MA31004B1 - Dispersion solide d'un antagoniste de la neurokinine - Google Patents

Dispersion solide d'un antagoniste de la neurokinine

Info

Publication number
MA31004B1
MA31004B1 MA32008A MA32008A MA31004B1 MA 31004 B1 MA31004 B1 MA 31004B1 MA 32008 A MA32008 A MA 32008A MA 32008 A MA32008 A MA 32008A MA 31004 B1 MA31004 B1 MA 31004B1
Authority
MA
Morocco
Prior art keywords
solid dispersion
functional
neurokinin antagonist
disorders
dyspepsy
Prior art date
Application number
MA32008A
Other languages
English (en)
Inventor
Anke Diederich
Carsten Timpe
Angelika Ries
Isabel Ottinger
Irene Mueller
Michael Herbig
Helmut Schuetz
Jay Parthiban Lakshman
Oskar Kalb
Original Assignee
Novartis Ag
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=37762542&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MA31004(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of MA31004B1 publication Critical patent/MA31004B1/fr

Links

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
    • A61K31/33—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
    • A61K31/4468—Non condensed piperidines, e.g. piperocaine having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K9/10—Dispersions; Emulsions
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
    • 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
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • 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
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • 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
    • A61P13/10—Drugs for disorders of the urinary system of the bladder

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Dispersion Chemistry (AREA)
  • Pulmonology (AREA)
  • Nutrition Science (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'INVENTION CONCERNE UNE DISPERSION SOLIDE COMPRENANT LE N-[(R)-EPSILON-CAPROLACTAM-3-YL]-AMIDE DE L'ACIDE (4R)-4-[N'-MÉTHYL-N'-(3,5-BISTRIFLUOROMÉTHYL-BENZOYL)-AMINO]-4-(3,4-DICHLOROBENZYL)-BUT-2-ÉNOÏQUE OU UN DE SES SELS PHARMACEUTIQUEMENT ACCEPTABLES OU UN DE SES SOLVATES ET UN VÉHICULE. DES COMPOSITIONS PHARMACEUTIQUES COMPRENANT UNE TELLE DISPERSION SOLIDE SONT UTILES POUR TRAITER LES PATIENTS SOUFFRANT DE TROUBLES FONCTIONNELS DE MOTILITÉ DES VISCÈRES, NOTAMMENT LE SYNDROME DU CÔLON IRRITABLE OU LA DYSPEPSIE FONCTIONNELLE, OU DES TROUBLES URINAIRES DE LA VESSIE, NOTAMMENT L'INCONTINENCE URINAIRE.
MA32008A 2006-12-22 2009-06-17 Dispersion solide d'un antagoniste de la neurokinine MA31004B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP06126964A EP1938804A1 (fr) 2006-12-22 2006-12-22 Préparation pharmaceutique comprenant un antagoniste de neurokinine

Publications (1)

Publication Number Publication Date
MA31004B1 true MA31004B1 (fr) 2009-12-01

Family

ID=37762542

Family Applications (1)

Application Number Title Priority Date Filing Date
MA32008A MA31004B1 (fr) 2006-12-22 2009-06-17 Dispersion solide d'un antagoniste de la neurokinine

Country Status (25)

