PE20011030A1 - Combinaciones farmaceuticas que comprenden tegaserod y omeprazol - Google Patents
Combinaciones farmaceuticas que comprenden tegaserod y omeprazolInfo
- Publication number
- PE20011030A1 PE20011030A1 PE2000001312A PE0013122000A PE20011030A1 PE 20011030 A1 PE20011030 A1 PE 20011030A1 PE 2000001312 A PE2000001312 A PE 2000001312A PE 0013122000 A PE0013122000 A PE 0013122000A PE 20011030 A1 PE20011030 A1 PE 20011030A1
- Authority
- PE
- Peru
- Prior art keywords
- alkyl
- halogen
- antagonists
- receptor
- anodycle
- Prior art date
Links
- IKBKZGMPCYNSLU-RGVLZGJSSA-N tegaserod Chemical compound C1=C(OC)C=C2C(/C=N/NC(=N)NCCCCC)=CNC2=C1 IKBKZGMPCYNSLU-RGVLZGJSSA-N 0.000 title abstract 2
- 229960002876 tegaserod Drugs 0.000 title abstract 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 title 1
- 229960000381 omeprazole Drugs 0.000 title 1
- 229910052736 halogen Inorganic materials 0.000 abstract 4
- 150000002367 halogens Chemical class 0.000 abstract 4
- 229940044551 receptor antagonist Drugs 0.000 abstract 3
- 239000002464 receptor antagonist Substances 0.000 abstract 3
- 108091005482 5-HT4 receptors Proteins 0.000 abstract 2
- 150000003973 alkyl amines Chemical class 0.000 abstract 2
- 239000003112 inhibitor Substances 0.000 abstract 2
- 108091005477 5-HT3 receptors Proteins 0.000 abstract 1
- 102000035037 5-HT3 receptors Human genes 0.000 abstract 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical class C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 abstract 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical class [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 abstract 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 abstract 1
- 229940127504 Somatostatin Receptor Agonists Drugs 0.000 abstract 1
- 230000003187 abdominal effect Effects 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000002496 gastric effect Effects 0.000 abstract 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 abstract 1
- SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 abstract 1
- 239000004031 partial agonist Substances 0.000 abstract 1
- 239000000018 receptor agonist Substances 0.000 abstract 1
- 229940044601 receptor agonist Drugs 0.000 abstract 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nutrition Science (AREA)
- Otolaryngology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US45838899A | 1999-12-10 | 1999-12-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PE20011030A1 true PE20011030A1 (es) | 2001-10-31 |
Family
ID=23820591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PE2000001312A PE20011030A1 (es) | 1999-12-10 | 2000-12-07 | Combinaciones farmaceuticas que comprenden tegaserod y omeprazol |
Country Status (30)
| Country | Link |
|---|---|
| EP (3) | EP1488788A1 (https=) |
| JP (1) | JP2003523324A (https=) |
| KR (1) | KR100765579B1 (https=) |
| CN (2) | CN1310644C (https=) |
| AR (1) | AR026916A1 (https=) |
| AT (1) | ATE293971T1 (https=) |
| AU (2) | AU778869B2 (https=) |
| BR (1) | BR0016275A (https=) |
| CA (1) | CA2388959A1 (https=) |
| CO (1) | CO5261535A1 (https=) |
| CZ (1) | CZ300690B6 (https=) |
| DE (1) | DE60019814T2 (https=) |
| DK (1) | DK1286668T3 (https=) |
| ES (1) | ES2240229T3 (https=) |
| HU (1) | HUP0301122A3 (https=) |
| IL (2) | IL149496A0 (https=) |
| MX (1) | MXPA02005695A (https=) |
| MY (1) | MY133423A (https=) |
| NO (1) | NO20022680L (https=) |
| NZ (2) | NZ531489A (https=) |
| PE (1) | PE20011030A1 (https=) |
| PL (1) | PL202201B1 (https=) |
| PT (1) | PT1286668E (https=) |
| RU (1) | RU2264215C2 (https=) |
| SG (1) | SG152025A1 (https=) |
| SK (1) | SK8062002A3 (https=) |
| TR (1) | TR200402293T2 (https=) |
