O-].[PH2](=O)[O-] BUKPYVZUSQQGJS-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000003462 bioceramic Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229940095643 calcium hydroxide Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004917 carbon fiber Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000002414 leg Anatomy 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 238000009941 weaving Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
Abstract
一种钙磷盐基骨修复材料及其制备方法，涉及一种生物组织材料及其制备。本发明所述的材料含有钙磷盐和甲壳素/壳聚糖纤维，所述甲壳素/壳聚糖纤维以纤维丝或纤维束形式存在。在该材料中还可复合0.1～10%的甲壳素衍生物如壳聚糖、磷酸化甲壳素、磷酸化壳聚糖、羧基化硫酸酯化壳聚糖、和/或0.01～0.1%胶原、骨形成蛋白、甲氨蝶呤或阿霉素。细胞实验和动物实验都表明：材料具有良好的生物相容性和诱导成骨活性，对于钙磷盐基骨修复材料，可使其抗挠(弯)强度平均提高1～10倍，是一种可靠的体内可降解的组织修复及治疗材料，对于骨缺损、骨质疏松、骨肿瘤治疗效果明显；在生物组织(如骨、软骨、牙)修复中具有广泛的应用价值。
Description
技术领域
本发明涉及一种生物组织修复材料，特别涉及一种骨修复材料及其制备方法。
背景技术
甲壳素(Chitin)又名甲壳质、几丁质、壳多糖、壳蛋白等，是一种维持和保护甲壳动物及微生物躯体的不溶于水、碱和常规溶剂的线性氨基多糖，广泛存在于节足动物类(蜘蛛类、甲壳类)的翅膀或外壳以及菌类和藻类的细胞壁中，每年生物合成近十亿吨之多，仅在蟹、虾等水产品加工后的甲壳废弃物中就有10～30％的含量，是一种具有潜在价值、尚待开发的自然资源。酸溶性壳聚糖(Chitosan)是甲壳素的脱乙酰化合物，属甲壳素的衍生物，分子量为12～59万，化学名为聚(1，4)-2-氨基-2-脱氧-β-D-葡聚糖，具有明显的碱性、良好的生物相容性和生物可降解性，降解产物为对人体无毒的N-乙酰氨基葡萄糖和氨基葡萄糖，降解过程中产生的中间产物在体内不积累，无免疫源性(姜雪松，王勃生等.生物医学工程学杂志，1996；13(4)：353.)。近年来，随着研究的深入和广泛，甲壳素衍生物的应用已涉及到纺织、印染、造纸、医疗及水处理等许多部门或领域。尤其是作为具有独特性能的生物材料，越来越引起人们的注意，有些项目已具有生产价值和实用意义。
组织修复，尤其是大段骨缺损的修复一直是困扰外科医生的一个棘手问题。过去的几十年中，尽管制备了许多种骨替代材料，但临床上70％的骨替代材料仍然使用自体骨或异体骨，使病人面临高的手术综合症和感染率。因为人们对现有的骨修复材料还缺乏信心，尤其是涉及到长期的体内安全性和效果的问题(Langstaff S，Sayer M，Smith TJN，Pugh SM.Resorbable bioceramics based on stabilized calcium phosphates.Part II：evalu tion ofbiological response.Biomaterials，2001；22：135.)，使合成材料的使用受到了限制。到目前为止既能满足一定的机械强度、一定韧性要求的，又具备良好生物相容性的大段骨修复材料还绝无仅有。
磷酸钙骨水泥作为一类有发展潜力的生物材料，由于其高的骨传导性、易与骨结合、容易塑型(或注射)及逐渐降解等特点，越来越引起重视。目前，国内外文献中报道的15种以上骨水泥，大部分以羟基磷灰石(HA)作为其唯一的或主要的终产物。磷酸四钙与无水(或二水合)磷酸氢钙，氧化锌与磷酸，单水合磷酸二氢钙、α-磷酸钙与碳酸钙，β-磷酸钙、磷酸二氢钙与半水合硫酸钙等均为较常用的骨水泥系。羟基磷灰石是硬组织(如骨、牙)中无机盐的主要成分，与自然骨相比，有机质的缺乏是导致骨水泥早期与血液接触时溃散、植入体内后容易疲劳的主要原因(Hong YC，Wang JT，Brown WE，Chow LC.The periapical tissuereactions to a calcium phosphate cement in the teeth of monkeys.J Biomed MaterRes，1991；25：485)。
