RU2018121633A - Фенфлураминовые композиции и способы их получения - Google Patents

Фенфлураминовые композиции и способы их получения Download PDF

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RU2018121633A
RU2018121633A RU2018121633A RU2018121633A RU2018121633A RU 2018121633 A RU2018121633 A RU 2018121633A RU 2018121633 A RU2018121633 A RU 2018121633A RU 2018121633 A RU2018121633 A RU 2018121633A RU 2018121633 A RU2018121633 A RU 2018121633A
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fenfluramine
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trifluoromethyl
phenyl
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Дерек ЛОНДЕБРО
Марк В. Андерсен
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Зодженикс Интернэшнл Лимитед
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Claims (41)

1. Способ получения фенфлураминового активного фармацевтического ингредиента, данный способ включает:
(a) гидролиз 2-(3-(трифторметил)фенил)ацетонитрильной композиции, чтобы получить композицию 2-(3-(трифторметил)фенил)уксусной кислоты;
(b) реакционное взаимодействие композиции 2-(3-(трифторметил)фенил)уксусной кислоты с уксусным ангидридом и катализатором, чтобы получить композицию 1-(3-(трифторметил)фенил)пропан-2-она; и
(c) восстановительное аминирование композиции 1-(3-(трифторметил)фенил)пропан-2-она этиламином при применении борогидридного восстановителя, чтобы получить фенфлураминовую композицию.
2. Способ по п. 1, где 2-(3-(трифторметил)фенил)ацетонитрильная композиция содержит по меньшей мере 0,2 масс.% трифторметил-фенильных региоизомеров.
3. Способ по п. 1, где 2-(3-(трифторметил)фенил)ацетонитрильную композицию получают из трифторметилбензола.
4. Способ по п. 1, дополнительно включающий, перед стадией (b), очистку композиции 2-(3-(трифторметил)фенил)уксусной кислоты, чтобы получить композицию, по существу не содержащую один или несколько трифторметил-фенильных региоизомеров и по существу не содержащую трифторметилбензальдегид и бензальдегид.
5. Способ по п. 4, где очистка включает кристаллизацию 2-(3-(трифторметил)фенил)уксусной кислоты из композиции.
6. Способ по п. 1, где стадия (b) включает очистку композиции 1-(3-(трифторметил)фенил)пропан-2-она кетоновым бисульфитным аддуктом.
7. Способ по п. 1, где стадия (b) включает селективное реакционное взаимодействие 2-(3-(трифторметил)фенил)уксусной кислоты в присутствии непрореагировавшей 2-(2-(трифторметил)фенил)уксусной кислоты.
8. Способ по п. 1, где стадия (b) дополнительно включает удаление непрореагировавшего региоизомера 2-(2-(трифторметил)фенил)уксусной кислоты из композиции 1-(3-(трифторметил)фенил)пропан-2-она.
9. Способ по п. 1, где фенфлураминовая композиция является исходной неочищенной и по существу не включает:
трифторметил-фенильные региоизомеры фенфлурамина или их соли;
металлические катализаторы;
растворители Класса I (ICH Q3C); и
спиртовый побочный продукт восстановления.
10. Способ по п. 1, где фенфлураминовая композиция является исходной неочищенной и содержит менее чем 1 масс.% суммарно трифторметил-фенильных региоизомеров фенфлурамина или их солей.
11. Способ по п. 1, где фенфлураминовая композиция является исходной неочищенной и имеет менее чем 10 масс.% спиртового побочного продукта восстановления.
12. Способ по п. 1, дополнительно включающий кристаллизацию фенфлурамина или его соли из фенфлураминовой композиции.
13. Способ по п. 1, где стадию (b) выполняют при условиях, которые включают приведение композиции 2-(3-(трифторметил)фенил)уксусной кислоты в контактирование с примерно 0,5 эквивалента 1-метилимидазола и примерно 5 эквивалентами или более уксусного ангидрида, в необязательном растворителе.
