SI1020185T1 - Opioid analgesics with controlled release - Google Patents
Opioid analgesics with controlled releaseInfo
- Publication number
- SI1020185T1 SI1020185T1 SI9930501T SI9930501T SI1020185T1 SI 1020185 T1 SI1020185 T1 SI 1020185T1 SI 9930501 T SI9930501 T SI 9930501T SI 9930501 T SI9930501 T SI 9930501T SI 1020185 T1 SI1020185 T1 SI 1020185T1
- Authority
- SI
- Slovenia
- Prior art keywords
- controlled release
- opioid analgesics
- opioid
- analgesics
- release
- Prior art date
Links
- 238000013270 controlled release Methods 0.000 title 1
- 239000000014 opioid analgesic Substances 0.000 title 1
- 229940005483 opioid analgesics Drugs 0.000 title 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19901687A DE19901687B4 (de) | 1999-01-18 | 1999-01-18 | Opioide Analgetika mit kontrollierter Wirkstofffreisetzung |
| EP99125470A EP1020185B1 (de) | 1999-01-18 | 1999-12-21 | Opioide Analgetika mit kontrollierter Wirkstofffreisetzung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI1020185T1 true SI1020185T1 (en) | 2004-04-30 |
Family
ID=7894566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9930501T SI1020185T1 (en) | 1999-01-18 | 1999-12-21 | Opioid analgesics with controlled release |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6685964B1 (xx) |
| EP (1) | EP1020185B1 (xx) |
| JP (1) | JP2000212072A (xx) |
| KR (1) | KR20000071247A (xx) |
| CN (1) | CN1244327C (xx) |
| AR (1) | AR022254A1 (xx) |
| AT (1) | ATE257012T1 (xx) |
| AU (1) | AU771064B2 (xx) |
| CA (1) | CA2295471A1 (xx) |
| CO (1) | CO5251462A1 (xx) |
| DE (2) | DE19901687B4 (xx) |
| DK (1) | DK1020185T3 (xx) |
| ES (1) | ES2213971T3 (xx) |
| HU (1) | HUP0000138A3 (xx) |
| IL (1) | IL134076A (xx) |
| NZ (1) | NZ502261A (xx) |
| PE (1) | PE20001395A1 (xx) |
| PL (1) | PL337867A1 (xx) |
| PT (1) | PT1020185E (xx) |
| RU (1) | RU2239417C2 (xx) |
| SI (1) | SI1020185T1 (xx) |
| SK (1) | SK285129B6 (xx) |
| ZA (1) | ZA200000173B (xx) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102716101A (zh) | 1999-10-29 | 2012-10-10 | 欧罗赛铁克股份有限公司 | 控释氢可酮制剂 |
| US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
| EP1190712B1 (en) * | 2000-09-22 | 2004-09-01 | SMB Technology | Oral once daily tramadol beads composition |
| CN100518827C (zh) | 2000-10-30 | 2009-07-29 | 欧罗赛铁克股份有限公司 | 控释氢可酮制剂 |
| CA2446738C (en) * | 2001-05-11 | 2012-05-29 | Endo Pharmaceuticals, Inc. | Abuse-resistant opioid dosage form |
| US8206741B2 (en) | 2001-06-01 | 2012-06-26 | Pozen Inc. | Pharmaceutical compositions for the coordinated delivery of NSAIDs |
| DE10141650C1 (de) | 2001-08-24 | 2002-11-28 | Lohmann Therapie Syst Lts | Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen |
| EP1476155A4 (en) * | 2002-01-23 | 2009-10-28 | Univ California | METHODS AND COMPOSITIONS FOR REDUCING THE DEVELOPMENT OF DRUG TOLERANCE AND / OR PHYSICAL DEPENDENCE |
| US20050182056A9 (en) * | 2002-02-21 | 2005-08-18 | Seth Pawan | Modified release formulations of at least one form of tramadol |
| US8128957B1 (en) | 2002-02-21 | 2012-03-06 | Valeant International (Barbados) Srl | Modified release compositions of at least one form of tramadol |