| TW (1) | TWI263496B (https=) |
| WO (1) | WO2001041748A2 (https=) |
| ZA (1) | ZA200204493B (https=) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1284732A2 (en) * | 2000-05-18 | 2003-02-26 | Glaxo Group Limited | Method for treating functional dyspepsia using alosetron |
| GB0209481D0 (en) * | 2002-04-24 | 2002-06-05 | Novartis Ag | Organic compounds |
| JP2006516977A (ja) | 2003-01-13 | 2006-07-13 | ダイノゲン ファーマシューティカルズ，インコーポレイテッド | 悪心、嘔吐、レッチング、またはそれらの任意の組み合わせの治療方法 |
| GB0307440D0 (en) * | 2003-03-31 | 2003-05-07 | Novartis Ag | Organic compounds |
| WO2004105795A1 (en) * | 2003-05-27 | 2004-12-09 | Altana Pharma Ag | Pharmaceutical combinations of a proton pump inhibitor and a compound which modifies gastrointestinal motility |
| US20050090554A1 (en) * | 2003-09-12 | 2005-04-28 | John Devane | Treatment of gastroparesis and nonulcer dyspepsia with GABAB agonists |
| US7820690B2 (en) | 2004-03-19 | 2010-10-26 | Solvay Pharmaceuticals Gmbh | Method of treating or inhibiting a non-digestive tract derived abdominal disorder associated with pain using a 5-HT, receptor antagonist |
| AU2005261778A1 (en) * | 2004-07-14 | 2006-01-19 | Novartis Ag | Combination of DPP-IV inhibitors and compounds modulating 5-HT3 and/or 5-HT4 receptors |
| AU2006211205A1 (en) * | 2005-01-31 | 2006-08-10 | Novartis Ag | Organic compounds |
| GB0506800D0 (en) * | 2005-04-04 | 2005-05-11 | Merck Sharp & Dohme | New uses |
| US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
| US8679545B2 (en) | 2005-11-12 | 2014-03-25 | The Regents Of The University Of California | Topical corticosteroids for the treatment of inflammatory diseases of the gastrointestinal tract |
| US8324192B2 (en) | 2005-11-12 | 2012-12-04 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
| JP2009525269A (ja) | 2006-01-30 | 2009-07-09 | ユーロ−セルティーク エス．エイ． | カルシウムチャネルブロッカーとしての環状尿素化合物 |
| CN101466368A (zh) * | 2006-06-15 | 2009-06-24 | 诺瓦提斯公司 | 用于治疗或者预防胃损伤的仅包括替加色罗或者包括替加色罗与质子泵抑制剂组合的组合物 |
| CN101657436A (zh) | 2007-02-09 | 2010-02-24 | 特兰齐姆制药公司 | 大环生长素释放肽受体调节剂及其使用方法 |
| US8865692B2 (en) | 2007-11-13 | 2014-10-21 | Meritage Pharma, Inc | Compositions for the treatment of gastrointestinal inflammation |
| US20090149433A1 (en) | 2007-11-13 | 2009-06-11 | Meritage Pharma, Inc. | Compositions for the treatment of inflammation of the gastrointestinal tract |
| GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
| RU2769282C2 (ru) | 2016-06-20 | 2022-03-30 | Кимаб Лимитед | Анти-PD-L1 и IL-2 цитокины |
| US9567399B1 (en) | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
| WO2018029474A2 (en) | 2016-08-09 | 2018-02-15 | Kymab Limited | Anti-icos antibodies |
| US11858996B2 (en) | 2016-08-09 | 2024-01-02 | Kymab Limited | Anti-ICOS antibodies |
| EP3534947A1 (en) | 2016-11-03 | 2019-09-11 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses & methods |
| GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
| GB201721338D0 (en) | 2017-12-19 | 2018-01-31 | Kymab Ltd | Anti-icos Antibodies |
| EP3728314A1 (en) | 2017-12-19 | 2020-10-28 | Kymab Limited | Bispecific antibody for icos and pd-l1 |
| TW202313682A (zh) | 2021-05-18 | 2023-04-01 | 英商凱麥博有限公司 | 抗icos抗體之用途 |
| GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
| WO2023222854A1 (en) | 2022-05-18 | 2023-11-23 | Kymab Limited | Uses of anti-icos antibodies |
| FR3144752A1 (fr) | 2023-01-10 | 2024-07-12 | Song Huang | Utilisation de polysulfate de pentosane pour le traitement de la toux seche |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5362756A (en) * | 1989-02-20 | 1994-11-08 | Riviere Pierre J M | Use of fedotozine in the treatment of functional states of intestinal obstructions |
