JP5201510B2 - 骨誘導性リン酸カルシウム - Google Patents
骨誘導性リン酸カルシウム Download PDFInfo
- Publication number
- JP5201510B2 JP5201510B2 JP2008555181A JP2008555181A JP5201510B2 JP 5201510 B2 JP5201510 B2 JP 5201510B2 JP 2008555181 A JP2008555181 A JP 2008555181A JP 2008555181 A JP2008555181 A JP 2008555181A JP 5201510 B2 JP5201510 B2 JP 5201510B2
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- JP
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- Prior art keywords
- tricalcium phosphate
- porous
- tcp
- osteoinductive
- ceramic
- 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.)
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 title claims description 233
- 239000001506 calcium phosphate Substances 0.000 title claims description 121
- 235000011010 calcium phosphates Nutrition 0.000 title claims description 87
- 229910000389 calcium phosphate Inorganic materials 0.000 title claims description 84
- 235000019731 tricalcium phosphate Nutrition 0.000 claims description 134
- 239000002245 particle Substances 0.000 claims description 98
- 239000000463 material Substances 0.000 claims description 97
- 239000000843 powder Substances 0.000 claims description 80
- 230000002138 osteoinductive effect Effects 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 48
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 102000004169 proteins and genes Human genes 0.000 claims description 47
- 210000000988 bone and bone Anatomy 0.000 claims description 40
- 239000007943 implant Substances 0.000 claims description 40
- 239000002002 slurry Substances 0.000 claims description 39
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 36
- 229940078499 tricalcium phosphate Drugs 0.000 claims description 33
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 31
- 239000012091 fetal bovine serum Substances 0.000 claims description 28
- 238000001179 sorption measurement Methods 0.000 claims description 28
- 239000011575 calcium Substances 0.000 claims description 27
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 26
- 239000011859 microparticle Substances 0.000 claims description 24
- 239000011148 porous material Substances 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 21
- 239000000758 substrate Substances 0.000 claims description 20
- 238000005245 sintering Methods 0.000 claims description 19
- 239000004604 Blowing Agent Substances 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 12
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical group [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 12
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 8
- 229910052586 apatite Inorganic materials 0.000 claims description 8
- 230000001788 irregular Effects 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000000227 grinding Methods 0.000 claims description 6
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[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 VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000005187 foaming Methods 0.000 claims description 5
- 239000004088 foaming agent Substances 0.000 claims description 5
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003102 growth factor Substances 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 229910000392 octacalcium phosphate Inorganic materials 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- YIGWVOWKHUSYER-UHFFFAOYSA-F tetracalcium;hydrogen phosphate;diphosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].OP([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O YIGWVOWKHUSYER-UHFFFAOYSA-F 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 239000010419 fine particle Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000002407 tissue scaffold Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000003796 beauty Effects 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000000919 ceramic Substances 0.000 description 106