| US20040156844A1 (en) * | 2002-05-22 | 2004-08-12 | Curtis Wright | Tamper resistant oral dosage form |
| WO2004026308A1 (en) * | 2002-09-21 | 2004-04-01 | Shuyi Zhang | Sustained release compound of acetamidophenol and tramadol |
| TWI319713B (en) | 2002-10-25 | 2010-01-21 | Sustained-release tramadol formulations with 24-hour efficacy | |
| US8487002B2 (en) | 2002-10-25 | 2013-07-16 | Paladin Labs Inc. | Controlled-release compositions |
| EP1610767B1 (en) | 2003-03-26 | 2011-01-19 | Egalet A/S | Morphine controlled release system |
| CN100336501C (zh) * | 2003-08-06 | 2007-09-12 | 健乔信元医药生技股份有限公司 | 醋炎痛缓释性圆粒组成物及制备方法 |
| US20060172006A1 (en) * | 2003-10-10 | 2006-08-03 | Vincent Lenaerts | Sustained-release tramadol formulations with 24-hour clinical efficacy |
| EP1754471A1 (de) * | 2005-08-18 | 2007-02-21 | ORAMON-Arzneimittel GmbH & Co. KG | Verwendung einer quellbaren Zwischenschicht zur Steuerung des Freisetzungsprofils einer festen Arzneimittelformulierung zur peroralen Anwendung und diese enthaltende Arzneimittelformulierung |
| KR101655455B1 (ko) * | 2005-09-09 | 2016-09-07 | 안젤리니 라보팜 엘엘씨 | 일일 1회 투여를 위한 트라조돈 조성물 |
| AU2006308448A1 (en) | 2005-09-09 | 2007-05-03 | Labopharm (Barbados) Limited | Sustained drug release composition |
| US8343546B2 (en) * | 2005-09-13 | 2013-01-01 | Coating Place, Inc. | Ion exchange resin treated to control swelling |
| US7842312B2 (en) | 2005-12-29 | 2010-11-30 | Cordis Corporation | Polymeric compositions comprising therapeutic agents in crystalline phases, and methods of forming the same |
| US20070190141A1 (en) * | 2006-02-16 | 2007-08-16 | Aaron Dely | Extended release opiate composition |
| US9265732B2 (en) * | 2006-03-06 | 2016-02-23 | Pozen Inc. | Dosage forms for administering combinations of drugs |
| EA020867B1 (ru) * | 2006-03-06 | 2015-02-27 | Поузен Инк. | Лекарственные формы для введения комбинаций лекарственных средств |
| US20080069891A1 (en) * | 2006-09-15 | 2008-03-20 | Cima Labs, Inc. | Abuse resistant drug formulation |
| US8445018B2 (en) | 2006-09-15 | 2013-05-21 | Cima Labs Inc. | Abuse resistant drug formulation |
| GB0625646D0 (en) * | 2006-12-21 | 2007-01-31 | Jagotec Ag | Improvements in or relating to organic compounds |
| WO2008148798A2 (en) | 2007-06-04 | 2008-12-11 | Egalet A/S | Controlled release pharmaceutical compositions for prolonged effect |
| GB0714790D0 (en) * | 2007-07-30 | 2007-09-12 | Jagotec Ag | Improvements in or relating to organic compounds |
| BRPI0918492A2 (pt) | 2008-09-09 | 2015-12-01 | Astrazeneca Ab | uso de naproxen, ou sal farmaceuticamente aceitável do mesmo, e esomeprazol, ou sal farmaceuticamente aceitável do mesmo |
| CA2751667C (en) | 2009-02-06 | 2016-12-13 | Egalet Ltd. | Immediate release composition resistant to abuse by intake of alcohol |
| DK3045043T3 (da) * | 2009-02-26 | 2020-08-03 | Relmada Therapeutics Inc | Orale farmaceutiske sammensætninger af 3-hydroxy-n-methylmorphinan med forlænget frigivelse og fremgangsmåde til anvendelse |