14. Способ по п. 1, где стадию (c) выполняют при условиях, которые включают контактирование композиции 1-(3-(трифторметил)фенил)пропан-2-она с раствором 70 масс.% этиламина в воде и примерно 2,25 эквивалента или более триацетоксиборогидрида в метаноле в качестве растворителя.
15. Способ по п. 1, где фенфлураминовая композиция имеет следующий профиль:
по меньшей мере 80 масс.% фенфлурамина или его соли;
менее чем 1 масс.% 2-фенфлурамина или его соли;
менее чем 1 масс.% 4-фенфлурамина или его соли; и
менее чем 10 масс.% спиртового побочного продукта восстановления фенфлурамина.
16. Способ по п. 1, дополнительно включающий:
преобразование фенфлурамина в фенфлураминовой композиции в фармацевтически приемлемую соль фенфлурамина;
кристаллизацию фармацевтически приемлемой соли фенфлурамина из фенфлураминовой композиции; где фармацевтически приемлемая соль фенфлурамина имеет следующий профиль чистоты:
по меньшей мере 90% или более фармацевтически приемлемой соли фенфлурамина;
менее чем 1 масс.% 2-фенфлурамина;
менее чем 5 масс.% 4-фенфлурамина; и
менее чем 5 масс.% спиртового побочного продукта восстановления фенфлурамина.
17. Способ по п. 1, дополнительно включающий очистку свободного основания фенфлурамина из фенфлураминовой композиции.
18. Способ по п. 1, дополнительно включающий выполнение хирального разделения рацемической фенфлураминовой композиции, чтобы получить нерацемическую фенфлураминовую композицию, содержащую доминирующий стереоизомер фенфлурамина.
19. Фенфлураминовый активный фармацевтический ингредиент, содержащий фармацевтически приемлемую соль фенфлурамина и имеющий менее чем 0,2 масс.% суммарно трифторметильных региоизомеров.
20. Фенфлураминовый активный фармацевтический ингредиент по п. 19, имеющий следующий профиль:
по меньшей мере 90% или по массе фармацевтически приемлемой соли фенфлурамина;
менее чем 0,2 масс.% 2-фенфлурамина;
менее чем 0,2 масс.% 4-фенфлурамина; и
менее чем 1 масс.% фенфлураминового спирта.
RU2018121633A 2015-12-22 2016-12-20 Фенфлураминовые композиции и способы их получения RU2731179C2 (ru)

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Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9549909B2 (en) 2013-05-03 2017-01-24 The Katholieke Universiteit Leuven Method for the treatment of dravet syndrome
WO2017112701A1 (en) 2015-12-22 2017-06-29 Zogenix International Limited Metabolism resistant fenfluramine analogs and methods of using the same
JP6893213B2 (ja) * 2015-12-22 2021-06-23 ゾゲニクス インターナショナル リミテッド フェンフルラミン組成物およびその調製法
RU2746000C2 (ru) 2016-08-24 2021-04-05 Зодженикс Интернэшнл Лимитед Состав для ингибирования образования агонистов 5-ht2b и способы его применения
US10682317B2 (en) * 2017-09-26 2020-06-16 Zogenix International Limited Ketogenic diet compatible fenfluramine formulation
WO2019067413A1 (en) 2017-09-26 2019-04-04 Zogenix International Limited USE OF A FENFLURAMINE FORMULATION TO REDUCE THE NUMBER AND FREQUENCIES OF CONVULSIVE CRISES IN PATIENT POPULATIONS
US11571397B2 (en) 2018-05-11 2023-02-07 Zogenix International Limited Compositions and methods for treating seizure-induced sudden death
WO2019241005A1 (en) 2018-06-14 2019-12-19 Zogenix International Limited Compositions and methods for treating respiratory depression with fenfluramine
