JP5647432B2 - 骨再生材料 - Google Patents
骨再生材料 Download PDFInfo
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- JP5647432B2 JP5647432B2 JP2010106774A JP2010106774A JP5647432B2 JP 5647432 B2 JP5647432 B2 JP 5647432B2 JP 2010106774 A JP2010106774 A JP 2010106774A JP 2010106774 A JP2010106774 A JP 2010106774A JP 5647432 B2 JP5647432 B2 JP 5647432B2
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- ocp
- bone
- gelatin
- calcium
- bone regeneration
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- 230000010478 bone regeneration Effects 0.000 title claims description 22
- 239000000463 material Substances 0.000 title claims description 19
- 108010010803 Gelatin Proteins 0.000 claims description 31
- 239000008273 gelatin Substances 0.000 claims description 31
- 229920000159 gelatin Polymers 0.000 claims description 31
- 235000019322 gelatine Nutrition 0.000 claims description 31
- 235000011852 gelatine desserts Nutrition 0.000 claims description 31
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 30
- 239000007864 aqueous solution Substances 0.000 claims description 21
- 239000011575 calcium Substances 0.000 claims description 17
- 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 15
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 14
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 14
- 229910052791 calcium Inorganic materials 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 13
- 239000001506 calcium phosphate Substances 0.000 claims description 12
- 235000011010 calcium phosphates Nutrition 0.000 claims description 12
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 description 46
- 239000000499 gel Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- 230000007547 defect Effects 0.000 description 16
- 102000008186 Collagen Human genes 0.000 description 14
- 108010035532 Collagen Proteins 0.000 description 14
- 229920001436 collagen Polymers 0.000 description 14
- 235000011007 phosphoric acid Nutrition 0.000 description 13
- 241000700159 Rattus Species 0.000 description 10
- 230000011164 ossification Effects 0.000 description 10
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 8
- 210000003625 skull Anatomy 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 208000006735 Periostitis Diseases 0.000 description 3
- 238000010894 electron beam technology Methods 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 210000003460 periosteum Anatomy 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- -1 β-TCP) Chemical class 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010009260 Cleft lip and palate Diseases 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000009388 chemical precipitation Methods 0.000 description 1
- 208000016653 cleft lip/palate Diseases 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 210000002997 osteoclast Anatomy 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