| NZ597283A (en) | 2009-06-24 | 2013-07-26 | Egalet Ltd | Controlled release formulations |
| EP2445499A4 (en) | 2009-06-25 | 2013-02-27 | Astrazeneca Ab | METHOD FOR TREATING A PATIENT WITH RISK OF DEVELOPING A NSAID-ASSOCIATED SPURGE |
| EA021112B1 (ru) * | 2009-06-25 | 2015-04-30 | Поузен Инк. | Способ лечения боли и/или воспаления у пациента, нуждающегося в аспириновой терапии |
| CA2798702A1 (en) | 2010-05-11 | 2011-11-17 | Cima Labs Inc. | Alcoholresistant metoprolol-containing extended-release oral dosage forms |
| CA2860231A1 (en) | 2011-12-28 | 2013-07-04 | Pozen Inc. | Improved compositions and methods for delivery of omeprazole plus acetylsalicylic acid |
| PL2872121T3 (pl) | 2012-07-12 | 2019-02-28 | SpecGx LLC | Kompozycje farmaceutyczne o przedłużonym uwalnianiu, zniechęcające do nadużywania |
| WO2015065547A1 (en) | 2013-10-31 | 2015-05-07 | Cima Labs Inc. | Immediate release abuse-deterrent granulated dosage forms |
| US9861629B1 (en) | 2015-10-07 | 2018-01-09 | Banner Life Sciences Llc | Opioid abuse deterrent dosage forms |
| US10335405B1 (en) | 2016-05-04 | 2019-07-02 | Patheon Softgels, Inc. | Non-burst releasing pharmaceutical composition |
| CN106176683B (zh) * | 2016-08-31 | 2019-04-16 | 贵州益康制药有限公司 | 一种盐酸曲马多缓释胶囊及其制备方法和用途 |
| US10335375B2 (en) | 2017-05-30 | 2019-07-02 | Patheon Softgels, Inc. | Anti-overingestion abuse deterrent compositions |
| KR102810926B1 (ko) | 2017-12-20 | 2025-05-22 | 퍼듀 퍼머 엘피 | 남용 억제 황산모르핀 제형 |
| US20220062200A1 (en) | 2019-05-07 | 2022-03-03 | Clexio Biosciences Ltd. | Abuse-deterrent dosage forms containing esketamine |
| US11324707B2 (en) | 2019-05-07 | 2022-05-10 | Clexio Biosciences Ltd. | Abuse-deterrent dosage forms containing esketamine |
| CN120857928A (zh) * | 2023-03-17 | 2025-10-28 | 浙江大学 | 一种控释制剂及其制备方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3306250A1 (de) * | 1983-02-23 | 1984-08-23 | Basf Ag, 6700 Ludwigshafen | Sphaerische einkristalle fuer pharmazeutische zwecke |
| AU571312B2 (en) * | 1984-02-10 | 1988-04-14 | Nycomed Danmark A/S | Diffusion coated multiple-units dosage form |
| US5095151A (en) * | 1985-05-21 | 1992-03-10 | American Home Products Corporation | Preparation of propranolol hydrochloride macrocrystals |
| US5091188A (en) * | 1990-04-26 | 1992-02-25 | Haynes Duncan H | Phospholipid-coated microcrystals: injectable formulations of water-insoluble drugs |
| IL110014A (en) * | 1993-07-01 | 1999-11-30 | Euro Celtique Sa | Solid controlled-release oral dosage forms of opioid analgesics |
| EP1442745A1 (en) | 1993-10-07 | 2004-08-04 | Euro-Celtique | Orally administrable opioid formulations having extended duration of effect |
| DE69429710T2 (de) * | 1993-11-23 | 2002-08-08 | Euro-Celtique S.A., Luxemburg/Luxembourg | Verfahren zur Herstellung einer Arzneizusammensetzung mit verzögerter Wirkstoffabgabe |
| DE19630035A1 (de) * | 1996-07-25 | 1998-01-29 | Asta Medica Ag | Tramadol Multiple Unit Formulierungen |
| DK1009387T3 (da) * | 1997-07-02 | 2006-08-14 | Euro Celtique Sa | Stabiliserede tramadolformuleringer med langvarig frigivelse |
