MA37693B1 - Composition pharmaceutique ayant une meilleure pulvérulence, agent médicamenteux, procédé de fabrication et application - Google Patents
Composition pharmaceutique ayant une meilleure pulvérulence, agent médicamenteux, procédé de fabrication et applicationInfo
- Publication number
- MA37693B1 MA37693B1 MA37693A MA37693A MA37693B1 MA 37693 B1 MA37693 B1 MA 37693B1 MA 37693 A MA37693 A MA 37693A MA 37693 A MA37693 A MA 37693A MA 37693 B1 MA37693 B1 MA 37693B1
- Authority
- MA
- Morocco
- Prior art keywords
- powderiness
- pharmaceutical composition
- improved
- composition
- manufacture
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 abstract 2
- 206010062016 Immunosuppression Diseases 0.000 abstract 1
- 206010042953 Systemic sclerosis Diseases 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 abstract 1
- 239000008280 blood Substances 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 239000000945 filler Substances 0.000 abstract 1
- 210000000987 immune system Anatomy 0.000 abstract 1
- 239000002955 immunomodulating agent Substances 0.000 abstract 1
- 230000002584 immunomodulator Effects 0.000 abstract 1
- 229940121354 immunomodulator Drugs 0.000 abstract 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract 1
- 210000004698 lymphocyte Anatomy 0.000 abstract 1
- 210000003563 lymphoid tissue Anatomy 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 239000008247 solid mixture Substances 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000009827 uniform distribution Methods 0.000 abstract 1
Classifications
-
- 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
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/4858—Organic compounds
-
- 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
- A61K31/137—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
- 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
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K9/2027—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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, 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
- A61K9/48—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
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- 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
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use
- A61J3/071—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use into the form of telescopically engaged two-piece capsules
- A61J3/074—Filling capsules; Related operations
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Transplantation (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- AIDS & HIV (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biophysics (AREA)
- Psychiatry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
L'invention se rapporte au domaine de la pharmaceutique et notamment des compositions pharmaceutiques solides comprenant du 2-amino-2-[2-(4-octylphényl)éthyl]propane-1,3-diol ou un sel pharmaceutiquement acceptable de celui-ci, une substance de glissement et une matière de charge ; l'invention concerne également des procédé de production de la composition pharmaceutique, des agents médicamenteux de suppression du système immunitaire et de traitement de la sclérose diffuse. Le 2-amino-2-[2-(4-octylphényl)éthyl]propane-1,3-diol consiste en un immuno-modulateur qui entraîne une redistribution des lymphocytes du flux sanguin dans les tissus lymphatiques secondaires, entraînant ainsi une immunosuppression. L'invention assure une répartition uniforme du composant actif dans la composition solide, une grande stabilité et une meilleure pulvérulence de la composition pharmaceutique. Grâce à cette meilleure pulvérulence, la composition de la présente invention peut être utilisée dans un équipement automatique.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2012129101/15A RU2496486C1 (ru) | 2012-07-11 | 2012-07-11 | Фармацевтическая композиция с улучшенной сыпучестью, лекарственное средство, способ получения и применение |
