JP2012239697A - 人工骨膜 - Google Patents
人工骨膜 Download PDFInfo
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- JP2012239697A JP2012239697A JP2011113498A JP2011113498A JP2012239697A JP 2012239697 A JP2012239697 A JP 2012239697A JP 2011113498 A JP2011113498 A JP 2011113498A JP 2011113498 A JP2011113498 A JP 2011113498A JP 2012239697 A JP2012239697 A JP 2012239697A
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- bmp
- artificial periosteum
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- 208000006735 Periostitis Diseases 0.000 title claims abstract description 34
- 210000003460 periosteum Anatomy 0.000 title claims abstract description 34
- 239000000463 material Substances 0.000 claims abstract description 40
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 claims abstract description 14
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 claims abstract description 14
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 claims abstract description 8
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims abstract description 8
- 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 claims abstract description 4
- 108010049976 Bone Morphogenetic Protein 5 Proteins 0.000 claims abstract description 4
- 108010049974 Bone Morphogenetic Protein 6 Proteins 0.000 claims abstract description 4
- 102100024505 Bone morphogenetic protein 4 Human genes 0.000 claims abstract description 4
- 102100022526 Bone morphogenetic protein 5 Human genes 0.000 claims abstract description 4
- 102100022525 Bone morphogenetic protein 6 Human genes 0.000 claims abstract description 4
- 102100022545 Bone morphogenetic protein 8B Human genes 0.000 claims abstract description 4
- 101000899368 Homo sapiens Bone morphogenetic protein 8B Proteins 0.000 claims abstract description 3
- 229920002988 biodegradable polymer Polymers 0.000 claims description 35
- 239000004621 biodegradable polymer Substances 0.000 claims description 35
- 241000588724 Escherichia coli Species 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 abstract 3
- 239000000126 substance Substances 0.000 abstract 1
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- 210000004027 cell Anatomy 0.000 description 9
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- 230000007547 defect Effects 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229920003232 aliphatic polyester Polymers 0.000 description 2
- 230000010478 bone regeneration Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
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- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
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- 210000000130 stem cell Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VSKXVGWORBZZDY-UHFFFAOYSA-N 2-hydroxypropanoic acid;oxepan-2-one Chemical compound CC(O)C(O)=O.O=C1CCCCCO1 VSKXVGWORBZZDY-UHFFFAOYSA-N 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037237 body shape Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
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- 229920001519 homopolymer Polymers 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000010030 laminating Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 230000002138 osteoinductive effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
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- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
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Abstract
【解決手段】 大腸菌由来のBMPを含んだシート状の生分解性高分子材料から成る人工骨膜とする。このとき、大腸菌由来のBMPが、宿主細胞として大腸菌を用いて生産したBMPであり、BMP-2, BMP-4, BMP-5, BMP-6, BMP-7(OP-1),BMP-8(OP-2),及びこれらの機能的等価改変体(改変型BMP)からなる群より選択されるBMPの1種または2種以上であることが好ましい。
【選択図】 なし
Description
即ち本発明は、大腸菌由来のBMPを含んだシート状の生分解性高分子材料からなる人工骨膜である。