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- 241000282472 Canis lupus familiaris Species 0.000 description 8
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
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- JUNWLZAGQLJVLR-UHFFFAOYSA-J calcium diphosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O JUNWLZAGQLJVLR-UHFFFAOYSA-J 0.000 description 4
- 235000019821 dicalcium diphosphate Nutrition 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 4
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- 239000007858 starting material Substances 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 210000002449 bone cell Anatomy 0.000 description 3
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- 229940043256 calcium pyrophosphate Drugs 0.000 description 3
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- 239000012894 fetal calf serum Substances 0.000 description 3
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- 235000019691 monocalcium phosphate Nutrition 0.000 description 3
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- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 2
- JUQPZRLQQYSMEQ-UHFFFAOYSA-N CI Basic red 9 Chemical compound [Cl-].C1=CC(N)=CC=C1C(C=1C=CC(N)=CC=1)=C1C=CC(=[NH2+])C=C1 JUQPZRLQQYSMEQ-UHFFFAOYSA-N 0.000 description 2
- 239000005574 MCPA Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- WHKUVVPPKQRRBV-UHFFFAOYSA-N Trasan Chemical compound CC1=CC(Cl)=CC=C1OCC(O)=O WHKUVVPPKQRRBV-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 229940052223 basic fuchsin Drugs 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- VEJCUEBBRSCJRP-UHFFFAOYSA-L calcium;hydron;phosphonato phosphate Chemical compound [Ca+2].OP(O)(=O)OP([O-])([O-])=O VEJCUEBBRSCJRP-UHFFFAOYSA-L 0.000 description 2
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- 230000000877 morphologic effect Effects 0.000 description 2
- RFWLACFDYFIVMC-UHFFFAOYSA-D pentacalcium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O RFWLACFDYFIVMC-UHFFFAOYSA-D 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
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- ZRMMVODKVLXCBB-UHFFFAOYSA-N 1-n-cyclohexyl-4-n-phenylbenzene-1,4-diamine Chemical compound C1CCCCC1NC(C=C1)=CC=C1NC1=CC=CC=C1 ZRMMVODKVLXCBB-UHFFFAOYSA-N 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 239000004134 Dicalcium diphosphate Substances 0.000 description 1
- HECLRDQVFMWTQS-UHFFFAOYSA-N Dicyclopentadiene Chemical compound C1C2C3CC=CC3C1C=C2 HECLRDQVFMWTQS-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010049811 Extraskeletal ossification Diseases 0.000 description 1
- 208000034970 Heterotopic Ossification Diseases 0.000 description 1
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- 230000002378 acidificating effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- 235000019815 calcium dihydrogen diphosphate Nutrition 0.000 description 1
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- ROPDWRCJTIRLTR-UHFFFAOYSA-L calcium metaphosphate Chemical compound [Ca+2].[O-]P(=O)=O.[O-]P(=O)=O ROPDWRCJTIRLTR-UHFFFAOYSA-L 0.000 description 1
- 229910000394 calcium triphosphate Inorganic materials 0.000 description 1