为了改善骨水泥的性能，多种有机添加剂被引用到骨水泥中，如海藻酸钠(Ishikawa K，Miyamoto Y，Kon M，Nagayama M，Asaoka K.Non-decay type fast-setting calciumphosphate cement：composite with sodium alginate.Biomaterials，1995；16：527.)、(氢)脯氨酰基甲基纤维素和羧甲基纤维素(Cherng A，Takagi S，Chow LC.Effects ofhydroxypropyl methylcellulose and other gelling agents on the handling propertiesof calcium phosphate cement.J Biomed Mater Res，1997；35：273.)曾被用来增强磷酸四钙(TTCP)骨水泥的粘合力，但骨水泥的硬化时间可能被延长，或机械强度下降，或有机物在体内很难被降解，几乎所有的有机物对骨水泥的性能都会产生副作用。本作者曾将磷酸化甲壳素和磷酸化壳聚糖等甲壳素衍生物应用于磷酸钙基骨修复材料，发现磷酸化甲壳素、磷酸化壳聚糖、羧基化硫酸酯化壳聚糖可增强骨水泥的机械强度(
Wang XH，Ma J，WangY，He B.Structural characterization of phosphorylated chitosan and theirapplications as effective additives of calcium phosphate cements.Biomaterials，2001；22：2247-2255；
Wang XH，Ma J，Wang Y，He B.Reinforcement of calcium phosphatecements with phosphorylated chitin.Chinese Journal of Polymer Science，2002；20：325-332；
Wang XH，Ma J，Wang Y，He B.Bone repair in radii and tibias ofrabbits with phosphorylated chitosan reinforced calcium phosphate cements.Biomaterials，2002；23：4167-4176；
Wang XH，Ma J，Feng QL，Cui FZ.Skeletal repairin of rabbits with calcium phosphate cements incorporated phosphorylated chitinreinforced.Biomaterials，2002；23：4591-4600；
Wang XH，Ma J，Feng QL，Cui FZ.“Theeffects of S-chitosan on the physical properties of calcium phosphate cements”.Journal of Bioactive and Compatible polymers，2003；18：45-57；
Wang XH，Ma J，FengQL，Cui FZ.In vivo testing of S-chitosan enhanced calcium phosphate cements.Journal of Bioactive and Compatible polymers，2003；18：259-271)，但骨水泥的韧性增强很少，甲壳素衍生物增强后的骨水泥仍然为脆性材料。