| DE19901683B4 (de) * | 1999-01-18 | 2005-07-21 | Grünenthal GmbH | Analgetikum mit kontrollierter Wirkstofffreisetzung |
-
1999
- 1999-01-18 DE DE19901687A patent/DE19901687B4/de not_active Expired - Fee Related
- 1999-12-21 DE DE59908195T patent/DE59908195D1/de not_active Expired - Lifetime
- 1999-12-21 DK DK99125470T patent/DK1020185T3/da active
- 1999-12-21 ES ES99125470T patent/ES2213971T3/es not_active Expired - Lifetime
- 1999-12-21 AT AT99125470T patent/ATE257012T1/de active
- 1999-12-21 SI SI9930501T patent/SI1020185T1/xx unknown
- 1999-12-21 EP EP99125470A patent/EP1020185B1/de not_active Expired - Lifetime
- 1999-12-21 PT PT99125470T patent/PT1020185E/pt unknown
-
2000
- 2000-01-05 AU AU10113/00A patent/AU771064B2/en not_active Ceased
- 2000-01-06 PE PE2000000012A patent/PE20001395A1/es not_active Application Discontinuation
- 2000-01-11 NZ NZ502261A patent/NZ502261A/en not_active IP Right Cessation
- 2000-01-11 AR ARP000100111A patent/AR022254A1/es unknown
- 2000-01-14 JP JP2000006879A patent/JP2000212072A/ja not_active Withdrawn
- 2000-01-14 CA CA002295471A patent/CA2295471A1/en not_active Abandoned
- 2000-01-15 KR KR1020000001839A patent/KR20000071247A/ko not_active Ceased
- 2000-01-17 IL IL13407600A patent/IL134076A/xx not_active IP Right Cessation
- 2000-01-17 CN CNB001045237A patent/CN1244327C/zh not_active Expired - Fee Related
- 2000-01-17 HU HU0000138A patent/HUP0000138A3/hu unknown
- 2000-01-17 CO CO00002029A patent/CO5251462A1/es not_active Application Discontinuation
- 2000-01-17 RU RU2000101024/15A patent/RU2239417C2/ru not_active IP Right Cessation
- 2000-01-17 SK SK64-2000A patent/SK285129B6/sk not_active IP Right Cessation
- 2000-01-17 ZA ZA200000173A patent/ZA200000173B/xx unknown
- 2000-01-17 PL PL00337867A patent/PL337867A1/xx not_active Application Discontinuation
- 2000-01-18 US US09/484,016 patent/US6685964B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PE20001395A1 (es) | 2000-12-23 |
| CN1244327C (zh) | 2006-03-08 |
| DE19901687B4 (de) | 2006-06-01 |
| EP1020185B1 (de) | 2004-01-02 |
| HUP0000138A3 (en) | 2001-03-28 |
| DE59908195D1 (de) | 2004-02-05 |
| HUP0000138A2 (hu) | 2001-02-28 |
| EP1020185A2 (de) | 2000-07-19 |
| AU771064B2 (en) | 2004-03-11 |
| AU1011300A (en) | 2000-07-20 |
| ATE257012T1 (de) | 2004-01-15 |
| NZ502261A (en) | 2001-11-30 |
| HU0000138D0 (en) | 2000-03-28 |
| HK1029749A1 (en) | 2001-04-12 |
| AR022254A1 (es) | 2002-09-04 |
| SK642000A3 (en) | 2000-08-14 |
| PT1020185E (pt) | 2004-05-31 |
| ZA200000173B (en) | 2000-08-07 |
| RU2239417C2 (ru) | 2004-11-10 |
| SK285129B6 (sk) | 2006-07-07 |
| IL134076A (en) | 2005-05-17 |
| CA2295471A1 (en) | 2000-07-18 |
| IL134076A0 (en) | 2001-04-30 |
| DE19901687A1 (de) | 2000-07-20 |
| DK1020185T3 (da) | 2004-02-16 |
| EP1020185A3 (de) | 2000-09-27 |
| JP2000212072A (ja) | 2000-08-02 |
| CN1270029A (zh) | 2000-10-18 |
| PL337867A1 (en) | 2000-07-31 |
| US6685964B1 (en) | 2004-02-03 |
| KR20000071247A (ko) | 2000-11-25 |
| ES2213971T3 (es) | 2004-09-01 |
| CO5251462A1 (es) | 2003-02-28 |
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