EP1740175A1 - Utilisation d'un antagoniste de cgrp en combinaison avec un inhibiteur de recaptage de la serotonine pour le traitement des migraines - Google Patents

Utilisation d'un antagoniste de cgrp en combinaison avec un inhibiteur de recaptage de la serotonine pour le traitement des migraines

Info

Publication number
EP1740175A1
EP1740175A1 EP05735425A EP05735425A EP1740175A1 EP 1740175 A1 EP1740175 A1 EP 1740175A1 EP 05735425 A EP05735425 A EP 05735425A EP 05735425 A EP05735425 A EP 05735425A EP 1740175 A1 EP1740175 A1 EP 1740175A1
Authority
EP
European Patent Office
Prior art keywords
piperidinyl
dihydro
carbonyl
dibromo
amino
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP05735425A
Other languages
German (de)
English (en)
Inventor
Henri Doods
Klaus Rudolf
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
Original Assignee
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
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
Priority claimed from DE102004019736A external-priority patent/DE102004019736A1/de
Priority claimed from DE102004063754A external-priority patent/DE102004063754A1/de
Application filed by Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH and Co KG filed Critical Boehringer Ingelheim International GmbH
Publication of EP1740175A1 publication Critical patent/EP1740175A1/fr
Withdrawn legal-status Critical Current