近年来，一些丝状或网状不可被生物降解的纤维如聚丙烯、尼龙、碳纤维[yon Gonten AS.Kelly JR，AntonucciJM.Load-bearing behavior of a simulated craniofacial structure fabricated from ahydroxyapatite cement and bioresorbable fiber-mesh.J Mater Sci：Mater Med2000；11：95-100；dos Santos LA，Carrodéguas，Boschi AO，de Arruda ACF.Fiber-enricheddouble-setting calcium phosphate bone cement.J Biomed Mater Res 65A：244-250]以及可被水解纤维如乙烯醇与乳酸的共聚物VicrylTM(polyglactin 910，Ethicon，Somerville，NJ)及Vicryl RapideTM(polyglactin 910，Ethicon)[Xu HHK，Quinn JB.Calcium phosphatecement containing resorbable fibers for short-term reinforcement and macroporosity.Biomaterials 2002；23：193-202](Xu HHK，Quinn JB，Takagi S，Chow LC.Synergisticreinforcement of in situ hardening calcium phosphate composite scaffold for bonetissue engineering.Biomaterials 2004；25：1029-1037)曾用来增强磷酸四钙骨水泥的韧性。这些纤维有的不能被生物降解，有的价格昂贵，有的生物相容性很差。目前还没有用甲壳素/壳聚糖纤维来增强骨修复材料，尤其是大段骨修复材料的报道。
发明内容
本发明的目的是提供一种韧性较强的，生物相容性较好的，价格较便宜的骨修复材料。
一种钙磷盐基骨修复材料，其特征在于：该材料含有钙磷盐、甲壳素/壳聚糖纤维，所述的甲壳素/壳聚糖纤维占钙磷盐总重量的0.1～5％，所述甲壳素/壳聚糖纤维以纤维丝或纤维束形式存在。
本发明所述材料还含有钙磷盐总重量0.1～10％的甲壳素衍生物，所述的衍生物为壳聚糖、磷酸化甲壳素、磷酸化壳聚糖、羧基化硫酸酯化壳聚。
在上述方案的基础上，本发明所述材料还含有占钙磷盐总重量的0.01～0.1％的胶原、骨形成蛋白、甲氨蝶呤或阿霉素。
本发明所述的纤维丝为3～10mm长的短纤维丝，所述的纤维束为直径50～500μm，长度为2～30cm的纤维束。
本发明所述的钙磷盐采用由氧化钙和磷酸二氢钙混合物，氢氧化钙和磷酸氢钙混合物，磷酸四钙与磷酸氢钙混合物，α-磷酸钙、磷酸二氢钙和碳酸钙混合物，α-磷酸钙、磷酸氢钙、碳酸钙、磷酸四钙混合物制备而成；或直接采用羟基磷灰石、磷酸钙。
本发明的技术特征还在于：所述的甲壳素/壳聚糖纤维束还可与可降解的聚乙烯醇纤维、乳酸与乙醇酸的共聚物纤维、胶原纤维、聚乙烯醇纤维、聚3-羟基丁酸盐纤维、3-羟基丁酸和3-羟基己酸共聚物纤维或聚氨酯纤维按1～20∶20～1比例混合编制成网格状、梯形状结构。
本发明还提供了一种钙磷盐基骨修复材料的制备方法，该方法按如下步骤进行：
a.首先将钙磷盐粉末与磷酸钠缓冲溶液混合制成浆状物，或将钙磷盐粉末与聚乳酸、乳酸与乙醇酸的共聚物的氯仿或1，4二氧六环溶液混合制成浆状物；
b.将甲壳素/壳聚糖纤维剪制成3～10mm长的短纤维丝，或编成直径为50～500μm，长度为2～30cm纤维束与步骤a中的浆状物复合；其中甲壳素/壳聚糖纤维占钙磷盐总重量的0.1～5％；
c.然后经自然凉干或将溶剂除去后形成含纤维的固态物质。
在所述的步骤a中还可加入占钙磷盐总重量0.1～10％的甲壳素衍生物，所述的衍生物为壳聚糖、磷酸化甲壳素、磷酸化壳聚糖、羧基化硫酸酯化壳聚。
在所述的方法中，步骤a中还可加入占钙磷盐总重量的0.01～0.1％的骨形成蛋白、甲氨蝶呤或阿霉素。
上述步骤b中的纤维束还可与可降解的聚乙烯醇纤维、乳酸与乙醇酸的共聚物纤维、胶原纤维、聚乙烯醇纤维、聚3-羟基丁酸盐纤维、3-羟基丁酸和3-羟基己酸共聚物纤维或聚氨酯纤维按1～20∶20～1比例混合编制成网格状、梯形状结构后再与浆状物复合。
本发明利用甲壳素/壳聚糖纤维增强钙磷盐基骨修复材料。对于钙磷盐基骨修复材料，可使其抗挠(弯)强度平均提高1～10倍，是一种可靠的体内可降解的组织修复及治疗材料，对于骨缺损、骨质疏松、骨肿瘤治疗效果明显；在生物组织(如骨、软骨、牙)修复中具有广泛的应用价值。
具体实施方式
