JPH10504476A - 骨組織形成のための生物活性顆粒 - Google Patents
骨組織形成のための生物活性顆粒Info
- Publication number
- JPH10504476A JPH10504476A JP8503243A JP50324396A JPH10504476A JP H10504476 A JPH10504476 A JP H10504476A JP 8503243 A JP8503243 A JP 8503243A JP 50324396 A JP50324396 A JP 50324396A JP H10504476 A JPH10504476 A JP H10504476A
- Authority
- JP
- Japan
- Prior art keywords
- particles
- weight
- bone
- cao
- bone tissue
- 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.)
- Pending
Links
- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 46
- 239000008187 granular material Substances 0.000 title description 25
- 230000009772 tissue formation Effects 0.000 title description 4
- 230000000975 bioactive effect Effects 0.000 title description 3
- 239000002245 particle Substances 0.000 claims abstract description 61
- 238000000034 method Methods 0.000 claims abstract description 24
- 230000007547 defect Effects 0.000 claims description 25
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 12
- 235000020938 metabolic status Nutrition 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 230000036244 malformation Effects 0.000 claims description 2
- 239000005313 bioactive glass Substances 0.000 abstract description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 4
- 230000002503 metabolic effect Effects 0.000 abstract description 2
- 239000000377 silicon dioxide Substances 0.000 abstract description 2
- 238000002054 transplantation Methods 0.000 abstract description 2
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 abstract 1
- 239000000292 calcium oxide Substances 0.000 abstract 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 abstract 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 abstract 1
- 235000012239 silicon dioxide Nutrition 0.000 abstract 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 abstract 1
- 229910001948 sodium oxide Inorganic materials 0.000 abstract 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 29
- 239000011521 glass Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 14
- 230000008439 repair process Effects 0.000 description 10
- 239000011734 sodium Substances 0.000 description 9
- 238000009412 basement excavation Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000005553 drilling Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 7
- 210000001124 body fluid Anatomy 0.000 description 7
- 239000010839 body fluid Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 5
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 210000001621 ilium bone Anatomy 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000004820 osteoconduction Effects 0.000 description 4
- 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 description 4
- 101100282617 Bovine herpesvirus 1.1 (strain Cooper) gC gene Proteins 0.000 description 3
- 230000010398 acute inflammatory response Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000007797 corrosion Effects 0.000 description 3
- 238000005260 corrosion Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002639 bone cement Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000003722 extracellular fluid Anatomy 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000001539 phagocyte Anatomy 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000031873 Animal Disease Models Diseases 0.000 description 1
- 206010065687 Bone loss Diseases 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 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 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000237509 Patinopecten sp. Species 0.000 description 1
- 241000287462 Phalacrocorax carbo Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000002082 fibula Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000012784 inorganic fiber Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 210000001872 metatarsal bone Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 230000001009 osteoporotic effect Effects 0.000 description 1
- 210000004417 patella Anatomy 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 230000006941 response to substance Effects 0.000 description 1
- 235000020637 scallop Nutrition 0.000 description 1
- 210000001991 scapula Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 210000000457 tarsus Anatomy 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000000623 ulna Anatomy 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