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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • 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
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • Migraine is one of the most common neurological disorders and includes periodic bouts of headache and nausea, as well as a variety of other symptoms. Although significant progress has been made, the pathophysiology of migraines is still not understood. However, several observations indicate involvement of the calcitonin gene-related peptide (CGRP). Migraine headaches include activation of the trigeminal system and enlargement of the cranial vessels. CGRP is localized to neurons in trigeminal ganglia, and CGRP levels are elevated during a migraine attack, which is thought to cause the observed vasodilation. Accordingly, it is conceivable that the inhibition of the enlargement of the cranial vessels caused by CGRP may allow a new treatment for migraine headaches.
  • CGRP calcitonin gene-related peptide
  • migraines Medicines for migraines that are widely used are so-called “triptans”, for example sumatriptan and zolmitriptan. These compounds elicit their effects against migraines because of their vasoconstrictive properties and presumably their inhibition of the release of the neuropeptide calcitonin gene-related peptide (CGRP) (Ferrari, MD, Saxena, PR (1995), 5-HT1 receptors in migraine pathophysiology and treatment , Eur. J. Neurology, 2, 5-21; Johnson, KW, Phebus, LA, Cohen, ML (1998), Serotonin in migraine: Theiroes, animal modeis and emerging therapies, Progress in Drug Research, Vol.
  • CGRP neuropeptide calcitonin gene-related peptide
  • WO 98/11128 discloses modified amino acids with CGRP-antagonistic properties, their use and methods for their production as well as their use for the production and purification of antibodies and as labeled compounds in RIA and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.
  • the modified amino acids are therefore suitable for the acute and prophylactic treatment of headaches, in particular migraines and cluster headache.
  • the present invention provides a method of treating or preventing indications selected from the group consisting of headache, migraine and cluster headache, the method comprising co-administering a therapeutically effective amount of a CGRP antagonist ( A) or a physiologically acceptable salt thereof and a therapeutically effective amount of a serotonin reuptake inhibitor (B) or a physiologically acceptable salt thereof to a person in need of such treatment.
  • a CGRP antagonist A
  • B serotonin reuptake inhibitor
  • active ingredient (A) all pharmaceutically acceptable active ingredients which antagonize the known effects of CGRP or which inhibit the release of CGRP from sensory nerve endings can be used as the active ingredient (A).
  • Possible CGRP antagonists (A) are, for example, the amino acid derivatives described in WO 98/11128 or DE 199 11 039, and also the non-peptide active ingredients described in WO 98/56779, WO 98/09630 and WO 97/09046.
  • the CGRP antagonist (A) is preferably selected from the group consisting of
  • Citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, trazodone or the physiologically tolerable salts thereof can be used as serotonin reuptake inhibitors (B).
  • Duloxetine is preferably used.
  • the dose for the serotonin reuptake inhibitor (B) is about 1/50 of the lowest normally recommended dose up to 1/1 of the normally recommended dose, by oral, nasal, inhalation, subcutaneous or intravenous routes.
  • the CGRP antagonist (A) or a physiologically tolerable salt thereof can be administered intravenously or subcutaneously in a dosage of 0.0001 to 3 mg / kg body weight, orally in a dosage of 0.1 to 20 mg / kg body weight or on nasalem or inhalation route in a dosage of 0.1 to 10 mg / kg body weight once, twice or three times a day in combination with
  • a serotonin reuptake inhibitor (B) or a physiologically acceptable salt thereof administered orally at a dose of 0.03 to 1.43 mg / kg body weight once, twice or three times a day or
  • the present invention provides a pharmaceutical composition for the treatment or prevention of headache, migraine or cluster headache, which contains a therapeutically effective amount of a CGRP antagonist (A) or a physiologically tolerable salt thereof and a serotonin reuptake inhibitor (B ) or a physiologically tolerable salt thereof, as a combined preparation for simultaneous or sequential administration.
  • a CGRP antagonist A
  • a physiologically tolerable salt thereof a physiologically tolerable salt thereof
  • B serotonin reuptake inhibitor
  • a pharmaceutical composition according to the invention can have a single dosage unit of 0.1 to 1500 mg, preferably 0.3 to 1000 mg, particularly preferably 5 to 750 mg, of the CGRP antagonist (A) or an equivalent amount of a physiologically tolerable salt thereof and
  • All doses or dosage units of a physiologically compatible salt of one of the above-mentioned active compounds are to be understood as the dose or dosage of the active compound itself.
  • a pharmaceutical composition according to the invention can be a kit of parts for the treatment or prevention of headache, migraine or cluster headache, the kit comprising:
  • a first enclosure containing a pharmaceutical composition comprising a therapeutically effective amount of the CGRP antagonist (A) or a physiologically acceptable salt thereof and one or more physiologically acceptable diluents and / or carriers;
  • a second enclosure containing a pharmaceutical composition comprising a serotonin reuptake inhibitor (B) or a physiologically acceptable salt thereof and one or more physiologically acceptable diluents and / or carriers.
  • a third aspect of the present invention is the use of the CGRP antagonist (A) or a physiologically acceptable salt thereof in combination with a serotonin reuptake inhibitor (B) or a physiologically acceptable salt thereof for the manufacture of a pharmaceutical composition for treatment or prevention of headache, migraine or cluster headache.
  • the CGRP antagonist (A) or a physiologically tolerable salt thereof can be administered, for example, using one of the pharmaceutical formulations described in the examples.
  • the examples that follow describe pharmaceutical compositions containing the CGRP antagonist (A) or a physiologically acceptable salt thereof and a serotonin reuptake inhibitor (B) or a physiologically acceptable salt thereof.
  • Example 1a
  • composition / tablet Composition / tablet:
  • CGRP antagonist (A), serotonin reuptake inhibitor (B) and lactose (fine) are mixed homogeneously in a suitable mixer (e.g. Diosna P2); then the mixture is granulated with an aqueous povidone solution.
  • the granules are sieved with a Kressner sieve with 1.6 mm and dried at 40 ° C for 2 hours.
  • the granulate is then passed through a suitable mill, e.g. a Comill sieved at 3000 rpm with a mesh size of 1.1 mm.
  • the granules are then mixed with grospovidone for 5 minutes and then with magnesium stearate for 1 minute.
  • the mixture thus obtained is pressed in a tablet press into tablets with a suitable diameter.
  • CGRP antagonist (A), serotonin reuptake inhibitor (B), lactose (fine) and microcrystalline cellulose are mixed homogeneously in a suitable mixer (e.g. Diosna P2); the mixture is then granulated with water.
  • the granules are sieved with a Kressner sieve with 1.6 mm and dried at 40 ° C for 2 hours.
  • the granules are then passed in a suitable mill, e.g. a Comill sieved at 3000 rpm with a mesh size of 1.1 mm.
  • the granules are then mixed with croscarmellose for 5 minutes and then with magnesium stearate for 1 minute.
  • the mixture thus obtained is pressed in a tablet press into tablets with a suitable diameter.
  • the active ingredient is dissolved / suspended in water with stirring and optionally heating.
  • the isotonans mannitol is added and the solution is made up to the final volume with water.
  • Aqueous solution for intranasal use containing 40% CGRP antagonist (A) or an equivalent amount of a physiologically acceptable salt thereof and 10% serotonin reuptake inhibitor (B) or an equivalent amount of a physiologically acceptable salt thereof and 1.5% Labrasol
  • the active ingredients are dissolved / suspended in water with stirring and optionally heating.
  • the isotonans mannitol and Labrasol are added and the solution is made up to the final volume with water.
  • the pharmaceutical substances according to the invention can also be in the form of small particles such as e.g.
  • Pellets are made.
  • the active ingredient can be based on neutral pellets
  • Sucrose and starch or microcrystalline cellulose exist.
  • the production takes place in the following steps:
  • Serotonin Reuptake Inhibitor (B) 40 parts by weight
  • Hydroxypropyl cellulose is dissolved in 250 parts by weight of 2-propanol with stirring and then the active ingredients and talc are dispersed in this solution with stirring.
  • the active ingredient-containing pellets are sieved using a sieve with a nominal mesh size of 1.25 mm.
  • the good fraction (grain size ⁇ 1.25 mm) is processed further.
  • the active substance layer is generally built up in the same way, but the type of active substance and the amount, type of binder and quantity, amount of talc and water, isopropanol or amount of ethanol are varied.
  • the medicinal substances according to the invention can also be produced in the form of extrudates which, after cutting / spheronization, are filled directly into capsules or processed into tablets after grinding.
  • the production takes place in the following steps:
  • Serotonin Reuptake Inhibitor (B) 80 parts by weight
  • the extrusion strands are rounded off to form pellets in a spheronizer, rounding for approx. 3 minutes at approx. 850 RPM.
  • the pellets are dried in a fluidized bed dryer at 80 ° C. for about 1.5 hours.
  • the core material is fractionated using a tumbler screening machine with different screening trays with nominal mesh sizes from 0.71 to 1.25 mm. The appropriate good fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used.
  • Serotonin Reuptake Inhibitor (B) 60 parts by weight 200 parts by weight of the CGRP antagonist (A), 60 parts by weight of the Serotonin reuptake inhibitor (B), 40 parts by weight of the poloxamer and 6 parts by weight of the Povidon K25 are mixed in a wheel mixer for 15 minutes. The powder mixture is then introduced into a twin-screw extruder at a rate of approx. 1 kg / h. The temperature is controlled so that a target torque of approx. 19% is generated in the extruder. The extrusion is carried out via a die plate with 0.8 mm diameter holes.
  • the emerging extrusion strands are cut with a head tee, the extrusion strands are rounded off to pellets in a spheronizer, rounding for approx. 3 minutes at approx. 850 RPM at approx. 40 ° C. Drying of the pellets at 80 ° C approximately "1.5 h in a fluidized bed dryer.
  • the core material is fractionated using a tumbler screening machine with different screening trays with nominal mesh sizes from 0.71 to 1.25 mm.
  • the appropriate good fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • compositions can vary and are shown below in tabular form.
  • Granules are further processed into tablets using conventional tableting aids as in Example 1.
  • X50 particle size / drop size, below which 50% of the particle quantity is in the range of 1.5 to 8 ⁇ m with respect to the volume distribution of the individual particles / drops
  • Q (5.8) corresponds to the quantity of particles which is below 5.8 ⁇ m in relation to the volume distribution of the droplets
  • the spray thus obtained is dried with the aid of a drying gas with an inlet temperature between 130 ° C and 200 ° C and an outlet temperature of 40 ° C to 120 ° C Spray gas 1 Nm 3 / h to 15 Nm 3 / h and the volume flow of the drying gas 15 Nm 3 / h to 150 Nm 3 / h.
  • the dried solid content is collected by means of a gravity separator and / or filter unit.
  • 1 capsule for powder inhalation contains:
  • the active substance is produced as a spherically nanostructured active substance particle and mixed homogeneously with lactose. The mixture is packed in hard gelatin capsules.
  • the active ingredient is dissolved in physiological saline.
  • the hard wax is melted and the active ingredients are suspended in the mass.
  • the mass is then poured into suitable suppository molds.
  • the dose amounts can vary and are shown in the table below.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Abstract