所述甲壳素衍生物可以是磷酸化甲壳素，磷酸化甲壳素的羟基取代度为0.05～0.99，分子量为5000～10000道尔顿；也可以是磷酸化壳聚糖，磷酸化壳聚糖的脱乙酰度为5～95％，羟基取代度为0.02～0.95，分子量为5000～10000道尔顿；还可以是羧丁基壳聚糖，羧丁基壳聚糖的脱乙酰度为10～90％，羟基取代度为0.05～0.95，分子量为2×104～6×106道尔顿；对于骨瘤和白血病患者，又可以是甲氨蝶呤、阿霉素或羧基化硫酸酯化壳聚糖，羧基化硫酸酯化壳聚糖的脱乙酰度为15～95％，羟基取代度为0.01～0.75，分子量为5000～10000道尔顿。
本发明的磷酸化甲壳素、磷酸化壳聚糖可按照文献Nishi N，Ebina A，Nishimura S，Tsutsumi A，Hasegawa O，Tokura S.Highly phosphorylated derivatives of chitin，partially deacetylated chitin and chitosan as new functional polymers：preparationand characterization.Int J Biol Macromol 1986；8：311-317所述的方法制备。羧丁基壳聚糖可按文献Muzzarelli R，Weckx M，Filippini O，Lough C.Characteristic Propertiesof N-Carboxybutyl Chitosan.Carbohydrate Polymers 1989；II：307-320所述的方法制备。羧基化硫酸酯化壳聚糖可按文献Horton D，Just EK.Preparation from chitin of(1→4)-2-amino-2-deoxy-β-D-glucopyranuronan and its 2-sulfoamino analog havingblood-anticoagulant properties.Carbohydr Res 1973；29：173-179所述的方法制备。碳酸氢钠(NaHCO3)、氧化钙(CaO)、磷酸二氢钙(MCPM)、氢氧化钙[Ca(OH)2]和磷酸氢钙(DCPDor DCPA)等由北京化学试剂公司购买。甲壳素/壳聚糖纤维由青岛弘信高科技生物工程有限公司购买(其中壳聚糖的脱乙酰度在80以上)。其中甲壳素/壳聚糖纤维又称甲壳质纤维也可从上海浦东甲壳质材料研究&开发有限责任公司等处购买。骨形成蛋白(rhBMP-2)、甲氨蝶呤、阿霉素、胶原、聚乙烯醇纤维或乙烯醇与乳酸的共聚物VicrylTM及Vicryl RapideTM由Ethicon，Somerville，NJ等公司购买。聚乳酸(PLLA)、乙醇酸与乳酸的共聚物(PLGA)由山东医用公司购买。
下面结合具体实施例对本发明做进一步说明。
实施例1：
将研磨后的氧化钙(CaO)和磷酸二氢钙(MCPM)粉末按下列方程(1)比例混合。将甲壳素纤维剪成3mm长的短纤维，按重量比0.1％混合在粉末中。在1mL 1M的磷酸缓冲液(由NaH2PO4和Na2HPO4·12H2O制备)中加入分别占氧化钙(CaO)和磷酸二氢钙(MCPM)粉末总重量0.1％的磷酸化甲壳素和0.01％的骨形成蛋白rhBMP-2，搅拌均匀后，与含甲壳素纤维的固体粉末混合均匀，固液比是0.96。
实施例2：
将研磨后的Ca(OH)2和磷酸氢钙(DCPD)粉末按下列方程(2)比例混合。将甲壳素纤维剪成6mm长的短纤维，按重量比5％混合在粉末中。在1mL 1M的Na2HPO4水溶液中加入分别占Ca(OH)2和磷酸氢钙(DCPD)粉末总重量1％的磷酸化壳聚糖和0.05％的骨形成蛋自rhBMP-2，搅拌均匀后与甲壳质纤维的固体粉末在研钵中仔细研磨，固液比是2.29。
实施例3：
将等摩尔的磷酸四钙(TTCP)与磷酸氢钙(DCPA)细粉末混合，按甲壳素纤维占磷酸四钙(TTCP)与磷酸氢钙(DCPA)细粉末总重量比5％加入长度为10mm甲壳素纤维，混合均匀。在0.2M的磷酸钠缓冲液中加入占磷酸四钙(TTCP)与磷酸氢钙(DCPA)粉末总重量1.0％磷酸化壳聚糖(脱乙酰度：60％；取代度：0.50；分子量：5×103)和0.1％的骨形成蛋白rhBMP2，搅拌均匀后，按固液比(P/L)为4∶1将含有磷酸化壳聚糖和骨形成蛋白rhBMP-2的磷酸钠缓冲液在研钵中混合均匀。浆状物可直接注射到骨缺损部位。
实施例4：
将研磨后的Ca(OH)2、磷酸氢钙(DCPD)按方程(2)比例混合。将聚乙烯醇纤维与甲壳质纤维按1∶20比例编制成直径Φ50μm的梯状纤维结构，并剪成长为5cm的短纤维束。将5根短纤维束(重量为Ca(OH)2和磷酸氢钙(DCPD)粉末总重量的的0.1％)，放在直径为10mm的圆柱状容器中。在1mL 1M的Na2HPO4水溶液加入占Ca(OH)2、磷酸氢钙(DCPD)总重量10％磷酸化壳聚糖和0.1％的骨形成蛋白rhBMP-2，与固体Ca(OH)2+DCPD粉末，按固液比2∶1混合均匀。用铲子将浆状骨水泥装在圆柱状容器中，拉直纤维束，固化成形，备用。