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Materials For Medical Uses (AREA)
Description
(OCP/Gelの熱脱水架橋体の調製)
ゼラチン(シグマ社製、Type A Gelatin(ブタ皮膚由来))をリン酸緩衝液(リン酸2水素ナトリウム)に溶解して、1%(w/v)のゼラチンを含む水溶液を調製した。このゼラチン溶液500mLを攪拌しながら70℃に維持した。この溶液に、0.08モル/Lの酢酸カルシウム水溶液500mLを7.5分間かけて滴下して混合した。滴下終了後、混合液をさらに70℃にて数分間静置することにより、沈殿(共沈物)を形成させた。上清を除去し、沈殿の懸濁液をポリプロピレン製の容器に移し、凍結乾燥を行った。凍結乾燥物を133Pa以下の減圧下、150℃にて24時間維持することにより、OCP/Gelの熱脱水架橋体を得た。得られたOCP/Gel中のOCP含有量は、化学分析の結果、約40質量%であった。
ジエチルエーテルおよびネンブタールを用いて、ラット(Wistar、12週齢、雄性)に全身麻酔を施した。次いで、ラットの頭蓋部皮膚を剃毛し、露出した皮膚およびその下の骨膜をメスで切開した。頭蓋骨正中部に直径9mmの骨欠損部を形成した。次いで、電子線照射(5kGy)により滅菌したOCP/Gelの熱脱水架橋体を、ディスク状に成形し(直径9mm、厚さ1mm)、骨欠損部に埋入して骨膜および皮膚を縫合した。
(OCP/Colの熱脱水架橋体の調製)
ブタ皮膚由来ペプシン可溶化コラーゲン凍結乾燥粉末(タイプI+タイプIII、中性、架橋あり:NMPコラーゲンPS;日本ハム株式会社製)を酸性溶液に溶解して、1%(w/v)のコラーゲンを含む水溶液を調製した。このコラーゲン溶液に、O.Suzukiら、Tohoku J. Exp. Med.、1991年、第164巻、p.37に記載の手順で製造したOCP顆粒を、OCPとコラーゲンとの質量比が77:23(OCP77質量%)となるように分散させた。この分散液をポリプロピレン製の容器に移し、凍結乾燥を行った。凍結乾燥物を133Pa以下の減圧下、150℃にて24時間維持することにより、OCP/Colの熱脱水架橋体を得た。
実施例1と同様にして、骨欠損部を形成した。次いで、電子線照射(5kGy)により滅菌したOCP/Colの熱脱水架橋体を、ディスク状に成形し(直径9mm、厚さ1mm)、骨欠損部に埋入して骨膜および皮膚を縫合した。
Claims (3)
- 第8リン酸カルシウムとゼラチンとの共沈物の熱脱水架橋体を含む骨再生材料。
- 骨再生材料の製造方法であって、
ゼラチンおよびリン酸を含む水溶液に、カルシウム水溶液を滴下または注加して、第8リン酸カルシウムとゼラチンとの共沈物を得る工程、および
該共沈物を加熱して熱脱水架橋体を得る工程
を含む、方法。 - 骨再生材料の製造方法であって、
ゼラチンおよびカルシウムを含む水溶液に、リン酸水溶液を滴下または注加して、第8リン酸カルシウムとゼラチンとの共沈物を得る工程、および
該共沈物を加熱して熱脱水架橋体を得る工程
を含む、方法。
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JP5647432B2 true JP5647432B2 (ja) | 2014-12-24 |
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Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5881206B2 (ja) * | 2011-11-17 | 2016-03-09 | ニプロ株式会社 | 骨再生材料 |
KR101638834B1 (ko) * | 2012-03-12 | 2016-07-12 | 후지필름 가부시키가이샤 | 조직 수복재의 제조 방법 |
JP2013202213A (ja) * | 2012-03-28 | 2013-10-07 | Fujifilm Corp | 硬組織再生用材料 |
JP6265665B2 (ja) * | 2013-09-11 | 2018-01-24 | 国立大学法人東北大学 | 骨接合部再生材料 |
US10064979B2 (en) | 2013-12-02 | 2018-09-04 | Tohoku University | Bone regeneration material |
JPWO2023095781A1 (ja) * | 2021-11-24 | 2023-06-01 | ||
JP2023155671A (ja) * | 2022-04-11 | 2023-10-23 | 国立研究開発法人産業技術総合研究所 | 生体親和性高分子を複合化したリン酸八カルシウム成形体の製造方法 |
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JPS62194354U (ja) * | 1986-05-31 | 1987-12-10 | ||
JP3592920B2 (ja) * | 1998-01-19 | 2004-11-24 | 独立行政法人物質・材料研究機構 | 有機無機配向性複合材料の製造方法 |
CA2319969A1 (en) * | 1999-09-24 | 2001-03-24 | Isotis B.V. | Composites |
WO2003092759A1 (fr) * | 2002-05-01 | 2003-11-13 | Japan Science And Technology Agency | Procede de preparation d'un materiau composite poreux |
JP5046511B2 (ja) * | 2004-11-19 | 2012-10-10 | 日本ハム株式会社 | 硬組織代替性担体材料 |
JP2008279008A (ja) * | 2007-05-09 | 2008-11-20 | Olympus Terumo Biomaterials Corp | リン酸カルシウム成形体の製造方法 |
ITMI20071298A1 (it) * | 2007-06-29 | 2008-12-30 | Univ Bologna Alma Mater | Materiale composito poroso, relativo processo di preparazione e suo uso per la realizzazione di dispositivi per l'ingegneria tissutale |
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