WO2020105005A1 (en) 2018-11-19 2020-05-28 Zogenix International Limited Methods of treating rett syndrome using fenfluramine
US20210401776A1 (en) * 2018-11-30 2021-12-30 Zogenix International Limited Method of treating refractory epilepsy syndromes using fenfluramine enantiomers
JP2022548892A (ja) 2019-09-17 2022-11-22 ゾゲニクス インターナショナル リミテッド てんかん患者をフェンフルラミンで治療する方法
WO2021117057A1 (en) * 2019-12-10 2021-06-17 Maithri Drugs Pvt Ltd Polymorph of n-ethyl-1-(3-(trifluoromethyl)phenyl)propan-2-amine hydrochloride and process for preparation thereof
US11612574B2 (en) 2020-07-17 2023-03-28 Zogenix International Limited Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
WO2023037182A2 (en) * 2021-08-19 2023-03-16 Biophore India Pharmaceuticals Pvt Ltd AN IMPROVED PROCESS FOR THE PREPARATION OF N-ETHYL- α -METHYL-3-(TRIFLUOROMETHYL)PHENETHYLAMINE HYDROCHLORIDE

Family Cites Families (143)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL270984A (ru) 1960-11-05
US3117160A (en) 1961-07-27 1964-01-07 Pfizer & Co C Aralkylamines
US3198834A (en) * 1964-07-27 1965-08-03 Snc Science Union Et Compagnie Optical isomers of trifluoromethylated phenethylamines
GB1254332A (en) 1969-02-27 1971-11-17 Science Union & Cie Amino acids and their derivatives and processes for preparing them
DE2143204C3 (de) 1971-08-28 1979-09-27 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler, 6000 Frankfurt N-Fluoralkyl-phenylisopropylamin-Derivate und deren Salze, Verfahren zu deren Herstellung und Arzneimittel auf deren Basis
DE2150399A1 (de) 1971-10-09 1973-04-12 Hoechst Ag Neue oxime
GB1413070A (en) 1973-07-27 1975-11-05 Beecham Group Ltd Process for the production of - norfenfluramine and - fenfluramine and salts thereof
GB1413078A (en) 1973-07-27 1975-11-05 Beecham Group Ltd Process for the production of plus-norfenfluramine and plus-fenfluramine and salts thereof
JPS54144347A (en) * 1978-05-02 1979-11-10 Nikken Kagaku Kk 3-(2-fluoro-4-biphenylyl)-2-butanone
US4452815A (en) 1980-06-16 1984-06-05 Massachusetts Institute Of Technology Method of utilizing d,l-fenfluramine for modifying feeding behavior
US4309445A (en) * 1980-06-16 1982-01-05 Massachusetts Institute Of Technology d-Fenfluramine for modifying feeding behavior
US4721823A (en) * 1986-09-19 1988-01-26 Pennzoil Products Company Lubricants comprising novel cyclopentanes, cyclopentadienes, cyclopentenes, and mixtures thereof and methods of manufacture
DE3717434C1 (de) 1987-05-23 1988-09-15 Degussa Verfahren zur Herstellung von m-Trifluormethylphenylacetonitril
KR890003368A (ko) * 1987-08-06 1989-04-14 원본미기재 특정의 치환된 페닐알킬아미노(및 아미노산) 유도체 및 기타 세로토닌농도 저하제로 오심 및 구토를 치료하는 방법
US4857533A (en) 1988-12-15 1989-08-15 Baker Cummins Pharmaceuticals, Inc. Method of treatment for autoimmune diseases
HU204497B (en) 1989-10-09 1992-01-28 Chinoin Gyogyszer Es Vegyeszet Process for producing phenfluramine
IT1238686B (it) * 1990-02-09 1993-09-01 Lab Mag Spa Procedimento per la preparazione di levo e destro fenfluramina
FR2684552B1 (fr) 1991-12-06 1995-04-28 Adir Utilisation de la d-fenfluramine et de derives de la fenfluramine dans le traitement de l'hypertension chez des sujets insulino-resistants.