实施例5：
将α-磷酸钙(α-TCP)、磷酸二氢钙(MCPM)和碳酸钙(Ca2CO3)细粉末按重量份数比为71∶5.8∶23.5(或12∶1∶4摩尔比)混合均匀。加入1％的长度为10mm的壳聚糖纤维及1％的磷酸化甲壳素，磷酸钠(Na3PO4)溶液(2.78mol/L)按液固比(l/s)1∶2(w/w)的比例混合制样。将固液混合后20分钟内的浆状物直接注射到骨缺损部位，用于无负重部位的修复。
实施例6：
将甲壳质纤维/聚3-羟基丁酸盐(PHB)纤维按1∶20比例编制成直径Φ为300μm的纤维束，并剪成长为10mm的短纤维束。将3％的短纤维束编成一柱状结构，放在直径为3mm的圆柱状模具中。将β-磷酸钙、磷酸二氢钙、半水合硫酸钙细粉与含0.1％的羧基化硫酸酯化壳聚糖(脱乙酰度为80％，取代度：0.8；分子量为5×105Da)蒸馏水按重量比63∶26∶10∶1混合均匀，加入到含甲壳质纤维束的圆柱状模具中，在37℃、80％湿度下固化24h。所得固化物用于癌或肿瘤切除缺损的修复，并伴有抗凝血、抗炎症效果。
实施例7：
将研磨后的Ca(OH)2、磷酸氢钙(DCPD)按方程(2)比例混合。将3-羟基丁酸和3羟基己酸共聚物[Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)，PHBHHx])纤维与甲壳质纤维按20∶1比例编制成直径Φ500μm的纤维网，并卷曲成一柱状网，放在直径为20mm的圆柱状容器中。在1M的Na2HPO4水溶液加入将5％的羧基化硫酸酯化壳聚糖(脱乙酰度：75％；取代度：0.6；分子量：6×103-Da)，待溶解后，与固体Ca(OH)2/DCPD粉末混合均匀，固液比是2.00。用铲子将浆状骨水泥装在圆柱状容器中，拉直纤维束，固化成形。此材料用于骨癌切除处。
实施例8：
将研磨后的α-磷酸钙(α-TCP)、磷酸氢钙(DCPA)、碳酸钙(Ca2CO3)、磷酸四钙[TTCP，Ca4(PO4)2]细粉末按12∶5∶2∶1(w/w)的重量百分比混合均匀。将占α-磷酸钙(α-TCP)、磷酸氢钙(DCPA)、碳酸钙(Ca2CO3)、磷酸四钙[TTCP，Ca4(PO1)2]粉末总重量2.5％的磷酸化壳聚糖(脱乙酰度：850％；取代度：0.47；分子量：4.8×103)及1％的骨形成蛋白rhBMP-2溶解在1M的Na2HPO4水溶液。将3-羟基丁酸和3-羟基己酸共聚物[Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)，PHBHHx])纤维与甲壳质纤维按(1∶20)比例编制成直径Φ100μm的纤维束，并剪成长为10cm的短纤维束。将5％的短纤维束放在直径为8cm的圆柱状容器中。与磷酸化壳聚糖与骨形成蛋白的液体相与固体粉末混合均匀，固液比是2。用铲子将浆状骨水泥装在圆柱状容器中，拉直纤维束，固化成形，备用。
实施例9：
将研磨后的Ca(OH)2、磷酸氢钙(DCPD)按方程(2)比例混合。将Vicryl Rapide纤维与甲壳质纤维按1∶20比例编制成直径Φ300μm的纤维束，并剪成长为30cm的短纤维束。将0.1％的短纤维束放在直径为6cm的圆柱状容器中。在1mL 1M的Na2HPO4水溶液中加入占Ca(OH)2与磷酸氢钙(DCPD)总重量1％的磷酸化壳聚糖及0.1％的骨形成蛋白rhBMP-2，待搅拌均匀后，与固体Ca(OH)2/DCPD粉末混合均匀，固液比是3.0。用铲子将浆状骨水泥装在圆柱状容器中，拉直纤维束，固化成形，备用。
实施例10：
将1％的PLLA溶于1，4二氧六环中，将研磨后的磷酸钙(TCP)与PLLA溶液按固/液比1∶1(w/w)比例混合成浆状物。将Vicryl Rapide纤维与甲壳质纤维按20∶1比例缠绕在一起，将0.5％的纤维束放在直径为20cm的圆柱状容器中。用铲子将浆状物装在圆柱状容器中，拉直纤维束，冻干，备用。
实施例11：
将2％的PLGA(乳酸与乙醇酸的比例为7∶3)溶于1，4二氧六环中，将研磨后的磷酸钙(TCP)中先加入2％的胶原醋酸溶液及0.2％骨形成蛋白rhBMP-2混合均匀，再与PLGA溶液按固/液比3∶1(w/w)比例混合成浆状物。将Vicryl Rapide纤维与甲壳质纤维按1∶1比例编制成直径Φ100μm的纤维束，并剪成长为30cm的短纤维束。将0.1％根短纤维束放在直径为20cm的圆柱状容器中。用铲子将浆状物装在圆柱状容器中，拉直纤维束，冻干，备用。