| PCT/RU2013/000572 WO2014011083A2 (fr) | 2012-07-11 | 2013-07-05 | Composition pharmaceutique ayant une meilleure pulvérulence, agent médicamenteux, procédé de fabrication et application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MA37693A1 MA37693A1 (fr) | 2016-06-30 |
| MA37693B1 true MA37693B1 (fr) | 2017-01-31 |
Family
ID=49446598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MA37693A MA37693B1 (fr) | 2012-07-11 | 2014-12-24 | Composition pharmaceutique ayant une meilleure pulvérulence, agent médicamenteux, procédé de fabrication et application |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9370576B2 (fr) |
| EP (1) | EP2873416B1 (fr) |
| JP (1) | JP6093015B2 (fr) |
| KR (1) | KR20150036228A (fr) |
| CN (1) | CN104487063B (fr) |
| AP (1) | AP2014008171A0 (fr) |
| BR (1) | BR112015000544A2 (fr) |
| CL (1) | CL2015000052A1 (fr) |
| CO (1) | CO7310521A2 (fr) |
| EA (1) | EA027712B1 (fr) |
| GE (1) | GEP201606571B (fr) |
| IL (1) | IL236562A0 (fr) |
| IN (1) | IN2015DN00130A (fr) |
| MA (1) | MA37693B1 (fr) |
| MX (1) | MX2015000467A (fr) |
| PE (1) | PE20150632A1 (fr) |
| RU (1) | RU2496486C1 (fr) |
| SG (1) | SG11201500178QA (fr) |
| TN (1) | TN2015000006A1 (fr) |
| UA (1) | UA113216C2 (fr) |
| WO (1) | WO2014011083A2 (fr) |
| ZA (1) | ZA201409481B (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140191896A1 (en) | 2013-01-10 | 2014-07-10 | Edh Us Llc | Ball spin rate measurement |
| RU2611415C1 (ru) * | 2015-11-17 | 2017-02-21 | Общество С Ограниченной Ответственностью "Валента - Интеллект" | ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, ОБЛАДАЮЩАЯ ТЕРАПЕВТИЧЕСКИМ ЭФФЕКТОМ В ОТНОШЕНИИ ДЕМИЕЛИНИЗИРУЮЩИХ ЗАБОЛЕВАНИЙ (Варианты) |
| WO2020005189A2 (fr) * | 2018-06-27 | 2020-01-02 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Compositions pharmaceutiques solides d'administration par voie orale comprenant du tériflunomide |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0155015B1 (ko) | 1992-10-21 | 1998-12-01 | 고우야 마사시 | 2-아미노-1,3-프로판디올 화합물 및 면역 억제제 |
| WO1997024112A1 (fr) | 1995-12-28 | 1997-07-10 | Yoshitomi Pharmaceutical Industries, Ltd. | Preparation a usage externe |
| US6476004B1 (en) | 1996-07-18 | 2002-11-05 | Mitsubishi Pharma Corporation | Pharmaceutical composition |
| GB9624038D0 (en) | 1996-11-19 | 1997-01-08 | Sandoz Ltd | Organic compounds |
| JPH1180026A (ja) | 1997-09-02 | 1999-03-23 | Yoshitomi Pharmaceut Ind Ltd | 新規免疫抑制剤、その使用方法およびその同定方法 |
| JP4627356B2 (ja) | 1999-06-30 | 2011-02-09 | 昭 松森 | ウイルス性心筋炎の予防または治療薬剤 |
| JP2002316985A (ja) | 2001-04-20 | 2002-10-31 | Sankyo Co Ltd | ベンゾチオフェン誘導体 |
| RU2358717C2 (ru) | 2002-05-16 | 2009-06-20 | Новартис Аг | Применение средств, связывающих edg-рецептор, в лечении ракового заболевания |
| CA2707750A1 (fr) * | 2003-04-08 | 2004-10-21 | Novartis Ag | Compositions pharmaceutiques solides contenant un antagoniste des recepteurs de la s1p et un alcool de sucre |
| WO2005025553A2 (fr) * | 2003-09-12 | 2005-03-24 | Neuronova Ab | Traitement de maladies ou de lesions du systeme nerveux avec le fty720 |
| PL1773307T3 (pl) | 2004-07-30 | 2015-03-31 | Novartis Ag | Preparaty 2-amino-1,3-propanodioli i ich analogów |