US5985880A (en) 1996-06-05 1999-11-16 Delta Pharmaceuticals Compositions and methods for reducing respiratory depression and attendant side effects of mu opioid compounds
AU7513494A (en) 1993-08-06 1995-02-28 Upjohn Company, The 2-aminoindans as selective dopamine d3 ligands
US5834477A (en) 1993-12-08 1998-11-10 The United States Of America As Represented By The Secretary Of The Army Opiate analgesic formulation with improved safety
US5412102A (en) 1994-05-27 1995-05-02 Syntex (U.S.A.) Inc. Processes for preparing 1-butyl-2-[2'-(2H-tetrazol-5-yl) biphenyl-4-ylmethyl]-1H-indole-3-carboxylic acid
ATE199829T1 (de) 1994-06-03 2001-04-15 Thejmde Trust Meta substituierte arylalkylamine und therapeutische und diagnostische verwendung davon
IT1298349B1 (it) 1996-05-29 2000-01-05 Alfa Chem Ital Processo per la produzione di 1 - (3-trifluorometil) fenil-propan- 2-one intermedio nella sintesi della fenfluramina
IT1292885B1 (it) * 1997-04-28 1999-02-11 Alfa Chem Ital Processo per la produzione degli isomeri (r) ed (s)- alfa -metil-3- (trifluorometil)benzene-etanamina.
EP0920864A1 (en) 1997-12-03 1999-06-09 Pfizer Products Inc. Combination therapy including a specific beta-3 agonist and an anorectic agent
US20020098175A1 (en) 1998-06-16 2002-07-25 Zohoungbogbo Mathias C. Dietetic food composition and dietetic method using such composition
US6045501A (en) 1998-08-28 2000-04-04 Celgene Corporation Methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug
WO2000038672A2 (en) 1998-12-23 2000-07-06 Orphan Medical, Inc. Microbiologically sound and stable solutions of gamma-hydroxybutyrate salt for the treatment of narcolepsy
US20080103179A1 (en) 2006-10-27 2008-05-01 Tam Peter Y Combination Therapy
US7124031B1 (en) 2000-05-11 2006-10-17 Medco Health Solutions, Inc. System for monitoring regulation of pharmaceuticals from data structure of medical and labortory records
WO2002006826A1 (en) 2000-07-17 2002-01-24 Opt-E-Scrip, Inc. Single-patient drug trials used with accumulated database
US6315720B1 (en) 2000-10-23 2001-11-13 Celgene Corporation Methods for delivering a drug to a patient while avoiding the occurrence of an adverse side effect known or suspected of being caused by the drug
US7585493B2 (en) * 2001-05-24 2009-09-08 Alexza Pharmaceuticals, Inc. Thin-film drug delivery article and method of use
JP2005503425A (ja) * 2001-05-24 2005-02-03 アレックザ モレキュラー デリヴァリー コーポレイション 所定の吸入ルートによる薬剤エステルの送出
CA2449613A1 (en) 2001-06-22 2003-01-03 Universite Catholique De Louvain Hydrogel beads or capsules as artificial media for insects oviposition and rearing of endoparasitoids
MXPA04001026A (es) 2001-07-31 2005-06-20 Wyeth Corp Formulacion de sucralosa para disimular sabores desagradables.
AUPR732601A0 (en) 2001-08-28 2001-09-20 Polychip Pharmaceuticals Pty Ltd Methods for the synthesis of amines such as ephedrine and inter mediates
IL160983A0 (en) 2001-09-24 2004-08-31 Imp College Innovations Ltd Use of pyy for preparation of a medicament for modification of feeding behavior
RU2317104C2 (ru) * 2001-09-24 2008-02-20 Импиэриэл Инноувейшнс Лимитид Способ модификации пищевого поведения и применение pyy или его агониста в качестве средства для модификации пищевого поведения
US6599901B1 (en) 2001-11-19 2003-07-29 Hoffman-La Roche Inc. Pyridone substituted benzothiazole derivatives