| HUT64023A (en) * | 1991-03-22 | 1993-11-29 | Sandoz Ag | Process for producing aminoguanidine derivatives and pharmaceutical compositions comprising such compounds |
| DE69226961T2 (de) * | 1991-12-21 | 1999-04-29 | Smithkline Beecham P.L.C., Brentford, Middlesex | Verwendung von 5-ht4 - antagonisten zur herstellung eines arzneimittels zur behandlung von harninkontinenz |
| GB9214184D0 (en) * | 1992-07-03 | 1992-08-12 | Smithkline Beecham Plc | Pharmaceuticals |
| US5932568A (en) * | 1994-11-21 | 1999-08-03 | Dainippon Pharmaceutical Co., Ltd. | 6-methoxy-1H-benzotriazole-5-carboxamide derivatives and pharmaceutical compositions containing them |
| US5919760A (en) * | 1996-04-12 | 1999-07-06 | Intensive Narcotic Detoxification Centers Of America, Llc | Method for treating acute and severe diarrhea |
| US6156771A (en) * | 1997-08-28 | 2000-12-05 | Rubin; Walter | Method for alleviation of lower gastrointestinal disorders in a human patient |
| GB9721139D0 (en) * | 1997-10-07 | 1997-12-03 | Glaxo Group Ltd | Medicaments |
-
2000
- 2000-11-20 TW TW089124545A patent/TWI263496B/zh not_active IP Right Cessation
- 2000-12-06 CO CO00093154A patent/CO5261535A1/es not_active Application Discontinuation
- 2000-12-07 AR ARP000106516A patent/AR026916A1/es unknown
- 2000-12-07 PE PE2000001312A patent/PE20011030A1/es not_active Application Discontinuation
- 2000-12-08 DE DE60019814T patent/DE60019814T2/de not_active Expired - Lifetime
- 2000-12-08 JP JP2001543093A patent/JP2003523324A/ja active Pending
- 2000-12-08 WO PCT/EP2000/012420 patent/WO2001041748A2/en not_active Ceased
- 2000-12-08 CN CNB008168814A patent/CN1310644C/zh not_active Expired - Fee Related
- 2000-12-08 CZ CZ20021967A patent/CZ300690B6/cs not_active IP Right Cessation
- 2000-12-08 PT PT00989967T patent/PT1286668E/pt unknown
- 2000-12-08 AU AU26728/01A patent/AU778869B2/en not_active Ceased
- 2000-12-08 TR TR2004/02293T patent/TR200402293T2/xx unknown
- 2000-12-08 EP EP04020247A patent/EP1488788A1/en not_active Withdrawn
- 2000-12-08 IL IL14949600A patent/IL149496A0/xx unknown
- 2000-12-08 EP EP00989967A patent/EP1286668B1/en not_active Expired - Lifetime
- 2000-12-08 MX MXPA02005695A patent/MXPA02005695A/es active IP Right Grant
- 2000-12-08 CN CNA2006100918377A patent/CN1875966A/zh active Pending
- 2000-12-08 RU RU2002118316/15A patent/RU2264215C2/ru not_active IP Right Cessation
- 2000-12-08 KR KR1020027007332A patent/KR100765579B1/ko not_active Expired - Fee Related
- 2000-12-08 MY MYPI20005769A patent/MY133423A/en unknown
- 2000-12-08 BR BR0016275-2A patent/BR0016275A/pt not_active Application Discontinuation
- 2000-12-08 HU HU0301122A patent/HUP0301122A3/hu unknown
- 2000-12-08 NZ NZ531489A patent/NZ531489A/en unknown
- 2000-12-08 CA CA002388959A patent/CA2388959A1/en not_active Abandoned
- 2000-12-08 NZ NZ566800A patent/NZ566800A/en unknown
- 2000-12-08 SG SG200404415-2A patent/SG152025A1/en unknown
- 2000-12-08 SK SK806-2002A patent/SK8062002A3/sk unknown
- 2000-12-08 ES ES00989967T patent/ES2240229T3/es not_active Expired - Lifetime
- 2000-12-08 AT AT00989967T patent/ATE293971T1/de not_active IP Right Cessation
- 2000-12-08 PL PL355663A patent/PL202201B1/pl not_active IP Right Cessation
- 2000-12-08 DK DK00989967T patent/DK1286668T3/da active
-
2002
- 2002-05-06 IL IL149496A patent/IL149496A/en not_active IP Right Cessation
- 2002-06-05 ZA ZA200204493A patent/ZA200204493B/xx unknown
- 2002-06-06 NO NO20022680A patent/NO20022680L/no not_active Application Discontinuation
-
2004
- 2004-08-26 EP EP07122308A patent/EP1913944A1/en not_active Withdrawn
-
2005
- 2005-02-22 AU AU2005200797A patent/AU2005200797B2/en not_active Ceased
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