- GFIKIVSYJDVOOZ-UHFFFAOYSA-L calcium;fluoro-dioxido-oxo-$l^{5}-phosphane Chemical compound [Ca+2].[O-]P([O-])(F)=O GFIKIVSYJDVOOZ-UHFFFAOYSA-L 0.000 description 1
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- RBLGLDWTCZMLRW-UHFFFAOYSA-K dicalcium phosphate dihydrate Substances O.O.[Ca+2].[Ca+2].[O-]P([O-])([O-])=O RBLGLDWTCZMLRW-UHFFFAOYSA-K 0.000 description 1
- OLSDWRNWUGHKSY-UHFFFAOYSA-J dicalcium;phosphonato phosphate;dihydrate Chemical compound O.O.[Ca+2].[Ca+2].[O-]P([O-])(=O)OP([O-])([O-])=O OLSDWRNWUGHKSY-UHFFFAOYSA-J 0.000 description 1
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- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
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Description
本発明は、骨誘導性物質、該物質を調製する方法及びそのように製造された物質に関係する。
患者の自身の骨から採取された自己由来の骨は、大きな骨欠損の修復にとっての究極の骨代用物である。しかしながら、患者から採取可能な自己由来の骨の量は限定され、そして骨の引き抜きそれ自身が重大な健康リスクを生じ且つ残っている骨の構造的完全性の喪失を結果する。
本発明の多孔性リン酸カルシウムに関する。
−リン酸α−トリカルシウム(α−TCP、α−Ca3(PO4)2、同義語:ウィットロッカイト、リン酸トリカルシウム、リン酸カルシウムトリベーシック)、無水又は水和物として;
−リン酸β−トリカルシウム(β−TCP、β−Ca3(PO4)2、同義語:ウィットロッカイト、リン酸トリカルシウム、リン酸カルシウムトリベーシック)無水又は水和物として;
−非晶質リン酸カルシウム(ACP、Ca3(PO4)2・nH2O、n=3〜4.5、Ca/P比=1.5)
−アパタイト(カルシウムフルオロ−ホスフェート、Ca5(F、Cl、OH)(PO4)3)
−カルシウムジハイドロジェンホスフェート(Ca(H2PO4)2);
−カルシウムジハイドロジェンホスフェートハイドレート(Ca(H2PO4)2・H2O)
−カルシウムハイドロジェンホスフェートハイドレート(CaHPO4・2H2O);
−カルシウムハイドロジェンホスフェート、無水物(CaHPO4)、
−カルシウム欠損ヒドロキシアパタイト又は沈降ヒドロキシアパタイト(PHA)1.5〜1.67のCa/P比を有するCa10−X(HPO4)X(PO4)6−X(OH)2−X(0≦X≦1)
−カーボネートアパタイト(Ca5(PO4、CO3)3F)
−リン酸ジカルシウム無水物(DCPA、CaHPO4)
−リン酸ジカルシウム二水和物(DCPD、CaHPO4・2H2O);
−フルオロアパタイト(FA、Ca5(PO4)3F);
−ヒドロキシアパタイト(HA、Ca5(PO4)3OH、同義語;(ペンタ)カルシウムトリホスフェート);
−リン酸モノカルシウム無水物(MCPA、Ca(H2PO4)2);
−リン酸モノカルシウムモノハイドレート(MCPM、Ca(H2PO4)2・H2O);
−リン酸オクタカルシウム(OCP、Ca8H2(PO4)6・5H2O);
−オキシアパタイト(Ca10(PO4)6O);
−リン酸テトラカルシウム(TTCP、Ca4(PO4)2O);
−上記の2以上の混合物、例えばMCPM又はMCPAと他のCaP、例えばリン酸α−トリカルシウム又はリン酸β−トリカルシウム、及び
−上記の2以上の複合物、例えばβ−TCPとヒドロキシアパタイト(Ca/P−1.67)、例えば二相性リン酸カルシウム(BCP)
である。
−グレインサイズ(約10〜20μm×5〜15μmの面積を表す該物質の表面の顕微鏡写真の拡大及び検査に基づく、例えば図6において示されるようなSEM顕微鏡写真において見られるとおり、連続したマトリックスを形成する、最大の個々に認識できる「粒子群」、すなわち該セラミック物質中に埋め込まれ且つ他のグレインとその中で構造的に連結されたようなグレインの少なくとも10の平均直径);
−ミクロ孔サイズ(約10〜20μm×5〜15μmの該物質の表面領域の拡大及び検査に基づき、例えば図7において示されたような、SEM顕微鏡写真において見られるとおりの最大のミクロ孔の少なくとも10の平均直径);
−ミクロ孔の面積百分率(例えば、デジタル画像中における、選ばれた表面領域の画素の総数の百分率としての、ミクロ孔に関する画素数:該物質の断面図におけるミクロ孔の面積百分率);及び
−タンパク質吸着(例えば、25ppmのNaN3における3mlの1%ウシ胎仔血清(FBS)溶液中に浸されたときに、37℃で24時間のインキュベーション後での、多孔性セラミックの1mlの体積により吸収されたタンパク質の量、そして溶液中に残る量から吸収された量を、例えばBCA(商標)Protein Assay Kit(Pierce Biotechnology Inc., Rockford, Il, USA)を用いて決定する)。
それ故に、リン酸トリカルシウムセラミックの骨誘導的特性を改善する為に、焼結温度は、好ましくは1100℃を超えないべきであり、好ましくは約1050〜1075℃であるべきであることが結論付けられる。
Claims (29)
- 0.1〜1.50μmの範囲の平均グレイン(grain)サイズを有し、0.1〜1.50μmのサイズ範囲のミクロ孔を有する多孔性および10〜40%の範囲のミクロ孔の表面積百分率を有する多孔性骨誘導性リン酸トリカルシウム物質。
- 少なくとも40%のタンパク質吸着能力を有し、ここで該能力は、25ppmのアジ化ナトリウム(NaN3)の存在下におけるウシ胎仔血清(FBS)の1%水溶液の3mlの体積から、該リン酸トリカルシウムの1mlの体積により37℃で24時間後に吸収されたタンパク質の百分率として表される、請求項1に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 実質的にミクロ孔だけから成る多孔性を有する、請求項1又は2に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該物質が、約50〜約1500μmの粒子サイズを有する微小粒子の形態である、請求項1〜3のいずれか1項に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該微小粒子が、約200〜約300μmの粒子サイズを有する、請求項4に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該微小粒子が、212〜300μmの粒子サイズを有する、請求項5に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該リン酸トリカルシウムが、リン酸オクタカルシウム、アパタイト、ウィットロッカイト、及びそれらの組み合わせから成る群から選ばれる、請求項1〜6のいずれか1項に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該アパタイトが、ヒドロキシアパタイト、カーボネートアパタイト、又はそれらの組み合わせである、請求項7に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該ウィットロッカイトが、リン酸β−トリカルシウム、リン酸α−トリカルシウム、又はそれらの組み合わせである、請求項7に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該リン酸トリカルシウムが吸収可能なリン酸トリカルシウムである、請求項1〜9のいずれか1項に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 該吸収可能なリン酸トリカルシウムがリン酸β−トリカルシウムである、請求項10に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 医療的移植物材料又は組織足場として用いる為の、請求項1〜11のいずれか1項に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 生きている生物中の骨組織の形成を誘導することにおいて用いる為の、請求項1〜12のいずれか1項に定義された多孔性骨誘導性リン酸トリカルシウム物質。