| GT200600350A (es) | 2005-08-09 | 2007-03-28 | Formulaciones líquidas | |
| MXPA05008573A (es) | 2005-08-12 | 2007-02-12 | Leopoldo Espinosa Abdala | Composicion de isoflavonas para tratamiento de los sintomas y trastornos fisiologicos de la menopausia. |
| EP1923058A1 (fr) * | 2006-09-26 | 2008-05-21 | Novartis AG | Composition pharmaceutique enrobée comprenant un agoniste ou un modulateur de S1P |
| RU2487703C2 (ru) * | 2006-09-26 | 2013-07-20 | Новартис Аг | Фармацевтические композиции, включающие модулятор s1р |
| WO2009048993A2 (fr) * | 2007-10-12 | 2009-04-16 | Novartis Ag | Compositions comprenant des modulateurs du récepteur de sphingosine 1-phosphate (s1p) |
| EP2560621A1 (fr) * | 2010-04-22 | 2013-02-27 | Ratiopharm GmbH | Fingolimod sous la forme de solution solide |
| US20130102683A1 (en) * | 2010-04-22 | 2013-04-25 | Ratiopharm Gmbh | Melt-granulated fingolimod |
-
2012
- 2012-07-11 RU RU2012129101/15A patent/RU2496486C1/ru active
-
2013
- 2013-05-07 UA UAA201500892A patent/UA113216C2/uk unknown
- 2013-07-05 KR KR1020157002215A patent/KR20150036228A/ko not_active Ceased
- 2013-07-05 AP AP2014008171A patent/AP2014008171A0/xx unknown
- 2013-07-05 PE PE2015000009A patent/PE20150632A1/es not_active Application Discontinuation
- 2013-07-05 MX MX2015000467A patent/MX2015000467A/es unknown
- 2013-07-05 BR BR112015000544A patent/BR112015000544A2/pt active Search and Examination
- 2013-07-05 SG SG11201500178QA patent/SG11201500178QA/en unknown
- 2013-07-05 JP JP2015521577A patent/JP6093015B2/ja not_active Expired - Fee Related
- 2013-07-05 EP EP13817392.7A patent/EP2873416B1/fr not_active Not-in-force
- 2013-07-05 EA EA201500096A patent/EA027712B1/ru not_active IP Right Cessation
- 2013-07-05 WO PCT/RU2013/000572 patent/WO2014011083A2/fr not_active Ceased
- 2013-07-05 CN CN201380036592.6A patent/CN104487063B/zh not_active Expired - Fee Related
- 2013-07-05 US US14/410,584 patent/US9370576B2/en not_active Expired - Fee Related
- 2013-07-05 GE GEAP201313729A patent/GEP201606571B/en unknown
-
2014
- 2014-12-22 ZA ZA2014/09481A patent/ZA201409481B/en unknown
- 2014-12-24 MA MA37693A patent/MA37693B1/fr unknown
-
2015
- 2015-01-01 IL IL236562A patent/IL236562A0/en unknown
- 2015-01-06 IN IN130DEN2015 patent/IN2015DN00130A/en unknown
- 2015-01-07 TN TNP2015000006A patent/TN2015000006A1/fr unknown
- 2015-01-08 CO CO15003855A patent/CO7310521A2/es unknown
- 2015-01-08 CL CL2015000052A patent/CL2015000052A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2873416B1 (fr) | 2017-04-26 |
| UA113216C2 (xx) | 2016-12-26 |
| JP6093015B2 (ja) | 2017-03-08 |
| MA37693A1 (fr) | 2016-06-30 |
| US20150335754A1 (en) | 2015-11-26 |
| PE20150632A1 (es) | 2015-05-20 |
| ZA201409481B (en) | 2016-02-24 |
| IL236562A0 (en) | 2015-02-26 |
| GEP201606571B (en) | 2016-11-10 |
| WO2014011083A3 (fr) | 2014-03-06 |
| AP2014008171A0 (en) | 2014-12-31 |
| KR20150036228A (ko) | 2015-04-07 |
| EP2873416A4 (fr) | 2016-03-16 |
| MX2015000467A (es) | 2015-06-05 |
| CN104487063A (zh) | 2015-04-01 |
| EA201500096A1 (ru) | 2015-05-29 |
| JP2015522068A (ja) | 2015-08-03 |
| SG11201500178QA (en) | 2015-03-30 |
| CN104487063B (zh) | 2017-05-10 |
| EA027712B1 (ru) | 2017-08-31 |
| CO7310521A2 (es) | 2015-06-30 |
| RU2496486C1 (ru) | 2013-10-27 |
| TN2015000006A1 (en) | 2016-06-29 |
| EP2873416A2 (fr) | 2015-05-20 |
| US9370576B2 (en) | 2016-06-21 |
| BR112015000544A2 (pt) | 2017-10-24 |
| WO2014011083A2 (fr) | 2014-01-16 |
| IN2015DN00130A (fr) | 2015-05-29 |
| CL2015000052A1 (es) | 2015-09-04 |
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