US7101572B2 (en) 2001-12-07 2006-09-05 Unilab Pharmatech, Ltd. Taste masked aqueous liquid pharmaceutical composition
NZ534757A (en) 2002-03-12 2006-07-28 Merck & Co Inc Substituted amides
CA2479744A1 (en) 2002-03-28 2003-10-09 Paul E. Finke Substituted 2,3-diphenyl pyridines
US7668730B2 (en) 2002-12-17 2010-02-23 JPI Commercial, LLC. Sensitive drug distribution system and method
WO2005004865A1 (en) 2003-07-08 2005-01-20 Georg-August-Universität Göttingen Use of 5-ht4(a)-serotonin receptor agonists
GB0410266D0 (en) 2004-05-07 2004-06-09 Ketocytonyx Inc Treatment of apoptosis
US20050260610A1 (en) 2004-05-20 2005-11-24 Kurtz Richard E Method for diagnosing and prescribing a regimen of therapy for human health risk
US9820658B2 (en) 2006-06-30 2017-11-21 Bao Q. Tran Systems and methods for providing interoperability among healthcare devices
JP2008536545A (ja) 2005-03-21 2008-09-11 ヘルス−スマート リミテッド 連続血圧モニタリングのためのシステム
RU2007148444A (ru) 2005-05-25 2009-06-27 Янссен Фармацевтика Н.В. (Be) Педиатрическая композиция топирамата
JP2008546376A (ja) 2005-06-16 2008-12-25 バイオノミックス リミテッド Ｓｃｎ１ａ遺伝子における変異を検出することによっててんかんを診断および処置するための方法
GB0515090D0 (en) 2005-07-22 2005-08-31 Birmingham Res & Dev Ltd Novel epilepsy treatment
US9125900B2 (en) 2005-09-14 2015-09-08 University Of The Witwatersrand, Johannesburg Pharmaceutical composition
US8109891B2 (en) 2005-09-19 2012-02-07 Biolert Ltd Device and method for detecting an epileptic event
CA2630604C (en) 2005-11-29 2016-01-19 Children's Hospital Medical Center Optimization and individualization of medication selection and dosing
US7592461B2 (en) 2005-12-21 2009-09-22 Bristol-Myers Squibb Company Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
WO2007079181A2 (en) 2005-12-28 2007-07-12 Neurovista Corporation Methods and systems for recommending an action to a patient for managing epilepsy and other neurological disorders
AU2007213069B2 (en) 2006-02-06 2010-12-23 Novartis Ag Combination of organic compounds
AR061311A1 (es) 2006-06-08 2008-08-20 Medichem Sa Procesos para preparar clorhidrato de cinacalcet y formas polimorficas del mismo
DE102006030113B4 (de) 2006-06-28 2009-02-12 Chemische Fabrik Budenheim Kg Graphitfreier Hochtemperatur-Schmierstoff
CN101600436A (zh) 2006-08-31 2009-12-09 艾伯塔大学校董 使用正变构ampa受体调节剂抑制呼吸抑制的方法
EP2115540A4 (en) 2007-01-31 2011-02-02 Quintiles Transnat Corp Inc METHOD AND SYSTEMS FOR ASSIGNING REPRESENTATIVE ELEMENTS TO LOCATIONS IN CLINICAL ATTEMPTS
HUE032251T2 (en) 2007-02-08 2017-09-28 Biogen Ma Inc Neuroprotection in demyelinating diseases
JP2010520162A (ja) * 2007-02-28 2010-06-10 スミスクライン ビーチャム コーポレーション ステアロイル−ＣｏＡデサチュラーゼ阻害剤であるチアジアゾール誘導体
GB2456183A (en) 2008-01-04 2009-07-08 Gw Pharma Ltd Anti-psychotic composition comprising cannabinoids and anti-psychotic medicament
ES2620672T3 (es) 2008-01-09 2017-06-29 Charleston Laboratories, Inc. Comprimidos de doble capa que comprenden oxicodona y prometazina
US20110207718A1 (en) 2008-08-06 2011-08-25 Gosforth Centre (Holdings) Pty Ltd. Compositions and methods for treating psychiatric disorders
WO2010020585A1 (en) 2008-08-18 2010-02-25 INSERM (Institut National de la Santé et de la Recherche Médicale) Serotonin reuptake inhibitors for the treatment of rett syndrome
MX2011002339A (es) 2008-09-05 2011-04-04 Gruenenthal Gmbh Combinacion farmaceutica de 3-(3-dimetilamino-1-etil-2-metil-propi l)-fenol y un antiepileptico.
