ATE458470T1 - Pharmazeutische zusammensetzungen aus einem polyethylenglykol mit einem molekulargewicht unter 600 dalton - Google Patents

Pharmazeutische zusammensetzungen aus einem polyethylenglykol mit einem molekulargewicht unter 600 dalton

Info

Publication number
ATE458470T1
ATE458470T1 AT05750655T AT05750655T ATE458470T1 AT E458470 T1 ATE458470 T1 AT E458470T1 AT 05750655 T AT05750655 T AT 05750655T AT 05750655 T AT05750655 T AT 05750655T AT E458470 T1 ATE458470 T1 AT E458470T1
Authority
AT
Austria
Prior art keywords
daltons
molecular weight
polyethylene glycol
pharmaceutical compositions
weight below
Prior art date
Application number
AT05750655T
Other languages
English (en)
Inventor
Olivier Lambert
Original Assignee
Novartis Pharma Gmbh
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=32732188&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ATE458470(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Pharma Gmbh filed Critical Novartis Pharma Gmbh
Application granted granted Critical
Publication of ATE458470T1 publication Critical patent/ATE458470T1/de

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61P1/12—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
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Inorganic Chemistry (AREA)
  • Obesity (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Neurosurgery (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Virology (AREA)
  • Urology & Nephrology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Emergency Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
AT05750655T 2004-06-09 2005-06-08 Pharmazeutische zusammensetzungen aus einem polyethylenglykol mit einem molekulargewicht unter 600 dalton ATE458470T1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0412866.6A GB0412866D0 (en) 2004-06-09 2004-06-09 Organic compounds
PCT/EP2005/006173 WO2005120453A1 (en) 2004-06-09 2005-06-08 Pharmaceutical compositions comprising polyethylene glycol having a molecular weight of less than 600 daltons

Publications (1)

Publication Number Publication Date
ATE458470T1 true ATE458470T1 (de) 2010-03-15

Family

ID=32732188

Family Applications (1)

Application Number Title Priority Date Filing Date
AT05750655T ATE458470T1 (de) 2004-06-09 2005-06-08 Pharmazeutische zusammensetzungen aus einem polyethylenglykol mit einem molekulargewicht unter 600 dalton

Country Status (20)

Country Link
US (4) US20080213330A1 (de)
EP (1) EP1758553B1 (de)
JP (1) JP5469810B2 (de)
KR (1) KR101259647B1 (de)
CN (1) CN100566756C (de)
AR (1) AR049295A1 (de)
AT (1) ATE458470T1 (de)
AU (1) AU2005251462B2 (de)
BR (1) BRPI0511966A (de)
CA (1) CA2567827C (de)
DE (1) DE602005019564D1 (de)
ES (1) ES2340693T3 (de)
GB (1) GB0412866D0 (de)
MX (1) MXPA06014420A (de)
PE (1) PE20060244A1 (de)
PL (1) PL1758553T3 (de)
PT (1) PT1758553E (de)
RU (1) RU2411031C2 (de)
TW (1) TW200610540A (de)
WO (1) WO2005120453A1 (de)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8658210B2 (en) 2006-04-17 2014-02-25 Advanced Cardiovascular Systems, Inc. Polyesteramide platform for site specific drug delivery
DE102006038240A1 (de) * 2006-08-07 2008-02-14 Biotronik Vi Patent Ag Verfahren zur Herstellung eines Komposits aus Oligo- oder Polynucleotiden und hydrophoben biodegradierbaren Polymeren sowie nach dem Verfahren erhaltenes Komposit
US8936780B2 (en) 2006-08-30 2015-01-20 Advanced Cardiovascular Systems, Inc. Stimuli responsive polyester amide particles
EP1917971A1 (de) * 2006-10-27 2008-05-07 Société de Conseils de Recherches et d'Applications Scientifiques ( S.C.R.A.S.) Zusammensetzungen mit verlängerter Wirkstofffreigabe, enthaltend Polymere mit sehr niedrigem Molekulargewicht
AU2008254538B2 (en) * 2007-05-18 2013-11-07 Durect Corporation Improved depot formulations
EP2296687A4 (de) * 2008-05-14 2012-12-26 Ipsen Pharma Sas Pharmazeutische zusammesetzungen von somatostatin-dopamin-konjugaten
CN102119022B (zh) * 2008-08-12 2015-09-09 诺华股份有限公司 药物组合物
EP2213307A1 (de) * 2009-02-03 2010-08-04 Novartis AG Injizierbare Depotformulierungen
WO2011060352A1 (en) * 2009-11-16 2011-05-19 Ipsen Pharma S.A.S. Pharmaceutical compositions of melanocortin receptor ligands
CA2792771A1 (en) * 2010-03-12 2011-09-15 Surmodics, Inc. Injectable drug delivery system
EP2547351B1 (de) * 2010-03-15 2016-04-27 Ipsen Pharma S.A.S. Pharmazeutische zusammensetzungen aus wachstumshormon-sekretagogen-rezeptorliganden
PL2701684T3 (pl) 2011-04-28 2018-09-28 Platform Brightworks Two, Ltd. Ulepszone preparaty pozajelitowe lipofilowych środków farmaceutycznych oraz sposoby ich wytwarzania i stosowania
WO2013131879A1 (en) 2012-03-07 2013-09-12 Novartis Ag New application for pasireotide
CN102633637A (zh) * 2012-03-30 2012-08-15 吉林大学 有效缓解和治疗便秘的药用配方
TWI523863B (zh) 2012-11-01 2016-03-01 艾普森藥品公司 體抑素－多巴胺嵌合體類似物
WO2014070965A2 (en) 2012-11-01 2014-05-08 Ipsen Pharma S.A.S Somatostatin analogs and dimers thereof
EP2986278A1 (de) 2013-03-11 2016-02-24 DURECT Corporation Injizierbare zusammensetzung mit gesteuerter freisetzung mit einem hochviskosen flüssigen träger
RU2541810C2 (ru) * 2013-05-23 2015-02-20 Закрытое Акционерное Общество "Фарм-Синтез" Способ лечения рака предстательной железы с использованием пролонгированной депо формы октреотида на фоне хирургической или медикаментозной кастрации
WO2015133580A1 (ja) * 2014-03-05 2015-09-11 わかもと製薬株式会社 注入可能なポリ乳酸類含有組成物
GB201519811D0 (en) * 2015-11-10 2015-12-23 Univ Belfast Ocular compositions
GB201522764D0 (en) * 2015-12-23 2016-02-03 Nucana Biomed Ltd Formulations of phosphate derivatives
CN107595765A (zh) * 2017-09-22 2018-01-19 沈阳兴齐眼药股份有限公司 一种眼用缓释药物递送系统及其制备方法
GB201816637D0 (en) 2018-10-12 2018-11-28 Heptares Therapeutics Ltd Selective somatostatin receptor agonists
CA3197170A1 (en) * 2020-09-30 2022-04-07 Tolmar International Limited Biodegradable polymer and solvent compositions and systems for extended storage and delivery of active pharmaceutical ingredients