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/025—Other specific inorganic materials not covered by A61L27/04 - A61L27/12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
- Glass Compositions (AREA)
- Prostheses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/268,510 US5658332A (en) | 1994-06-30 | 1994-06-30 | Bioactive granules for bone tissue formation |
| US08/268,510 | 1994-06-30 | ||
| PCT/US1995/007688 WO1996000536A1 (en) | 1994-06-30 | 1995-06-19 | Bioactive granules for bone tissue formation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10504476A true JPH10504476A (ja) | 1998-05-06 |
Family
ID=23023333
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8503243A Pending JPH10504476A (ja) | 1994-06-30 | 1995-06-19 | 骨組織形成のための生物活性顆粒 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5658332A (https=) |
| EP (1) | EP0869749B1 (https=) |
| JP (1) | JPH10504476A (https=) |
| AT (1) | ATE275370T1 (https=) |
| AU (1) | AU2903495A (https=) |
| DE (1) | DE69533490T2 (https=) |
| ES (1) | ES2227554T3 (https=) |
| WO (1) | WO1996000536A1 (https=) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6086374A (en) * | 1996-01-29 | 2000-07-11 | Usbiomaterials Corp. | Methods of treatment using bioactive glass |
| US5735942A (en) | 1996-02-07 | 1998-04-07 | Usbiomaterials Corporation | Compositions containing bioactive glass and their use in treating tooth hypersensitivity |
| US6224913B1 (en) | 1996-05-09 | 2001-05-01 | The Trustees Of The University Of Pennsylvania | Conditioning of bioactive glass surfaces in protein containing solutions |
| US5977204A (en) * | 1997-04-11 | 1999-11-02 | Osteobiologics, Inc. | Biodegradable implant material comprising bioactive ceramic |
| IN191261B (https=) | 1997-09-18 | 2003-10-18 | Univ Maryland | |
| US7572263B2 (en) | 1998-04-01 | 2009-08-11 | Arthrocare Corporation | High pressure applicator |
| AU3203599A (en) | 1998-04-01 | 1999-10-18 | Parallax Medical, Inc. | Pressure applicator for hard tissue implant placement |
| AU6168699A (en) | 1999-03-24 | 2000-10-09 | Parallax Medical, Inc. | Non-compliant system for delivery of implant material |
| US6143030A (en) * | 1999-03-26 | 2000-11-07 | Bristol-Myers Squibb Co. | Impaction allograft form and method of orthopaedic surgery using same |
| US6228386B1 (en) | 1999-04-23 | 2001-05-08 | Unicare Biomedical, Inc. | Compositions and methods to repair osseous defects |
| US6482427B2 (en) | 1999-04-23 | 2002-11-19 | Unicare Biomedical, Inc. | Compositions and methods for repair of osseous defects and accelerated wound healing |
| US6783515B1 (en) | 1999-09-30 | 2004-08-31 | Arthrocare Corporation | High pressure delivery system |
| US7758882B2 (en) | 2000-01-31 | 2010-07-20 | Indiana University Research And Technology Corporation | Composite biomaterial including anisometric calcium phosphate reinforcement particles and related methods |
| RU2251405C2 (ru) * | 2000-03-27 | 2005-05-10 | Шотт Глас | Композиции для косметических препаратов, средств личной гигиены, компонентов очищающего действия, пищевых добавок, способы их получения и применения |
| US6426114B1 (en) | 2000-05-02 | 2002-07-30 | The University Of British Columbia | Sol-gel calcium phosphate ceramic coatings and method of making same |
| US7204875B2 (en) | 2001-10-24 | 2007-04-17 | Pentron Clinical Technologies, Llc | Dental filling material |
| US7204874B2 (en) | 2001-10-24 | 2007-04-17 | Pentron Clinical Technologies, Llc | Root canal filling material |
| US7750063B2 (en) | 2001-10-24 | 2010-07-06 | Pentron Clinical Technologies, Llc | Dental filling material |
| US7303817B2 (en) | 2001-10-24 | 2007-12-04 | Weitao Jia | Dental filling material |
| US7211136B2 (en) | 2001-10-24 | 2007-05-01 | Pentron Clinical Technologies, Llc | Dental filling material |
| GB2390848B (en) * | 2002-07-15 | 2006-05-17 | Pentax Corp | CaO-SiO2-based bioactive glass and sintered calcium phosphate glass using same |
| US20050118236A1 (en) * | 2002-12-03 | 2005-06-02 | Gentis Inc. | Bioactive, resorbable scaffolds for tissue engineering |
| US8715744B2 (en) * | 2003-05-22 | 2014-05-06 | Artoss Gmbh | Inorganic resorbable bone substitute material |
| US8029755B2 (en) | 2003-08-06 | 2011-10-04 | Angstrom Medica | Tricalcium phosphates, their composites, implants incorporating them, and method for their production |
| JP3793532B2 (ja) * | 2003-10-14 | 2006-07-05 | ペンタックス株式会社 | ＣａＯ−ＭｇＯ−ＳｉＯ２系生体活性ガラス及びそれを用いたリン酸カルシウム焼結体 |
| US8287914B2 (en) * | 2006-01-12 | 2012-10-16 | Rutgers, The State University Of New Jersey | Biomimetic hydroxyapatite synthesis |
