BRPI0518760A8 - sal de potássio do composto, e, composição farmacêutica - Google Patents
sal de potássio do composto, e, composição farmacêuticaInfo
- Publication number
- BRPI0518760A8 BRPI0518760A8 BRPI0518760A BRPI0518760A BRPI0518760A8 BR PI0518760 A8 BRPI0518760 A8 BR PI0518760A8 BR PI0518760 A BRPI0518760 A BR PI0518760A BR PI0518760 A BRPI0518760 A BR PI0518760A BR PI0518760 A8 BRPI0518760 A8 BR PI0518760A8
- Authority
- BR
- Brazil
- Prior art keywords
- compound
- pharmaceutical composition
- potassium salt
- prophylaxis
- potassium
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 title abstract 2
- 238000011321 prophylaxis Methods 0.000 abstract 2
- 208000030507 AIDS Diseases 0.000 abstract 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 abstract 1
- 239000003084 hiv integrase inhibitor Substances 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 159000000001 potassium salts Chemical class 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 238000011282 treatment Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/12—[b,e]-condensed
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- AIDS & HIV (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63313204P | 2004-12-03 | 2004-12-03 | |
| PCT/US2005/043728 WO2006060712A2 (en) | 2004-12-03 | 2005-12-02 | Potassium salt of an hiv integrase inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| BRPI0518760A2 BRPI0518760A2 (pt) | 2008-12-09 |
| BRPI0518760A8 true BRPI0518760A8 (pt) | 2017-12-12 |
Family
ID=36171569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0518760A BRPI0518760A8 (pt) | 2004-12-03 | 2005-12-02 | sal de potássio do composto, e, composição farmacêutica |
Country Status (35)
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1725528T3 (da) | 2004-03-11 | 2013-09-02 | 4Sc Ag | Sulfonylpyrroler som hdac-inhibitorer |
| JP5228488B2 (ja) * | 2004-12-03 | 2013-07-03 | メルク・シャープ・アンド・ドーム・コーポレーション | 放出速度調節組成物を含有しているカルボキサミドhivインテグラーゼ阻害薬の医薬配合物 |
| MX2007006637A (es) * | 2004-12-03 | 2007-06-19 | Merck & Co Inc | Uso de atazanavir para mejorar los parametros farmacocineticos de farmacos metabolizados por isoforma 1a1 de udp-glucuronosil- transferasa. |
| TR201907729T4 (tr) * | 2004-12-03 | 2019-06-21 | Merck Sharp & Dohme | Bir anti-çekirdekleştirici ajan içeren farmasötik bileşim. |
| US20090087492A1 (en) * | 2006-03-14 | 2009-04-02 | Merck & Co., Inc. | Processes and Apparatuses for the Production of Crystalline Organic Microparticle Compositions by Micro-Milling and Crystallization on Micro-Seed and Their Use |
| EP2046328A4 (en) | 2006-07-19 | 2009-10-28 | Univ Georgia Res Found | PYRIDINONE DIKETOIC ACIDS: INHIBITORS OF HIV REPLICATION IN COMBINATION THERAPY |
| CA2702317A1 (en) * | 2007-07-09 | 2009-01-15 | Concert Pharmaceuticals, Inc. | Novel pyrimidinecarboxamide derivatives |
| CA2710987A1 (en) * | 2008-01-08 | 2009-07-16 | Merck Sharp & Dohme Corp. | Process for preparing n-substituted hydroxypyrimidinone carboxamides |
| ES2549387T3 (es) * | 2009-06-02 | 2015-10-27 | Hetero Research Foundation | Procedimiento de preparación de raltegravir potásico amorfo |
| WO2011024192A2 (en) | 2009-07-27 | 2011-03-03 | Matrix Laboratories Ltd | Novel polymorphs of raltegravir |