1,4−ジオキサン中に乳酸−グリコール酸共重合体(乳酸:グリコール酸=75:25、分子量約250、000)を8重量%の濃度となるように入れ撹拌器で1時間撹拌させて溶解した。溶解液を100mm×100mm、隙間2mmの型に流し込み、24時間凍結後、48時間真空乾燥させて80mm×80mm、厚み約1mmの生分解性高分子材料を得た。得られた生分解性高分子材料を金属製のプレス型にて300kgf/cm2の条件にて厚さ約0.25mmにプレスした。作製されたシート状の生分解性高分子材料は、孔のサイズが50μm、気孔率50%、厚さが0.25mmであった。
その後、シート状生分解性高分子材料を10mm×10mmの大きさにカットし、濃度1,5,10μg/μLで調製した大腸菌由来BMP-2を溶解させたリン酸緩衝液0.1mL中に4℃で24時間浸漬させた後、取り出し、凍結乾燥させることで人工骨膜を作製した。なお、凍結乾燥前後の重量測定を行ったところ、本実施例の人工骨膜にはそれぞれ、約16,80,160μgの大腸菌由来BMP-2が含まれていた。
1,4−ジオキサン中に乳酸−グリコール酸共重合体(乳酸:グリコール酸=75:25、分子量約250、000)を8重量%の濃度となるように入れ撹拌器で1時間撹拌させて溶解した。溶解液を100mm×100mm、隙間2mmの型に流し込み、24時間凍結後、48時間真空乾燥させて80mm×80mm、厚み約1mmの生分解性高分子材料を得た。得られた生分解性高分子材料を隙間約0.25mmの金属製のプレス型にて300kgf/cm2の条件にて厚さ約0.25mmにプレスした。作製されたシート状の生分解性高分子材料は、孔のサイズが50μm、気孔率50%、厚さが0.25mmであった。
その後、シート状生分解性高分子材料を10mm×10mmの大きさにカットし、濃度1,5,10μg/μLで調製した哺乳動物細胞を利用したBMP-2を溶解させたリン酸緩衝液0.1mL中に4℃で24時間浸漬させた後、取り出し、凍結乾燥させることで人工骨膜を作製した。なお、凍結乾燥前後の重量測定を行ったところ、本実施例の人工骨膜にはそれぞれ、約16,80,160μgの哺乳動物細胞を利用したBMP-2が含まれていた。
哺乳動物由来BMP-2の製造コスト:¥10,000/mg
Claims (4)
- 大腸菌由来のBMPを含んだシート状の生分解性高分子材料から成る人工骨膜。
- 大腸菌由来のBMPが、宿主細胞として大腸菌を用いて生産したBMPであり、BMP-2, BMP-4, BMP-5, BMP-6, BMP-7(OP-1),BMP-8(OP-2),及びこれらの機能的等価改変体(改変型BMP)からなる群より選択されるBMPの1種または2種以上である請求項1に記載の人工骨膜。
- 大腸菌由来のBMPが溶解された水溶液にシート状の生分解性高分子材料を浸漬させた後、取り出して凍結乾燥させる人工骨膜の作製方法。
- 大腸菌由来のBMPが、宿主細胞として大腸菌を用いて生産したBMPであり、BMP-2, BMP-4, BMP-5, BMP-6, BMP-7(OP-1),MP-8(OP-2),及びこれらの機能的等価改変体(改変型BMP)からなる群より選択されるBMPの1種または2種以上である請求項3に記載の人工骨膜の作製方法。
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JP2011113498A JP5924610B2 (ja) | 2011-05-20 | 2011-05-20 | 人工骨膜の作製方法 |
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JP2012239697A true JP2012239697A (ja) | 2012-12-10 |
JP5924610B2 JP5924610B2 (ja) | 2016-05-25 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2022500157A (ja) * | 2018-09-14 | 2022-01-04 | オーソセル・リミテッド | 人工骨膜 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH053913A (ja) * | 1991-06-26 | 1993-01-14 | Sumitomo Cement Co Ltd | 人工生体複合材料 |
WO1996010426A1 (fr) * | 1994-09-30 | 1996-04-11 | Yamanouchi Pharmaceutical Co., Ltd. | Greffon osteoplastique |
JP2002502822A (ja) * | 1998-02-10 | 2002-01-29 | オレゴン ヘルス サイエンシーズ ユニバーシティー | 骨芽細胞の前駆細胞による骨欠損の治療 |
JP2003275294A (ja) * | 2002-03-25 | 2003-09-30 | Olympus Optical Co Ltd | 骨再生シート |
US20060045902A1 (en) * | 2004-09-01 | 2006-03-02 | Serbousek Jon C | Polymeric wrap for in vivo delivery of osteoinductive formulations |
JP2007332106A (ja) * | 2006-06-16 | 2007-12-27 | Okayama Univ | 骨形成用徐放性医薬組成物 |
JP2009045142A (ja) * | 2007-08-16 | 2009-03-05 | Okayama Univ | 生体内にて基材周囲に骨形成を誘導するための基材処理方法 |
WO2009129631A1 (en) * | 2008-04-21 | 2009-10-29 | Ao Technology Ag | Biocompatible implant |
JP2010500905A (ja) * | 2006-08-17 | 2010-01-14 | ウォーソー・オーソペディック・インコーポレーテッド | 組織再生に有用な医療インプラントシート |
-
2011
- 2011-05-20 JP JP2011113498A patent/JP5924610B2/ja active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH053913A (ja) * | 1991-06-26 | 1993-01-14 | Sumitomo Cement Co Ltd | 人工生体複合材料 |
WO1996010426A1 (fr) * | 1994-09-30 | 1996-04-11 | Yamanouchi Pharmaceutical Co., Ltd. | Greffon osteoplastique |
JP2002502822A (ja) * | 1998-02-10 | 2002-01-29 | オレゴン ヘルス サイエンシーズ ユニバーシティー | 骨芽細胞の前駆細胞による骨欠損の治療 |
JP2003275294A (ja) * | 2002-03-25 | 2003-09-30 | Olympus Optical Co Ltd | 骨再生シート |
US20060045902A1 (en) * | 2004-09-01 | 2006-03-02 | Serbousek Jon C | Polymeric wrap for in vivo delivery of osteoinductive formulations |
JP2007332106A (ja) * | 2006-06-16 | 2007-12-27 | Okayama Univ | 骨形成用徐放性医薬組成物 |
JP2010500905A (ja) * | 2006-08-17 | 2010-01-14 | ウォーソー・オーソペディック・インコーポレーテッド | 組織再生に有用な医療インプラントシート |
JP2009045142A (ja) * | 2007-08-16 | 2009-03-05 | Okayama Univ | 生体内にて基材周囲に骨形成を誘導するための基材処理方法 |
WO2009129631A1 (en) * | 2008-04-21 | 2009-10-29 | Ao Technology Ag | Biocompatible implant |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2022500157A (ja) * | 2018-09-14 | 2022-01-04 | オーソセル・リミテッド | 人工骨膜 |
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