Country Link
US (1) US20100015225A1 (fr)
EP (2) EP1938804A1 (fr)
JP (1) JP2010513356A (fr)
KR (1) KR20090092288A (fr)
CN (1) CN101541309A (fr)
AR (1) AR064622A1 (fr)
AU (1) AU2007338359B2 (fr)
BR (1) BRPI0720937A2 (fr)
CA (1) CA2672402A1 (fr)
CL (1) CL2007003767A1 (fr)
CO (1) CO6180497A2 (fr)
EA (1) EA200900827A1 (fr)
EC (1) ECSP099450A (fr)
GT (1) GT200900173A (fr)
IL (1) IL198780A0 (fr)
MA (1) MA31004B1 (fr)
MX (1) MX2009006747A (fr)
MY (1) MY145919A (fr)
NO (1) NO20092722L (fr)
NZ (1) NZ576987A (fr)
PE (1) PE20081848A1 (fr)
TN (1) TN2009000253A1 (fr)
TW (1) TW200848056A (fr)
WO (1) WO2008077591A2 (fr)
ZA (1) ZA200903271B (fr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW201309635A (zh) * 2006-02-10 2013-03-01 Dow Agrosciences Llc 殺蟲性之ｎ-取代（６-鹵烷基吡啶-３-基）烷基磺醯亞胺（二）
WO2010092925A1 (fr) * 2009-02-12 2010-08-19 あすか製薬株式会社 Dispersion solide, composition pharmaceutique comprenant celle-ci et procédés de production de la dispersion solide et de la composition pharmaceutique
JP5425229B2 (ja) * 2009-02-24 2014-02-26 ノバルティス アーゲー Ｎｋ受容体アンタゴニストの使用
US8263119B2 (en) * 2010-12-01 2012-09-11 Shire Llc Capsule formulations containing lanthanum compounds
ES2793148T3 (es) 2012-01-06 2020-11-13 Lundbeck La Jolla Research Center Inc Compuestos de carbamato y métodos para fabricarlos y usarlos
KR102055542B1 (ko) * 2015-03-10 2019-12-13 시오노기 잉크 고체 분산체
CA2984480A1 (fr) 2015-05-11 2016-11-17 Abide Therapeutics, Inc. Procedes de traitement de l'inflammation ou de la douleur neuropathique
CA2987867C (fr) 2015-06-09 2023-06-27 Capsugel Belgium Nv Formulations pour obtenir une dissolution rapide d'un medicament a partir de dispersions sechees par pulverisation dans des capsules
AU2017361254B2 (en) * 2016-11-16 2021-09-23 H. Lundbeck A/S. Pharmaceutical formulations
EP3541807B1 (fr) 2016-11-16 2021-09-29 H. Lundbeck A/S Une forme cristalline d'un inhibiteur de magl
CN115427403A (zh) 2020-04-21 2022-12-02 H.隆德贝克有限公司 单酰基甘油脂肪酶抑制剂的合成
CN111904960A (zh) * 2020-05-19 2020-11-10 合肥合源药业有限公司 一种固体分散体及药用组合物

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3622677A (en) * 1969-07-07 1971-11-23 Staley Mfg Co A E Compressed tablets containing compacted starch as binder-disintegrant ingredient
JPH054919A (ja) * 1990-07-25 1993-01-14 Sankyo Co Ltd チアゾリジン誘導体の固体分散体
MY132550A (en) * 1996-08-22 2007-10-31 Novartis Ag Acylaminoalkenylene-amide derivatives as nk1 and nk2 antogonists
PL340305A1 (en) * 1997-11-03 2001-01-29 Janssen Pharmaceutica Nv Composition of agents reducing the level of lipoides
KR100440553B1 (ko) * 1998-03-26 2004-07-15 후지사와 야꾸힝 고교 가부시키가이샤 서방성 제제
AR028253A1 (es) * 2000-03-16 2003-04-30 Pfizer Prod Inc Inhibidores de la glucogeno fosforilasa
JP2004131393A (ja) * 2002-10-08 2004-04-30 Kowa Co 易溶出性製剤
GB2394417A (en) * 2002-10-24 2004-04-28 Novartis Ag Solid dispersion comprising a piperidine substance P antagonist and a carrier
EP2158910A1 (fr) * 2003-10-27 2010-03-03 Novartis Ag Utilisation d'antagonistes de neurokinine dans le traitement de l'incontinence urinaire
GB0402679D0 (en) * 2004-02-06 2004-03-10 Novartis Ag Organic compounds
EP1871346A4 (fr) * 2005-04-20 2012-07-18 Ctc Bio Inc Composition pharmaceutique contenant une base exempte de sibutramine et son procede de conception
KR100627687B1 (ko) * 2005-04-20 2006-09-25 주식회사 씨티씨바이오 시부트라민 유리염기 함유 조성물 및 이의 제조방법

Also Published As

Publication number Publication date
GT200900173A (es) 2010-06-24
CO6180497A2 (es) 2010-07-19
NZ576987A (en) 2011-10-28
CN101541309A (zh) 2009-09-23
PE20081848A1 (es) 2009-01-19
US20100015225A1 (en) 2010-01-21
IL198780A0 (en) 2010-02-17
TN2009000253A1 (en) 2010-10-18
MY145919A (en) 2012-05-15
ECSP099450A (es) 2009-07-31
MX2009006747A (es) 2009-06-30
AR064622A1 (es) 2009-04-15
CA2672402A1 (fr) 2008-07-03
NO20092722L (no) 2009-07-21
AU2007338359A1 (en) 2008-07-03
EP2117511A2 (fr) 2009-11-18
KR20090092288A (ko) 2009-08-31
ZA200903271B (en) 2010-04-28
AU2007338359B2 (en) 2011-04-28
EP1938804A1 (fr) 2008-07-02
EA200900827A1 (ru) 2009-12-30
JP2010513356A (ja) 2010-04-30
TW200848056A (en) 2008-12-16
WO2008077591A2 (fr) 2008-07-03
WO2008077591A3 (fr) 2009-04-09
BRPI0720937A2 (pt) 2014-03-11
CL2007003767A1 (es) 2008-07-18

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