| ES2898348T3 (es) | 2009-10-26 | 2022-03-07 | Merck Sharp & Dohme | Composiciones farmacéuticas sólidas que contienen un inhibidor de la integrasa |
| DE102009056636A1 (de) | 2009-12-02 | 2011-06-09 | Ratiopharm Gmbh | Raltegravir-Polymorphe |
| MY172005A (en) | 2009-12-07 | 2019-11-11 | Univ Georgia | Pyridinone hydroxycyclopentyl carboxamides : hiv integrase inhibators with therapeutic applications |
| ES2362598B1 (es) * | 2009-12-17 | 2012-06-13 | Consejo Superior De Investigaciones Científicas (Csic) | Uso del raltegravir y derivados para la elaboración de medicamentos destinados al tratamiento de infecciones por herpesvirus. |
| CA2794952C (en) * | 2010-04-01 | 2018-05-15 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
| RU2012146517A (ru) | 2010-04-01 | 2014-05-10 | Тева Фармасьютикал Индастриз Лтд. | Соли ральтегравира и их кристаллические формы |
| EP2575465A4 (en) * | 2010-05-25 | 2013-11-20 | Hetero Research Foundation | Raltegravir SALTS |
| US9107922B2 (en) | 2010-07-16 | 2015-08-18 | Concert Pharmaceuticals, Inc. | Pyrimidinecarboxamide derivatives |
| CN101914067B (zh) * | 2010-08-26 | 2012-07-11 | 陈岱岭 | N-甲基嘧啶酮的合成方法 |
| JO3209B1 (ar) * | 2010-11-05 | 2018-03-08 | H Lundbeck As | طريقة لتصنيع نالتريكسون |
| WO2012103105A1 (en) | 2011-01-24 | 2012-08-02 | Assia Chemical Industries Ltd. | Processes for preparing raltegravir and intermediates in the processes |
| WO2012106534A2 (en) * | 2011-02-02 | 2012-08-09 | The Regents Of The University Of California | Hiv integrase inhibitors |
| EP2694497A1 (en) | 2011-04-06 | 2014-02-12 | Lupin Limited | Novel salts of raltegravir |
| CA2833006A1 (en) * | 2011-04-22 | 2012-10-26 | Merck Sharp & Dohme Corp. | Taste-masked formulations of raltegravir |
| US9968607B2 (en) | 2011-04-25 | 2018-05-15 | Hetero Research Foundation | Pharmaceutical compositions of raltegravir, methods of preparation and methods of use therof |
| EP2522665A1 (en) | 2011-05-03 | 2012-11-14 | Sandoz Ag | Crystalline sodium salt of an HIV integrase inhibitor |
| ES2450944T3 (es) | 2011-06-01 | 2014-03-25 | Ratiopharm Gmbh | Composición y comprimido que comprenden raltegravir |
| EP2755968A1 (de) | 2011-09-16 | 2014-07-23 | Hexal AG | Neue polymorphe form von raltegravir-kalium |
| CN103130788B (zh) * | 2011-11-24 | 2015-09-02 | 南开大学 | 嘧啶酰胺类化合物及其制备方法、抗hiv活性和抗tmv活性 |
| CN103130787B (zh) * | 2011-11-24 | 2015-06-10 | 南开大学 | 嘧啶酮酰胺类化合物及其制备方法、抗hiv活性和抗tmv活性 |
| EP2804607B1 (en) | 2011-12-26 | 2020-09-16 | Emcure Pharmaceuticals Limited | Synthesis of raltegravir |
| US20150328215A1 (en) | 2012-01-25 | 2015-11-19 | Lupin Limited | Stable amorphous raltegravir potassium premix and process for the preparation thereof |
| WO2014064711A2 (en) * | 2012-10-22 | 2014-05-01 | Hetero Research Foundation | Methods of administering raltegravir and raltegravir compositions |
| EP2818470A1 (en) | 2013-06-27 | 2014-12-31 | Basf Se | Cocrystals of raltegravir potassium |
| EP3022209B1 (en) | 2013-07-17 | 2018-03-07 | ratiopharm GmbH | Dolutegravir potassium salt |
| WO2015114608A1 (en) | 2014-02-03 | 2015-08-06 | Mylan Laboratories Ltd | Processes for the preparation of intermediates of raltegravir |