- 移植物材料として単独で又は成長因子若しくは/及び細胞と組合せでの、非骨部分における自己由来の骨の産生において用いる為の、請求項1〜12のいずれか1項に定義された多孔性骨誘導性リン酸トリカルシウム物質。
- 単独で又は成長因子若しくは/及び細胞と組合せでの、医療的移植物又は装置の製造において用いる為の、請求項1〜12のいずれか1項に定義された多孔性骨誘導性リン酸トリカルシウム物質。
- 歯科の手術において用いる為の、請求項13〜15のいずれか1項に記載の多孔性骨誘導性リン酸トリカルシウム物質。
- 請求項1に記載の多孔性骨誘導性リン酸トリカルシウム物質を製造する方法であって、水中に、1.0〜8.0μmの粒子サイズを有するリン酸カルシウム粉、発泡剤及び任意的に孔形成剤の水性スラリーを用意すること;該スラリーの発泡を引き起こす条件に該スラリーを付すること;得られた発泡したスラリーを乾燥し、任意的に孔形成剤を除去して、多孔性の素地を用意すること、及び1050℃〜1150℃の温度で該多孔性の素地を焼結して多孔性の焼結リン酸カルシウムを用意すること;並びに任意的に該焼結リン酸カルシウムを粒子へと粉砕しそして約50〜約1500μmの粒子サイズを有する粒子を集めることを含む、上記方法。
- 2.0〜4.0μmの粒子サイズを有する該リン酸カルシウム粉の水性スラリーを用意することを含む、請求項17に記載の方法。
- 該粒子が、212及び300μmのふるいを用いて集められる、請求項17又は18に記載の方法。
- 該リン酸トリカルシウム粉が、0.01〜1.0μmの結晶サイズを有する結晶から構成される、請求項17〜19のいずれか1項に記載の方法。
- 該リン酸トリカルシウム粉が、0.05〜0.50μmの結晶サイズを有する結晶から構成される、請求項20に記載の方法。
- 該発泡剤が過酸化水素である、請求項17〜21のいずれか1項に記載の方法。
- 該孔形成剤がナフタレン粒子を含み、且つ該孔形成剤が80〜110℃で蒸発により除去される、請求項17〜22のいずれか1項に記載の方法。
- 該スラリーの発泡を引き起こす該条件が、約50〜70℃へ該スラリーを加熱することを含む、請求項17〜23のいずれか1項に記載の方法。
- 該スラリーの発泡が多孔性の素地を産生する、請求項17〜24のいずれか1項に記載の方法。
- 該乾燥され且つ発泡されたスラリーが、1050〜1100℃の温度で焼結される、請求項17〜25のいずれか1項に記載の方法。
- 該集められた微小粒子が次に、アセトン、エタノール及び/又は水により超音波的に洗浄され、そして任意的に乾燥され及び滅菌される、請求項17〜26のいずれか1項に記載の方法。
- 該リン酸トリカルシウム粉が、不規則な形を有する、オーブン乾燥され粉砕された粉である、請求項17〜27のいずれか1項に記載の方法。
- 請求項17〜28のいずれか1項に記載の方法により入手可能である多孔性骨誘導性リン酸トリカルシウム物質。
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CA2521623C (en) * | 2003-04-11 | 2015-03-17 | Etex Corporation | Osteoinductive bone material |
TWI230058B (en) * | 2003-08-05 | 2005-04-01 | Univ Nat Taiwan | Hydroxylapatite powder, porous body and method for preparing thereof |
US8029755B2 (en) | 2003-08-06 | 2011-10-04 | Angstrom Medica | Tricalcium phosphates, their composites, implants incorporating them, and method for their production |
EP1716873A1 (en) * | 2005-04-25 | 2006-11-02 | Progentix B.V. i.o. | Method of improving the osteoinductivity of bioactive materials |
US20060257492A1 (en) * | 2005-05-13 | 2006-11-16 | Depuy Products, Inc. | Suspension of calcium phosphate particulates for local delivery of therapeutic agents |
US7901650B2 (en) | 2005-06-22 | 2011-03-08 | Skeletal Kinectics, LLC | Porous beta-tricalcium phosphate and methods for producing the same |
US20110020419A1 (en) | 2006-02-17 | 2011-01-27 | Huipin Yuan | Osteoinductive calcium phosphates |
WO2007094672A1 (en) * | 2006-02-17 | 2007-08-23 | Progentix Orthobiology B.V. | Osteoinductive calcium phosphates |
EP1829564A1 (en) * | 2006-02-17 | 2007-09-05 | Progentix B.V. i.o. | Osteoinductive calcium phosphate |
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JP2009526600A (ja) | 2009-07-23 |
CA2642830A1 (en) | 2007-08-23 |
US20160067382A1 (en) | 2016-03-10 |
AU2007215625A1 (en) | 2007-08-23 |
EP1993624A1 (en) | 2008-11-26 |
AU2007215625B2 (en) | 2012-06-28 |
KR101391846B1 (ko) | 2014-05-19 |
EP1993624B1 (en) | 2011-05-04 |
US20100034865A1 (en) | 2010-02-11 |
KR20090017470A (ko) | 2009-02-18 |
US10532131B2 (en) | 2020-01-14 |
US7942934B2 (en) | 2011-05-17 |
US20200108180A1 (en) | 2020-04-09 |
WO2007094672A1 (en) | 2007-08-23 |
US11590263B2 (en) | 2023-02-28 |
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