实施例12：
将羟基磷灰石(HA)粉末研碎，与壳聚糖/胶原醋酸溶液(1∶1v/v，壳聚糖与胶原在醋酸中的浓度均为2％)和骨形成蛋白rhBMP-2的生理盐水悬浮液(200ug/mL)按90∶9∶1，搅拌均匀。将1％羟基磷灰石(HA)粉末重量的甲壳质纤维编制成同心圆纤维网，放在直径为8mm的圆柱状容器中。用铲子将浆状羟基磷灰石/壳聚糖/胶原/骨形成蛋白混合物装在圆柱状容器中，拉直纤维束，固化成形。
Claims (9)
1.一种钙磷盐基骨修复材料，其特征在于：该材料含有钙磷盐和甲壳素/壳聚糖纤维，所述的甲壳素/壳聚糖纤维占钙磷盐总重量的0.1～5％，所述甲壳素/壳聚糖纤维以纤维丝或纤维束形式存在；所述的钙磷盐由氧化钙和磷酸二氢钙混合物，氢氧化钙和磷酸氢钙混合物，磷酸四钙与磷酸氢钙混合物，α-磷酸钙、磷酸二氢钙和碳酸钙混合物，α-磷酸钙、磷酸氢钙、碳酸钙和磷酸四钙混合物制备而成；或直接采用羟基磷灰石、磷酸钙。
2.按照权利要求1所述的骨修复材料，其特征在于：该材料还含有钙磷盐总重量0.1～10％的甲壳素衍生物，所述的甲壳素衍生物为磷酸化甲壳素、磷酸化壳聚糖或羧基化硫酸酯化壳聚。
3.按照权利要求1或2所述的骨修复材料，其特征在于：该材料还含有占钙磷盐总重量的0.01～0.1％的胶原、骨形成蛋白、甲氨蝶呤或阿霉素。
4.按照权利要求1所述的骨修复材料，其特征在于：所述的纤维丝为3～10mm长的短纤维丝，所述的纤维束为直径50～500μm，长度为2～30cm的纤维束。
5.按照权利要求1或4所述的骨修复材料，其特征在于：所述的甲壳素/壳聚糖纤维束与可降解的聚乙烯醇纤维、乳酸与乙醇酸的共聚物纤维、胶原纤维、聚乙烯醇纤维、聚3-羟基丁酸盐纤维、3羟基丁酸和3-羟基己酸共聚物纤维或聚氨酯纤维按1～20∶20～1比例混合编制成网格状、梯形状结构。
6.一种钙磷盐基骨修复材料的制备方法，其特征在于该方法按如下步骤进行：
a.首先将钙磷盐粉末与磷酸钠缓冲溶液混合制成浆状物，或将钙磷盐粉末与聚乳酸、乳酸与乙醇酸的共聚物的氯仿或1，4二氧六环溶液混合制成浆状物；
b.将甲壳素/壳聚糖纤维剪制成3～10mm长的短纤维丝，与步骤a中的浆状物搅拌混合，或编成直径为50～500μm，长度为2～30cm纤维束与步骤a中的浆状物复合；其中甲壳素/壳聚糖纤维占钙磷盐总重量的0.1～5％；
c.然后经自然凉干或将溶剂除去后形成含纤维的固态物质。
7.按照权利要求6所述的制备方法，其特征在于：在所述的步骤a中加入占钙磷盐总重量0.1～10％的甲壳素衍生物，所述的衍生物为壳聚糖、磷酸化甲壳素、磷酸化壳聚糖、羧基化硫酸酯化壳聚。
9.按照权利要求6或7所述的制备方法，其特征在于：所述的步骤a中加入占钙磷盐总重量的0.01～0.1％的胶原、骨形成蛋白、甲氨蝶呤或阿霉素。
10.按照权利要求6所述的制备方法，其特征在于：所述步骤b中的纤维束与可降解的聚乙烯醇纤维、乳酸与乙醇酸的共聚物纤维、胶原纤维、聚乙烯醇纤维、聚3-羟基丁酸盐纤维、3-羟基丁酸和3-羟基己酸共聚物纤维或聚氨酯纤维按1～20∶20～1比例混合编制成网格状、梯形状结构后再与浆状物复合。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100341093A CN1298395C (zh) | 2004-04-23 | 2004-04-23 | 一种钙磷盐基骨修复材料及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100341093A CN1298395C (zh) | 2004-04-23 | 2004-04-23 | 一种钙磷盐基骨修复材料及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1569256A CN1569256A (zh) | 2005-01-26 |
| CN1298395C true CN1298395C (zh) | 2007-02-07 |
Family
ID=34481471