US8664442B2 (en) 2008-09-09 2014-03-04 Chemtura Corporation Anti-oxidants
US8386274B1 (en) 2008-09-17 2013-02-26 Mckesson Financial Holdings Limited Systems and methods for a prescription safety network utilizing eligibility verification transactions
BRPI0919796A2 (pt) 2008-10-09 2015-12-15 Acraf formulação farmacêutica líquida livre de açúcar, e, excipiente líquido livre de açucar farmaceuticamente aceitável
US20110230473A1 (en) 2008-10-10 2011-09-22 Gordon Richard K Methods and Compositions for Treating Status Epilepticus and Seizures Causing Status Epilepticus
TWI424832B (zh) 2008-12-15 2014-02-01 Proteus Digital Health Inc 與身體有關的接收器及其方法
EP2406765A4 (en) 2009-03-09 2014-12-31 Celgene Corp DEVICE FOR ADMINISTERING A MEDICAMENT TO A PATIENT WITH RESTRICTED PATIENT-SIDED ACCESS TO THE MEDICAMENT IN THE CASE OF CONTRAINDICATIONS AND APPLICATION METHOD THEREFOR
EP2419400A1 (en) 2009-04-15 2012-02-22 Research Triangle Institute Monoamine reuptake inhibitors
US20100324936A1 (en) 2009-04-22 2010-12-23 Suresh-Kumar Venkata Vishnubhatla Pharmacy management and administration with bedside real-time medical event data collection
US9453027B2 (en) 2009-07-27 2016-09-27 Daljit Singh Dhanoa Deuterium-enriched pyridinonecarboxamides and derivatives
WO2011085181A1 (en) 2010-01-08 2011-07-14 Eurand, Inc. Taste masked topiramate composition and an orally disintegrating tablet comprising the same
EP2545522B1 (en) 2010-03-09 2017-07-26 Perceptimed, Inc. Medication verification and dispensing
WO2011119227A2 (en) 2010-03-25 2011-09-29 Columbia Northwest Pharmaceuticals, Llc Compositions for the treatment of central nervous system disorders including depression employing novel drug combination therapy to reduce suicidality in patients
JP2011221623A (ja) 2010-04-06 2011-11-04 Kakimori Suri 在宅診療支援システム及び方法
JP2013526583A (ja) 2010-05-21 2013-06-24 リサーチ・トライアングル・インスティチュート フェニルモルホリンおよびその類似体
EP2399513B1 (en) 2010-06-23 2017-01-04 Qatar University Qstp-B System for non-invasive automated monitoring, detection, analysis, characterisation, prediction or prevention of seizures and movement disorder symptoms
EP2598159A4 (en) 2010-07-30 2014-01-08 Merck Sharp & Dohme INHIBITION OF CYP3A METABOLISM OF THE MEDICINAL PRODUCT
KR20180118801A (ko) 2010-09-01 2018-10-31 에자이 알앤드디 매니지먼트 가부시키가이샤 체중 관리에 유용한 5-ｈｔ2ｃ 작동제의 변형-방출 투여 형태
US20120270848A1 (en) 2010-10-22 2012-10-25 Galleon Pharmaceuticals, Inc. Novel Compositions and Therapeutic Methods Using Same
AU2011322147A1 (en) 2010-10-26 2013-04-18 Alpharma Pharmaceuticals, Llc Formulations and methods for attenuating respiratory depression induced by opioid overdose
RU103209U1 (ru) 2010-10-29 2011-03-27 Общество С Ограниченной Ответственностью "Правовое Сопровождение Бизнеса" Клиническая информационная система
GB2487712B (en) 2011-01-04 2015-10-28 Otsuka Pharma Co Ltd Use of the phytocannabinoid cannabidiol (CBD) in combination with a standard anti-epileptic drug (SAED) in the treatment of epilepsy
JP5693325B2 (ja) 2011-03-29 2015-04-01 小林クリエイト株式会社 健診結果出力システム及び健診結果出力プログラム
GB201111712D0 (en) 2011-07-08 2011-08-24 Gosforth Ct Holdings Pty Ltd Pharmaceutical compositions
WO2013096878A1 (en) 2011-12-22 2013-06-27 University Of Idaho Garcinia buchananii baker compounds, compositions and related methods
US9346798B2 (en) 2012-02-13 2016-05-24 Amgen Inc. Dihydrobenzoxazine and tetrahydroquinoxaline sodium channel inhibitors
US20130218586A1 (en) 2012-02-21 2013-08-22 Frederic J. Huser Methods and elements for identifying the appropriate patient populations who can safely use prescription chronic care drugs that are switched to an over-the-counter regulatory status
JP6075973B2 (ja) 2012-06-04 2017-02-08 富士通株式会社 健康状態判定装置およびその作動方法
MX2015006120A (es) 2012-11-15 2016-02-05 Galleon Pharmaceuticals Inc Compuestos novedosos oralmente biodisponibles que modulan el control de la respiracion, y metodos de uso de los mismos.