| US20100040668A1 (en) * | 2006-01-12 | 2010-02-18 | Rutgers, The State University Of New Jersey | Biomimetic Hydroxyapatite Composite Materials and Methods for the Preparation Thereof |
| GB2436067A (en) * | 2006-03-17 | 2007-09-19 | Apatech Ltd | A flowable biomedical filler resisiting flow at higher shear stress or compressive force |
| WO2009144455A2 (en) * | 2008-05-27 | 2009-12-03 | Imperial Innovations Limited | Process for producing porous scaffolds from sinterable glass |
| GB0911365D0 (en) | 2009-06-30 | 2009-08-12 | Bioceramic Therapeutics Ltd | Multicomponent glasses for use as coatings and in personal care products |
| CN102188750A (zh) * | 2010-03-10 | 2011-09-21 | 中国人民解放军总医院第一附属医院 | 一种掺锶的骨修复材料及制备方法 |
| US8722080B2 (en) * | 2011-03-11 | 2014-05-13 | Gary D. Hack | Treatment and prevention of dental pathology in humans and non-human animals |
| AU2012329012B2 (en) | 2011-10-24 | 2016-04-07 | Synergy Biomedical Llc | Compositions and their use in bone healing |
| CN102531385A (zh) * | 2012-01-17 | 2012-07-04 | 上海中山医疗科技发展公司 | 一种生物活性玻璃及其制备方法 |
| EP3678602A4 (en) | 2017-09-08 | 2021-10-06 | Pioneer Surgical Technology, Inc. | DISC IMPLANTS, INSTRUMENTS AND PROCEDURES |
| USD907771S1 (en) | 2017-10-09 | 2021-01-12 | Pioneer Surgical Technology, Inc. | Intervertebral implant |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3981736A (en) * | 1973-05-23 | 1976-09-21 | Ernst Leitz G.M.B.H. | Biocompatible glass ceramic material |
| US3905047A (en) * | 1973-06-27 | 1975-09-16 | Posta Jr John J | Implantable ceramic bone prosthesis |
| DE2501683C3 (de) * | 1975-01-17 | 1979-11-29 | Ernst Leitz Wetzlar Gmbh, 6300 Wetzlar | Polymeres Verbundmaterial für prothetische Zwecke und Verfahren zu seiner Herstellung |
| US4159358A (en) * | 1977-05-19 | 1979-06-26 | Board Of Regents, State Of Florida | Method of bonding a bioglass to metal |
| DE2724814C3 (de) * | 1977-06-02 | 1980-03-27 | Kulzer & Co Gmbh, 6380 Bad Homburg | Vorprodukt fur die Zubereitung von Knochenzement |
| BE895229A (fr) * | 1982-12-02 | 1983-03-31 | Wallone Region | Materiaux bioreactifs |
| US4786555A (en) * | 1983-10-27 | 1988-11-22 | E. I. Du Pont De Nemours And Company | Support particles coated with or particles of precursors for or of biologically active glass |
| US4608350A (en) * | 1983-10-27 | 1986-08-26 | E. I. Du Pont De Nemours And Company | Precursor solutions for biologically active glass |
| US4563350A (en) * | 1984-10-24 | 1986-01-07 | Collagen Corporation | Inductive collagen based bone repair preparations |
| US4851046A (en) * | 1985-06-19 | 1989-07-25 | University Of Florida | Periodontal osseous defect repair |
| US4889833A (en) * | 1986-10-06 | 1989-12-26 | Kuraray Co., Ltd. | Granular inorganic moldings and a process for production thereof |
| FR2606282B1 (fr) * | 1986-11-12 | 1994-05-20 | Ecole Nale Sup Ceramique Indle | Composition durcissable pour le comblement des cavites osseuses |
| DE3903695A1 (de) * | 1989-02-08 | 1990-08-09 | Merck Patent Gmbh | Resorbierbare knochenkeramik auf basis von tricalciumphosphat |
| FR2646084B1 (fr) * | 1989-04-20 | 1994-09-16 | Fbfc International Sa | Materiau bioreactif de remplissage de cavites osseuses |
| US5074916A (en) * | 1990-05-18 | 1991-12-24 | Geltech, Inc. | Alkali-free bioactive sol-gel compositions |
| WO1993017976A1 (en) * | 1992-03-09 | 1993-09-16 | Turku Implant Team Oy | Bioactive glass as a bone substitute |
-
1994
- 1994-06-30 US US08/268,510 patent/US5658332A/en not_active Expired - Lifetime
-
1995
- 1995-06-19 AT AT95924602T patent/ATE275370T1/de not_active IP Right Cessation
- 1995-06-19 DE DE69533490T patent/DE69533490T2/de not_active Expired - Fee Related
- 1995-06-19 ES ES95924602T patent/ES2227554T3/es not_active Expired - Lifetime
- 1995-06-19 JP JP8503243A patent/JPH10504476A/ja active Pending
- 1995-06-19 AU AU29034/95A patent/AU2903495A/en not_active Abandoned
- 1995-06-19 WO PCT/US1995/007688 patent/WO1996000536A1/en not_active Ceased
- 1995-06-19 EP EP95924602A patent/EP0869749B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0869749B1 (en) | 2004-09-08 |
| EP0869749A1 (en) | 1998-10-14 |
| AU2903495A (en) | 1996-01-25 |
| DE69533490T2 (de) | 2005-01-20 |
| EP0869749A4 (https=) | 1998-10-14 |
| ES2227554T3 (es) | 2005-04-01 |
| DE69533490D1 (de) | 2004-10-14 |
| WO1996000536A1 (en) | 1996-01-11 |
| US5658332A (en) | 1997-08-19 |
| ATE275370T1 (de) | 2004-09-15 |
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