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100341093A Expired - Fee Related CN1298395C (zh) | 2004-04-23 | 2004-04-23 | 一种钙磷盐基骨修复材料及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1298395C (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101229393B (zh) * | 2007-01-24 | 2013-07-17 | 张立海 | 胶原—壳聚糖—羟基磷灰石骨修复材料及其制备方法 |
| CA2863381C (en) | 2012-01-31 | 2021-11-16 | The University Of Toledo | Injectable, biodegradable bone cements and methods of making and using same |
| CN111214700A (zh) * | 2020-03-20 | 2020-06-02 | 扬州大学 | 一种抗骨肿瘤复合材料支架的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1362447A (zh) * | 2001-01-05 | 2002-08-07 | 成都迪康中科生物医学材料有限公司 | 纤维增强的聚乳酸复合物 |
| CN1456360A (zh) * | 2003-05-28 | 2003-11-19 | 东南大学 | 可吸收超细纤维组织修复材料及其制备方法 |
-
2004
- 2004-04-23 CN CNB2004100341093A patent/CN1298395C/zh not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1362447A (zh) * | 2001-01-05 | 2002-08-07 | 成都迪康中科生物医学材料有限公司 | 纤维增强的聚乳酸复合物 |
| CN1456360A (zh) * | 2003-05-28 | 2003-11-19 | 东南大学 | 可吸收超细纤维组织修复材料及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1569256A (zh) | 2005-01-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Matinfar et al. | Evaluation of physicochemical, mechanical and biological properties of chitosan/carboxymethyl cellulose reinforced with multiphasic calcium phosphate whisker-like fibers for bone tissue engineering | |
| Bharadwaz et al. | Recent trends in the application of widely used natural and synthetic polymer nanocomposites in bone tissue regeneration | |
| Januariyasa et al. | Nanofibrous poly (vinyl alcohol)/chitosan contained carbonated hydroxyapatite nanoparticles scaffold for bone tissue engineering | |
| Venkatesan et al. | Alginate composites for bone tissue engineering: A review | |
| Nge et al. | Microstructure and mechanical properties of bacterial cellulose/chitosan porous scaffold | |
| Muzzarelli | Chitosan composites with inorganics, morphogenetic proteins and stem cells, for bone regeneration | |
