DK1729753T3 - Anvendelse af en NMDA-receptor-antagonist til behandling af tinnitus induceret ved kokleær excitotoksicitet - Google Patents

Anvendelse af en NMDA-receptor-antagonist til behandling af tinnitus induceret ved kokleær excitotoksicitet

Info

Publication number
DK1729753T3
DK1729753T3 DK05736619T DK05736619T DK1729753T3 DK 1729753 T3 DK1729753 T3 DK 1729753T3 DK 05736619 T DK05736619 T DK 05736619T DK 05736619 T DK05736619 T DK 05736619T DK 1729753 T3 DK1729753 T3 DK 1729753T3
Authority
DK
Denmark
Prior art keywords
receptor antagonist
nmda receptor
treat tinnitus
cochlear excitotoxicity
tinnitus induced
Prior art date
Application number
DK05736619T
Other languages
English (en)
Inventor
Matthieu Guitton
Jean-Luc Puel
Remy Pujol
Original Assignee
Auris Medical Ag
Inst Nat Sante Rech Med
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=34966520&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DK1729753(T3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Auris Medical Ag, Inst Nat Sante Rech Med filed Critical Auris Medical Ag
Application granted granted Critical
Publication of DK1729753T3 publication Critical patent/DK1729753T3/da

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/01Hydrocarbons
    • A61K31/015Hydrocarbons carbocyclic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/02Halogenated hydrocarbons
    • A61K31/025Halogenated hydrocarbons carbocyclic
    • A61K31/03Halogenated hydrocarbons carbocyclic aromatic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/439Heterocyclic 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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/662Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/16Otologicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
DK05736619T 2004-03-29 2005-03-29 Anvendelse af en NMDA-receptor-antagonist til behandling af tinnitus induceret ved kokleær excitotoksicitet DK1729753T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US10/812,298 US8268866B2 (en) 2004-03-29 2004-03-29 Methods for the treatment of tinnitus induced by cochlear excitotoxicity
PCT/EP2005/003254 WO2005094799A2 (en) 2004-03-29 2005-03-29 Use of an nmda receptor antagonist for the treatment of tinnitus induced by cochlear excitotoxicity

Publications (1)

Publication Number Publication Date
DK1729753T3 true DK1729753T3 (da) 2009-11-23

Family

ID=34966520

Family Applications (1)

Application Number Title Priority Date Filing Date
DK05736619T DK1729753T3 (da) 2004-03-29 2005-03-29 Anvendelse af en NMDA-receptor-antagonist til behandling af tinnitus induceret ved kokleær excitotoksicitet

Country Status (21)