WO2014106825A2 (en) 2013-01-06 2014-07-10 Jonathan Rabinowitz Methods and devices for identifying improper medical reporting
US9549909B2 (en) 2013-05-03 2017-01-24 The Katholieke Universiteit Leuven Method for the treatment of dravet syndrome
CN103342648A (zh) 2013-07-22 2013-10-09 北京科莱博医药开发有限责任公司 瑞替加滨中间体的制备方法和瑞替加滨的制备方法
WO2015026849A1 (en) 2013-08-19 2015-02-26 The Regents Of The University Of California Compounds and methods for treating an epileptic disorder
WO2015066344A1 (en) 2013-11-01 2015-05-07 Arena Pharmaceuticals, Inc. 5-ht2c receptor agonists and compositions and methods of use
WO2015077057A1 (en) 2013-11-20 2015-05-28 Texas Southern University Methionine aminopeptidase inhibitors for treating infectious diseases
CN103886415A (zh) 2014-03-25 2014-06-25 北京蝶禾谊安信息技术有限公司 药品管理方法和装置
GB2530001B (en) 2014-06-17 2019-01-16 Gw Pharma Ltd Use of cannabidiol in the reduction of convulsive seizure frequency in treatment-resistant epilepsy
JP6466116B2 (ja) 2014-09-12 2019-02-06 株式会社東芝 運行制御システム
AU2015326472B2 (en) 2014-09-29 2020-05-28 Zogenix International Limited Control system for control of distribution of medication
EP3253418A1 (en) 2015-02-06 2017-12-13 Marinus Pharmaceuticals, Inc. Intravenous ganaxolone formulations and their use in treating status epilepticus and other seizure disorders
CA2977135C (en) 2015-02-25 2023-08-22 The Regents Of The University Of California 5ht agonists for treating disorders
US10292996B2 (en) 2015-03-26 2019-05-21 The Trustees Of Columbia University In The City Of New York Deoxyribonucleoside monophospate bypass therapy for mitochondrial DNA depletion syndrome
JP6668045B2 (ja) 2015-05-15 2020-03-18 ゾゲニクス インターナショナル リミテッド ドラベ症候群を処置するための選択的５−ｈｔ受容体アゴニストおよびアンタゴニスト
SI3310362T1 (sl) 2015-06-17 2020-02-28 The Trustees Of Columbia University In The City Of New York, Deoksinukleozidna terapija za bolezni, povzročene z neuravnoteženimi nabori nukleotidov, vključno s sindromom pomanjkanja mitohondrijske DNA
KR102207539B1 (ko) 2015-06-30 2021-01-26 네우라드 리미티드 신규한 호흡 제어 조절 화합물, 및 그의 제조 및 사용 방법
ES2925951T3 (es) 2015-07-22 2022-10-20 John Hsu Composición que comprende un agente terapéutico y un estimulante respiratorio y métodos para su uso
MX2018001435A (es) 2015-08-24 2018-04-20 Zogenix International Ltd Metodos de tratamiento del sindrome de lennox-gastaut con fenfluramina.