| Lalzawmliana et al. | Marine organisms as a source of natural matrix for bone tissue engineering | |
| Barbosa et al. | Polysaccharides as scaffolds for bone regeneration | |
| Venkatesan et al. | Chitin and chitosan composites for bone tissue regeneration | |
| CN1241657C (zh) | 一种引导硬组织再生修复的可降解材料及其制备方法 | |
| Kumar et al. | Biodegradable hydrogel‐based biomaterials with high absorbent properties for non‐adherent wound dressing | |
| CA2118218C (en) | Biomaterials for bone replacements | |
| Pramanik et al. | Natural biopolymers for bone tissue engineering: a brief review | |
| WO2003042250A1 (en) | Composition and method to homogeneously modify or cross-link chitosan under neutral conditions | |
| EP2167144A1 (en) | Biopolymer based implantable degradable devices | |
| Xing et al. | Biomedical applications of chitosan/silk fibroin composites: A review | |
| WO2008103017A1 (en) | Biodegradable porous composite and hybrid composite of biopolymers and bioceramics | |
| Singh et al. | Nanocellulose biocomposites for bone tissue engineering | |
| EP3609549B1 (en) | Connective tissues, such as bone, dentin or pulp, regenerative material comprising calcium silicate | |
| CN1298395C (zh) | 一种钙磷盐基骨修复材料及其制备方法 | |
| Liu et al. | Self-biomineralized in situ injectable CaSO4 nanorods-enriched collagen-hyaluronic acid composite hydrogels for biomimetic bone reconstruction in a minimally invasive manner | |
| Ding | Preparation and properties of chitosan/calcium phosphate composites for bone repair | |
| Petre et al. | Surface functionalization of polylactic acid fibers with alendronate groups does not improve the mechanical properties of fiber-reinforced calcium phosphate cements | |
| Namazi et al. | Bio-nanocomposites based on naturally occurring common polysaccharides chitosan, cellulose and starch with their biomedical applications | |
| CN1230181C (zh) | 一种骨修复材料 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070207 Termination date: 20130423 |