Country Link
US (1) US8268866B2 (da)
EP (2) EP2077108A1 (da)
JP (2) JP4927706B2 (da)
KR (2) KR101429735B1 (da)
CN (2) CN104906079B (da)
AU (1) AU2005229543B2 (da)
BR (1) BRPI0508251A (da)
CA (1) CA2558896C (da)
CY (1) CY1110495T1 (da)
DE (1) DE602005015562D1 (da)
DK (1) DK1729753T3 (da)
ES (1) ES2330350T3 (da)
IL (1) IL177490A (da)
MX (1) MXPA06011078A (da)
NZ (1) NZ549399A (da)
PL (1) PL1729753T3 (da)
PT (1) PT1729753E (da)
RU (1) RU2380094C2 (da)
SI (1) SI1729753T1 (da)
WO (1) WO2005094799A2 (da)
ZA (1) ZA200607161B (da)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9072662B2 (en) 2004-03-29 2015-07-07 Auris Medical Ag Methods for the treatment of tinnitus induced by cochlear excitotoxicity
US8268866B2 (en) 2004-03-29 2012-09-18 Matthieu Guitton Methods for the treatment of tinnitus induced by cochlear excitotoxicity
US20060063802A1 (en) * 2004-03-29 2006-03-23 Matthieu Guitton Methods for the treatment of tinnitus induced by cochlear excitotoxicity
CN101163481A (zh) * 2005-03-04 2008-04-16 纽罗赛斯特克公司 改进的加环利定制剂
CN101309667A (zh) * 2005-09-28 2008-11-19 奥里斯医学股份有限公司 治疗内耳疾病的药用合成物
US7803148B2 (en) 2006-06-09 2010-09-28 Neurosystec Corporation Flow-induced delivery from a drug mass
US8175712B2 (en) * 2006-09-05 2012-05-08 The Penn State Research Foundation Homotopic conditioning of the brain stem baroreflex of a subject
US11969501B2 (en) 2008-04-21 2024-04-30 Dompé Farmaceutici S.P.A. Auris formulations for treating otic diseases and conditions
MX2010011545A (es) 2008-04-21 2011-04-11 Otonomy Inc Formulaciones para tratar enfermedades y afecciones del oido.
EP2303227B1 (en) 2008-05-14 2021-10-06 Otonomy, Inc. Controlled release corticosteroid compositions and methods for the treatment of otic disorders
US8648119B2 (en) * 2008-05-23 2014-02-11 Otonomy, Inc. Controlled release immunomodulator compositions and methods for the treatment of otic disorders
US8846770B2 (en) * 2008-06-18 2014-09-30 Otonomy, Inc. Controlled release aural pressure modulator compositions and methods for the treatment of OTIC disorders
WO2010011466A2 (en) 2008-06-27 2010-01-28 Otonomy, Inc. Controlled-release cns modulating compositions and methods for the treatment of otic disorders
US8349353B2 (en) * 2008-06-27 2013-01-08 Otonomy, Inc. Controlled release cytotoxic agent compositions and methods for the treatment of otic disorders
WO2010008995A2 (en) * 2008-07-14 2010-01-21 Otonomy, Inc. Controlled-release apoptosis modulating compositions and methods for the treatment of otic disorders
CA2731769C (en) * 2008-07-21 2013-09-10 Otonomy, Inc. Controlled-release otic structure modulating and innate immune system modulating compositions and methods for the treatment of otic disorders
US8496957B2 (en) * 2008-07-21 2013-07-30 Otonomy, Inc Controlled release auris sensory cell modulator compositions and methods for the treatment of otic disorders
US20100016450A1 (en) * 2008-07-21 2010-01-21 Otonomy, Inc. Controlled release delivery devices for the treatment of otic disorders
US8784870B2 (en) * 2008-07-21 2014-07-22 Otonomy, Inc. Controlled release compositions for modulating free-radical induced damage and methods of use thereof
US8318817B2 (en) 2008-07-21 2012-11-27 Otonomy, Inc. Controlled release antimicrobial compositions and methods for the treatment of otic disorders
US8399018B2 (en) * 2008-07-21 2013-03-19 Otonomy, Inc. Controlled release ion channel modulator compositions and methods for the treatment of otic disorders
JP2012506436A (ja) 2008-10-22 2012-03-15 ハウス イアー インスティトゥート 代謝型グルタミン酸受容体の調節による内耳の疾病の処置および/または予防
CA2732686C (en) * 2008-12-22 2017-10-03 Otonomy, Inc. Controlled release auris sensory cell modulator compositions and methods for the treatment of otic disorders
WO2012098000A1 (en) * 2011-01-20 2012-07-26 Merz Pharma Gmbh & Co. Kgaa Neramexane for the treatment or prevention of tinnitus related with stress or acute hearing loss
JP5941159B2 (ja) 2011-12-12 2016-06-29 オトラーヌム アーゲー 聴覚系における塩素イオン共輸送体nkcc1の調節による耳鳴の治療
US8920855B1 (en) 2012-10-30 2014-12-30 Setem Hemth, Inc Methods of topically treating tinnitus and related disorders
US9486405B2 (en) 2013-08-27 2016-11-08 Otonomy, Inc. Methods for the treatment of pediatric otic disorders
JP2017513870A (ja) * 2014-04-23 2017-06-01 オーリス メディカル エージーAuris Medical Ag 耳鳴りの治療と予防のための方法及び組成物
US11207316B2 (en) 2014-05-30 2021-12-28 West Virginia University Ketamine or dextromethorphan formulations and methods of use
CN109689027A (zh) 2016-06-29 2019-04-26 奥德纳米有限公司 甘油三酯耳用制剂及其用途
WO2018053173A1 (en) 2016-09-16 2018-03-22 Otonomy, Inc. Otic gel formulations for treating otitis externa
US10561736B1 (en) 2019-01-09 2020-02-18 Spiral Therapeutics, Inc. Apoptosis inhibitor formulations for prevention of hearing loss