| EP3119773A1 (en) * | 2014-03-21 | 2017-01-25 | Mylan Laboratories Ltd. | A premix of crystalline raltegravir potassium salt and a process for the preparation thereof |
| US10257840B2 (en) | 2014-10-22 | 2019-04-09 | Telefonaktiebolaget Lm Ericsson (Publ) | Operation of wireless local area network in the presence of periodic interference |
| WO2016075605A1 (en) | 2014-11-10 | 2016-05-19 | Aurobindo Pharma Ltd | An improved process for the preparation of raltegravir |
| EP3472134B1 (en) * | 2016-06-21 | 2021-10-20 | Pharmathen S.A. | Process for preparing compounds useful as intermediates for the preparation of raltegravir |
| JP2019529410A (ja) * | 2016-09-15 | 2019-10-17 | ルピン・リミテッド | 純粋で安定な結晶のラルテグラビルカリウム3型の製造方法 |
| CN108610338A (zh) * | 2016-12-12 | 2018-10-02 | 天津国际生物医药联合研究院 | 一种嘧啶酮酰胺类化合物的制备方法 |
| ES2909302T3 (es) | 2017-11-14 | 2022-05-06 | Cambrex Profarmaco Milano S R L | Proceso para la preparación de Raltegravir |
| WO2019236395A1 (en) * | 2018-06-06 | 2019-12-12 | Merck Sharp & Dohme Corp. | Formulations of raltegravir |
| GB201907305D0 (en) * | 2019-05-23 | 2019-07-10 | Douglas Pharmaceuticals Ltd | Treatment of conditions |
| US12465565B2 (en) | 2020-01-23 | 2025-11-11 | Lupin Limited | Pharmaceutical compositions of raltegravir |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH624391A5 (enExample) * | 1976-12-14 | 1981-07-31 | Ciba Geigy Ag | |
| US5413999A (en) * | 1991-11-08 | 1995-05-09 | Merck & Co., Inc. | HIV protease inhibitors useful for the treatment of AIDS |
| US5717097A (en) * | 1991-11-08 | 1998-02-10 | Merck & Co., Inc. | HIV protease inhibitors useful for the treatment of AIDS |
| IL121789A (en) * | 1996-10-03 | 2001-06-14 | Rohm & Haas | A medicinal product for inhibiting mammalian cell tumors |
| PL348596A1 (en) * | 1998-12-25 | 2002-06-03 | Shionogi & Co | Aromatic heterocycle compounds having hiv integrase inhibiting activities |
| IT1318424B1 (it) * | 2000-03-24 | 2003-08-25 | Unihart Corp | Composti con attivita' anti-hiv. |
| ATE430745T1 (de) | 2000-10-12 | 2009-05-15 | Merck & Co Inc | Aza- und polyaza naphthalenyl karboxamide als inhibitoren der hiv-integrase |
| GB0028483D0 (en) * | 2000-11-22 | 2001-01-10 | Hoffmann La Roche | Hydroxyethylamine HIV protease inhibitors |
| DE60209381T2 (de) * | 2001-10-26 | 2006-10-05 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | N-substituierte hydroxypyrimidinoncarboxamid-hemmer der hiv-integrase |
| US7354932B2 (en) * | 2001-12-21 | 2008-04-08 | Anormed, Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| CN1596255A (zh) * | 2001-12-21 | 2005-03-16 | 阿诺麦德股份有限公司 | 具有强效的与趋化因子受体结合的杂环化合物 |
| WO2004046115A1 (ja) * | 2002-11-20 | 2004-06-03 | Japan Tobacco Inc. | 4−オキソキノリン化合物及びそのhivインテグラーゼ阻害剤としての利用 |
| BR0317749A (pt) * | 2002-12-27 | 2005-11-22 | Angeletti P Ist Richerche Bio | Composto, composição farmacêutica, e, uso de um composto |
| TW200423930A (en) * | 2003-02-18 | 2004-11-16 | Hoffmann La Roche | Non-nucleoside reverse transcriptase inhibitors |
| JP5228488B2 (ja) * | 2004-12-03 | 2013-07-03 | メルク・シャープ・アンド・ドーム・コーポレーション | 放出速度調節組成物を含有しているカルボキサミドhivインテグラーゼ阻害薬の医薬配合物 |
| MX2007006637A (es) | 2004-12-03 | 2007-06-19 | Merck & Co Inc | Uso de atazanavir para mejorar los parametros farmacocineticos de farmacos metabolizados por isoforma 1a1 de udp-glucuronosil- transferasa. |