US20220193082A1 (en) 2015-09-14 2022-06-23 Zogenix International Limited Combination treatment of specific forms of epilepsy
US20170071949A1 (en) 2015-09-14 2017-03-16 Zogenix International Limited Combination treatment of specific forms of epilepsy
EP3170807B1 (en) 2015-11-23 2019-12-11 Frau Pharma S.r.l. New method for synthesis of fenfluramine
JP6893213B2 (ja) 2015-12-22 2021-06-23 ゾゲニクス インターナショナル リミテッド フェンフルラミン組成物およびその調製法
WO2017112701A1 (en) 2015-12-22 2017-06-29 Zogenix International Limited Metabolism resistant fenfluramine analogs and methods of using the same
JP6753418B2 (ja) 2016-01-14 2020-09-09 Ａｇｃ株式会社 フッ素樹脂含有溶液、フッ素樹脂含有溶液の製造方法、塗料組成物および塗装物品
RU2746000C2 (ru) 2016-08-24 2021-04-05 Зодженикс Интернэшнл Лимитед Состав для ингибирования образования агонистов 5-ht2b и способы его применения
US20190083425A1 (en) 2016-08-24 2019-03-21 Zogenix International Limited Formulation for inhibiting formation of 5-ht2b agonists and methods of using same
US20180092864A1 (en) 2016-09-30 2018-04-05 Zogenix International Limited Compositions and methods for treating seizure disorders
CA3062247A1 (en) 2017-05-09 2018-11-15 Zogenix International Limited Methods of treating doose syndrome using fenfluramine
US20190091173A1 (en) 2017-09-26 2019-03-28 Zogenix International Limited Method of increasing time between convulsive seizures
US20190247333A1 (en) 2017-09-26 2019-08-15 Zogenix International Limited Method of reduction in convulsive seizure frequency
US20190091179A1 (en) 2017-09-26 2019-03-28 Zogenix International Limited Congnitive function with fenfluramine
US10682317B2 (en) 2017-09-26 2020-06-16 Zogenix International Limited Ketogenic diet compatible fenfluramine formulation
WO2019067413A1 (en) 2017-09-26 2019-04-04 Zogenix International Limited USE OF A FENFLURAMINE FORMULATION TO REDUCE THE NUMBER AND FREQUENCIES OF CONVULSIVE CRISES IN PATIENT POPULATIONS
US11352882B2 (en) 2018-03-12 2022-06-07 Cameron International Corporation Plug assembly for a mineral extraction system
BR112020021324A2 (pt) 2018-04-18 2021-01-19 The Trustees Of Columbia University In The City Of New York Terapia gênica para doenças causadas por pools de nucleotídeos em desequilíbrio incluindo síndromes de depleção do dna mitocondrial
US11571397B2 (en) 2018-05-11 2023-02-07 Zogenix International Limited Compositions and methods for treating seizure-induced sudden death
WO2019241005A1 (en) 2018-06-14 2019-12-19 Zogenix International Limited Compositions and methods for treating respiratory depression with fenfluramine
EP3820459A1 (en) 2018-07-10 2021-05-19 Zogenix International Limited Fenfluramine for use for treating epilepsy or epileptic encephalopathy in patients without pulmonary hypertension
MA53329A (fr) 2018-07-27 2022-03-02 Xenon Pharmaceuticals Inc Méthodes de traitement de l'épilepsie
WO2020105005A1 (en) 2018-11-19 2020-05-28 Zogenix International Limited Methods of treating rett syndrome using fenfluramine
US20210401776A1 (en) 2018-11-30 2021-12-30 Zogenix International Limited Method of treating refractory epilepsy syndromes using fenfluramine enantiomers
US20220133652A1 (en) 2019-02-25 2022-05-05 Zogenix International Limited A formulation for improving seizure control
US20210299064A1 (en) 2020-02-05 2021-09-30 Zogenix International Limited Method of treating patients with lennox-gastaut syndrome
US11612574B2 (en) 2020-07-17 2023-03-28 Zogenix International Limited Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
US20220096514A1 (en) 2020-09-29 2022-03-31 Zogenix International Limited Methods of treating thymidine kinase 2 deficiency by administering deoxycytidine and deoxythymidine

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