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3254124A (en) * 1962-06-29 1966-05-31 Parke Davis & Co Aminoketones and methods for their production
CH535201A (de) 1969-12-19 1973-03-31 Bristol Myers Co Verfahren zur Spaltung von racemischen 2-(o-Chlorphenyl)-2-methylaminocyclohexanon in die optisch-aktiven Isomeren
AU5171293A (en) * 1992-10-14 1994-05-09 Regents Of The University Of Colorado, The Ion-pairing of drugs for improved efficacy and delivery
US5421818A (en) * 1993-10-18 1995-06-06 Inner Ear Medical Delivery Systems, Inc. Multi-functional inner ear treatment and diagnostic system
DE69434794T2 (de) * 1994-09-22 2007-07-12 Smith, Richard Alan, La Jolla Kombination von dextromethorphan mit quinidine oder quinine sulfat zur behandlung verschiedener refraktärer störungen
US5945409A (en) * 1995-03-10 1999-08-31 Wilson T. Crandall Topical moisturizing composition and method
US5654337A (en) * 1995-03-24 1997-08-05 II William Scott Snyder Topical formulation for local delivery of a pharmaceutically active agent
DE19528388A1 (de) * 1995-08-02 1997-02-06 Hans Peter Prof Dr Med Zenner Verwendung von Adamantan-Derivaten zur Behandlung von Erkrankungen des Innenohrs
TW450807B (en) 1995-09-15 2001-08-21 Pfizer Pharmaceutical compositions for treating tinnitus comprising neuroprotective agents
US5746961A (en) * 1995-12-04 1998-05-05 Michael J. Stevenson Method for enhancement of the surfaces of molded plastic products
AU2676397A (en) 1996-04-18 1997-11-07 University Technology Corporation Methods for treating middle and inner ear disorders
AU4424697A (en) 1996-09-11 1998-04-02 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The The use of functional n-methyl-d-aspartate antagonists to ameliorate or prevent aminoglycoside-induced ototoxicity
US6045528A (en) * 1997-06-13 2000-04-04 Intraear, Inc. Inner ear fluid transfer and diagnostic system
US6309410B1 (en) * 1998-08-26 2001-10-30 Advanced Bionics Corporation Cochlear electrode with drug delivery channel and method of making same
DE19853299C2 (de) * 1998-11-19 2003-04-03 Thomas Lenarz Katheter zur Applikation von Medikamenten in Flüssigkeitsräumen des menschlichen Innenohrs
US6120484A (en) * 1999-02-17 2000-09-19 Silverstein; Herbert Otological implant for delivery of medicament and method of using same
US6017961A (en) * 1999-07-08 2000-01-25 Flores; John Anthony Ketamine and n-butyl-p-aminobezoate in PLO
DE19936719A1 (de) * 1999-08-06 2001-02-15 Gruenenthal Gmbh Substituierte 1,5-Dihydropyrrol-2-on-Derivate
US6265379B1 (en) * 1999-10-13 2001-07-24 Allergan Sales, Inc. Method for treating otic disorders
JP2001187737A (ja) 1999-10-18 2001-07-10 Toyama Chem Co Ltd 聴力改善剤
DE10025238A1 (de) 2000-05-22 2001-11-29 Gruenenthal Gmbh Verwendung substituierter 1-Amino-5-phenylpentan-3-ol- und/oder 1-Amino-6-phenylhexan-3-ol- Verbindungen als Arzneimittel
BRPI0002693B8 (pt) 2000-06-19 2021-05-25 Cristalia Produtos Quim Farmaceuticos Ltda processo de obtenção dos enantiômeros da cetamina e seus sais farmaceuticamente aceitáveis
DE10048969A1 (de) 2000-08-23 2002-03-14 Mueller Schwefe Gerhard Verwendung von Flupirtin zur Tinnitusbehandlung
DE10044649A1 (de) 2000-09-08 2002-07-04 Gruenenthal Gmbh Substituierte 4-Phenyl-1-(1-phenyl-cyclohexyl)-1,2,3,6-tetrahydropyridine
US6924273B2 (en) * 2000-10-03 2005-08-02 Scott W. Pierce Chondroprotective/restorative compositions and methods of use thereof
DE10124953A1 (de) 2001-05-21 2002-12-12 Marlies Knipper Substanz für die therapeutische Behandlung von Tinnitus
US6638981B2 (en) * 2001-08-17 2003-10-28 Epicept Corporation Topical compositions and methods for treating pain
US20030143195A1 (en) * 2002-01-30 2003-07-31 Pinsker Judy Senior Use of histamine as a drug delivery enhancing compound for use in transmucosal or transdermal delivery
US6638081B2 (en) * 2002-03-22 2003-10-28 Hon Hai Precision Ind. Co., Ltd. Electrical connector
JP2006502158A (ja) 2002-09-06 2006-01-19 デュレクト コーポレーション グルタメート媒介神経伝達のモジュレーターの内耳への送達
US6969383B2 (en) * 2002-09-27 2005-11-29 Medtronic, Inc. Method for treating severe tinnitus
US6656172B1 (en) * 2002-09-27 2003-12-02 Medtronic, Inc. Method for treating severe tinnitus
DE50312412D1 (en) 2002-11-12 2010-03-25 Gruenenthal Gmbh 4-hydroxymethyl-1-aryl-cyclohexylamin-derivative
US7220431B2 (en) * 2002-11-27 2007-05-22 Regents Of The University Of Minnesota Methods and compositions for applying pharmacologic agents to the ear
EP1438942A1 (en) 2003-01-17 2004-07-21 Schering Oy An otorhinological drug delivery device
US7709207B2 (en) 2003-05-16 2010-05-04 Universite Laval Method for identifying compounds for treatment of pain
CA2548892C (en) 2003-12-12 2015-10-27 Eran Eilat Compositions for treatment of ear disorders and methods of use thereof
GB0402118D0 (en) 2004-01-30 2004-03-03 Merck Sharp & Dohme Polymorphic forms of a GABAA agonist
US8268866B2 (en) * 2004-03-29 2012-09-18 Matthieu Guitton Methods for the treatment of tinnitus induced by cochlear excitotoxicity