| TR201907729T4 (tr) | 2004-12-03 | 2019-06-21 | Merck Sharp & Dohme | Bir anti-çekirdekleştirici ajan içeren farmasötik bileşim. |
-
2005
- 2005-02-12 UA UAA200707372A patent/UA87884C2/uk unknown
- 2005-11-24 AR ARP050104911A patent/AR052034A1/es not_active Application Discontinuation
- 2005-11-25 MY MYPI20055516A patent/MY144320A/en unknown
- 2005-11-25 TW TW094141625A patent/TWI344463B/zh not_active IP Right Cessation
- 2005-12-01 PE PE2005001398A patent/PE20061148A1/es not_active Application Discontinuation
- 2005-12-02 JP JP2007544570A patent/JP4705956B2/ja not_active Expired - Lifetime
- 2005-12-02 PL PL05852840T patent/PL1819700T3/pl unknown
- 2005-12-02 PT PT05852840T patent/PT1819700E/pt unknown
- 2005-12-02 CA CA2588398A patent/CA2588398C/en not_active Expired - Lifetime
- 2005-12-02 ME MEP-2012-21A patent/ME01985B/me unknown
- 2005-12-02 AU AU2005311671A patent/AU2005311671B8/en not_active Expired
- 2005-12-02 KR KR1020137028450A patent/KR20130122031A/ko not_active Withdrawn
- 2005-12-02 NZ NZ555376A patent/NZ555376A/en not_active IP Right Cessation
- 2005-12-02 BR BRPI0518760A patent/BRPI0518760A8/pt not_active Application Discontinuation
- 2005-12-02 CN CN2005800416393A patent/CN101068793B/zh not_active Expired - Lifetime
- 2005-12-02 US US11/293,678 patent/US7754731B2/en active Active
- 2005-12-02 DK DK05852840.7T patent/DK1819700T3/da active
- 2005-12-02 WO PCT/US2005/043781 patent/WO2006060730A2/en not_active Ceased
- 2005-12-02 MX MX2007006639A patent/MX2007006639A/es active IP Right Grant
- 2005-12-02 AT AT05852866T patent/ATE518844T1/de active
- 2005-12-02 RS RS20120021A patent/RS52197B/sr unknown
- 2005-12-02 EA EA200701204A patent/EA012418B1/ru not_active IP Right Cessation
- 2005-12-02 KR KR1020077015278A patent/KR101350420B1/ko not_active Expired - Lifetime
- 2005-12-02 EP EP05852866A patent/EP1819683B1/en not_active Expired - Lifetime
- 2005-12-02 WO PCT/US2005/043728 patent/WO2006060712A2/en not_active Ceased
- 2005-12-02 HR HR20120066T patent/HRP20120066T1/hr unknown
- 2005-12-02 GE GEAP200510157A patent/GEP20105086B/en unknown
- 2005-12-02 AT AT05852840T patent/ATE534645T1/de active
- 2005-12-02 SI SI200531435T patent/SI1819700T1/sl unknown
- 2005-12-02 ES ES05852866T patent/ES2370136T3/es not_active Expired - Lifetime
- 2005-12-02 EP EP05852840A patent/EP1819700B1/en not_active Expired - Lifetime
- 2005-12-02 ES ES05852840T patent/ES2375788T3/es not_active Expired - Lifetime
-
2007
- 2007-05-22 ZA ZA200704130A patent/ZA200704130B/xx unknown
- 2007-05-23 CR CR9146A patent/CR9146A/es not_active Application Discontinuation
- 2007-05-28 NI NI200700138A patent/NI200700138A/es unknown
- 2007-05-31 IL IL183614A patent/IL183614A/en active IP Right Grant
- 2007-06-01 TN TNP2007000215A patent/TNSN07215A1/fr unknown
- 2007-06-29 MA MA30041A patent/MA29120B1/fr unknown
- 2007-07-02 NO NO20073404A patent/NO338784B1/no unknown
-
2010
- 2010-06-04 US US12/793,801 patent/US8357798B2/en not_active Expired - Lifetime
-
2012
- 2012-02-21 CY CY20121100173T patent/CY1112859T1/el unknown
-
2014
- 2014-04-24 AR ARP140101707A patent/AR101429A2/es not_active Application Discontinuation
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