La présente invention concerne un procédé de traitement ou de prévention de céphalées, de migraines ou de céphalées vasculaires de Horton. Ledit procédé consiste à administrer conjointement une quantité thérapeutique efficace d'un antagoniste de CGRP (A) ou d'un sel physiologiquement acceptable de celui-ci, et une quantité thérapeutique efficace d'un inhibiteur de recapatage de la sérotonine (B) ou d'un sel physiologiquement acceptable de celui-ci. L'invention concerne également les compositions pharmaceutiques correspondantes et leur fabrication.
EP05735425A 2004-04-20 2005-04-18 Utilisation d'un antagoniste de cgrp en combinaison avec un inhibiteur de recaptage de la serotonine pour le traitement des migraines Withdrawn EP1740175A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE102004019736A DE102004019736A1 (de) 2004-04-20 2004-04-20 Verwendung des CGRP-Antagonisten 1[N2[3,5 Dibrom-N-[[4(3,4 dihydro-2(1H)-oxochinazolin-3-yl)-1-piperidinyl]-carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazin in Kombination mit (+)-N-Methyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamin zur Behandlung von Migräne
DE102004063754A DE102004063754A1 (de) 2004-12-29 2004-12-29 Verwendung eines CGRP-Antagonisten in Kombination mit einem Serotonin-Wiederaufnahme-Hemmer zur Behandlung von Migräne
PCT/EP2005/004076 WO2005102322A1 (fr) 2004-04-20 2005-04-18 Utilisation d'un antagoniste de cgrp en combinaison avec un inhibiteur de recaptage de la serotonine pour le traitement des migraines