Also Published As

Publication number Publication date
PL1729753T3 (pl) 2010-01-29
CN104906079B (zh) 2018-01-19
WO2005094799A2 (en) 2005-10-13
SI1729753T1 (sl) 2009-12-31
CN1972677B (zh) 2015-03-11
CN104906079A (zh) 2015-09-16
BRPI0508251A (pt) 2007-07-31
CN1972677A (zh) 2007-05-30
WO2005094799A3 (en) 2006-03-02
AU2005229543B2 (en) 2009-12-03
RU2380094C2 (ru) 2010-01-27
EP1729753A2 (en) 2006-12-13
NZ549399A (en) 2009-12-24
MXPA06011078A (es) 2007-11-20
IL177490A0 (en) 2006-12-10
CA2558896C (en) 2012-11-20
EP1729753B1 (en) 2009-07-22
KR101451414B1 (ko) 2014-10-22
CA2558896A1 (en) 2005-10-13
US20050214338A1 (en) 2005-09-29
KR101429735B1 (ko) 2014-08-12
RU2006138153A (ru) 2008-05-10
IL177490A (en) 2013-10-31
ZA200607161B (en) 2007-11-28
ES2330350T3 (es) 2009-12-09
JP2011105740A (ja) 2011-06-02
JP4927706B2 (ja) 2012-05-09
DE602005015562D1 (de) 2009-09-03
US8268866B2 (en) 2012-09-18
AU2005229543A1 (en) 2005-10-13
JP2007530622A (ja) 2007-11-01
KR20120049364A (ko) 2012-05-16
EP2077108A1 (en) 2009-07-08
KR20130103615A (ko) 2013-09-23
CY1110495T1 (el) 2015-04-29
PT1729753E (pt) 2009-09-21

Similar Documents

Publication Publication Date Title
DK1729753T3 (da) Anvendelse af en NMDA-receptor-antagonist til behandling af tinnitus induceret ved kokleær excitotoksicitet
DK1828164T3 (da) Fremgangsmåde til fremstilling af N-phenylpyrazol-1-carboxamider
DK1778668T3 (da) Fremgangsmåde til fremstilling af dihydropteridion
DK1720866T3 (da) Fremgangsmåde
ES2411907T8 (es) Uso terapéutico de anticuerpos antirreceptor TWEAK
DK2086944T3 (da) Fremgangsmåde til fremstilling af difluormethylpyrazolylcarboxylater
DK1706112T3 (da) Fremgangsmåder til at behandle en inflammatorisk-beslægtet sygdom
DK2068874T3 (da) Fremgangsmåder til behandling af multiple myelom med anvendelse af kombinationsterapier baseret på anti-cs1 antistoffer
DK2019825T3 (da) Inhibitorer af human immundefektvirus-replikation
DK1893586T3 (da) Fremgangsmåde til fremstilling af 1-alkyl-3-phenyluraciler
DK2094676T3 (da) Ny fremgangsmåde til fremstillingen af 2-iminothiazolidin-4-on-derivater
BRPI0816092A2 (pt) Máscara laríngea
DK1813678T3 (da) Fremgangsmåde til fremstilling af glycogen
DE602007006040D1 (de) Hemmstoffe des progesteron-rezeptors
DK1943242T3 (da) Piperidin-4-yl-pyridazin-3-ylamin-derivater som hurtigt opløsende antagonister af dopamin-2-receptorer
ATE481405T1 (de) Thiazolpyrazolopyrimidine als antagonisten des crf1-rezeptors
DK1763520T3 (da) Anvendelse af trisubstituerede benzopyranoner
CR8618A (es) Nuevos derivados de bencil (dieno)-lactamas
DK1841433T3 (da) Præparat til behandling af lidelser i centralnervesystemet
DK1831223T3 (da) Fremgangsmåde til fremstilling af L-biopterin
DK1814555T3 (da) S-mirtazapin til behandling af hedeture
NO20043305D0 (no) Preparation of lodixanol
DK1856035T3 (da) Fremgangsmåde til fremstilling af beskyttelse amidiner
DK2091938T3 (da) Piperidinylaminopyridaziner og anvendelse deraf som hurtigt opløsende antagonister af dopamin-2-receptorer
DK1912961T3 (da) Fremgangsmåde til fremstilling af bepromolin