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2209937B (en) * 1987-09-21 1991-07-03 Depiopharm S A Water insoluble polypeptides
IT1243390B (it) * 1990-11-22 1994-06-10 Vectorpharma Int Composizioni farmaceutiche in forma di particelle atte al rilascio controllato di sostanze farmacologicamente attive e procedimento per la loro preparazione.
US5980945A (en) * 1996-01-16 1999-11-09 Societe De Conseils De Recherches Et D'applications Scientifique S.A. Sustained release drug formulations
KR100416242B1 (ko) * 1999-12-22 2004-01-31 주식회사 삼양사 약물전달체용 생분해성 블록 공중합체의 액체 조성물 및이의 제조방법
GB0018891D0 (en) * 2000-08-01 2000-09-20 Novartis Ag Organic compounds
NZ523385A (en) * 2000-06-28 2005-09-30 Atul J Biodegradable vehicles and BAS-loaded delivery systems for use as biodegradable fillers and/or spacers, e.g. artificial skin
KR100446101B1 (ko) * 2000-12-07 2004-08-30 주식회사 삼양사 수난용성 약물의 서방성 제형 조성물
US20030049320A1 (en) * 2000-12-18 2003-03-13 Wockhardt Limited Novel in-situ forming controlled release microcarrier delivery system

Also Published As

Publication number Publication date
WO2005120453A1 (en) 2005-12-22
KR20070024575A (ko) 2007-03-02
CN1964698A (zh) 2007-05-16
KR101259647B1 (ko) 2013-04-30
AU2005251462B2 (en) 2009-07-09
US20080213330A1 (en) 2008-09-04
ES2340693T3 (es) 2010-06-08
PT1758553E (pt) 2010-05-06
EP1758553B1 (de) 2010-02-24
PL1758553T3 (pl) 2010-07-30
EP1758553A1 (de) 2007-03-07
GB0412866D0 (en) 2004-07-14
MXPA06014420A (es) 2007-02-19
TW200610540A (en) 2006-04-01
US20110301100A1 (en) 2011-12-08
PE20060244A1 (es) 2006-05-04
RU2006146610A (ru) 2008-07-20
DE602005019564D1 (de) 2010-04-08
US20140235555A1 (en) 2014-08-21
AU2005251462A1 (en) 2005-12-22
BRPI0511966A (pt) 2008-01-22
JP5469810B2 (ja) 2014-04-16
CA2567827C (en) 2013-02-12
AR049295A1 (es) 2006-07-12
JP2008501757A (ja) 2008-01-24
CA2567827A1 (en) 2005-12-22
CN100566756C (zh) 2009-12-09
US20130116178A1 (en) 2013-05-09
RU2411031C2 (ru) 2011-02-10

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