Publications (1)

Publication Number Publication Date
EP1740175A1 true EP1740175A1 (fr) 2007-01-10

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ID=34965481

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Application Number Title Priority Date Filing Date
EP05735425A Withdrawn EP1740175A1 (fr) 2004-04-20 2005-04-18 Utilisation d'un antagoniste de cgrp en combinaison avec un inhibiteur de recaptage de la serotonine pour le traitement des migraines

Country Status (4)

Country Link
EP (1) EP1740175A1 (fr)
JP (1) JP2007533685A (fr)
CA (1) CA2563687A1 (fr)
WO (1) WO2005102322A1 (fr)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7842808B2 (en) 2002-06-05 2010-11-30 Bristol-Myers Squibb Company Anti-migraine spirocycles
US7220862B2 (en) 2002-06-05 2007-05-22 Bristol-Myers Squibb Company Calcitonin gene related peptide receptor antagonists
TW200524601A (en) 2003-12-05 2005-08-01 Bristol Myers Squibb Co Heterocyclic anti-migraine agents
TW200533398A (en) 2004-03-29 2005-10-16 Bristol Myers Squibb Co Novel therapeutic agents for the treatment of migraine
US7384931B2 (en) 2004-11-03 2008-06-10 Bristol-Myers Squibb Company Constrained compounds as CGRP-receptor antagonists
US7384930B2 (en) 2004-11-03 2008-06-10 Bristol-Myers Squibb Company Constrained compounds as CGRP-receptor antagonists
US7449586B2 (en) 2004-12-03 2008-11-11 Bristol-Myers Squibb Company Processes for the preparation of CGRP-receptor antagonists and intermediates thereof
US7834007B2 (en) 2005-08-25 2010-11-16 Bristol-Myers Squibb Company CGRP antagonists
BRPI0618705B8 (pt) 2005-11-14 2021-05-25 Labrys Biologics Inc anticorpos antagonistas humanizados direcionados contra peptídeo relacionado ao gene da calcitonina, composição farmacêutica e uso dos mesmos
EP2265287B1 (fr) 2008-03-04 2018-09-05 Teva Pharmaceuticals International GmbH Procédés de traitement d'une douleur chronique
EP2470207A1 (fr) 2009-08-28 2012-07-04 Rinat Neuroscience Corporation Procédés de traitement de la douleur viscérale par administration d'anticorps antagonistes dirigés contre le peptide associé au gène de la calcitonine
JP6568099B2 (ja) 2014-03-21 2019-08-28 テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハーＴｅｖａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｔｅｒｎａｔｉｏｎａｌ ＧｍｂＨ カルシトニン遺伝子関連ペプチドに対するアンタゴニスト抗体及びその使用方法
US10556945B2 (en) 2014-03-21 2020-02-11 Teva Pharmaceuticals International Gmbh Antagonist antibodies directed against calcitonin gene-related peptide and methods using same
KR20220031944A (ko) 2016-09-23 2022-03-14 테바 파마슈티컬스 인터내셔널 게엠베하 불응성 편두통의 치료

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19911039A1 (de) * 1999-03-12 2000-09-14 Boehringer Ingelheim Pharma Abgewandelte Aminosäureamide, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
DE10139410A1 (de) * 2001-08-17 2003-02-27 Boehringer Ingelheim Pharma Verwendung von BIBN4096 in Kombination mit anderen Arzneistoffen gegen Migräne für die Behandlung von Migräne
EP1374870A1 (fr) * 2002-06-24 2004-01-02 Rita Dobmeyer Médicament pour la prévention ou le traitement de la migraine
DE10314617A1 (de) * 2003-04-01 2004-10-14 Boehringer Ingelheim Pharma Gmbh & Co. Kg Verwendung des Hydrochlorids der Wirkstoffbase 1-[N2-[3,5-Dibrom-N-[[4-(3,4-dihydro-2(1H)-oxochinazolin-3-yl)-1-piperidinyl]-carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazin in Kombination mit Sumatriptan zur Behandlung von Migräne
CN1812982B (zh) * 2003-06-26 2010-10-27 默沙东公司 苯并二氮杂*cgrp受体拮抗剂

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2005102322A1 *

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Publication number Publication date
JP2007533685A (ja) 2007-11-22
WO2005102322A1 (fr) 2005-11-03
CA2563687A1 (fr) 2005-11-03

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