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EP1833483A1 - Utilisation d'antagonistes de cgrp selectionnes pour lutter contre des bouffees de chaleur menopausiques - Google Patents

Utilisation d'antagonistes de cgrp selectionnes pour lutter contre des bouffees de chaleur menopausiques

Info

Publication number
EP1833483A1
EP1833483A1 EP05823294A EP05823294A EP1833483A1 EP 1833483 A1 EP1833483 A1 EP 1833483A1 EP 05823294 A EP05823294 A EP 05823294A EP 05823294 A EP05823294 A EP 05823294A EP 1833483 A1 EP1833483 A1 EP 1833483A1
Authority
EP
European Patent Office
Prior art keywords
oxo
piperidine
tetrahydro
piperidin
carboxylic acid
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Withdrawn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
EP05823294A
Other languages
German (de)
English (en)
Inventor
Klaus Rudolf
Henri Doods
Stephan Georg Mueller
Annette Zamponi
Philipp Lustenberger
Dirk Stenkamp
Kirsten Arndt
Gerhard Schaenzle
Rolf-Stefan Brickl
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
Boehringer Ingelheim Pharmaceuticals Inc
Original Assignee
Boehringer Ingelheim International GmbH
Boehringer Ingelheim Pharma GmbH and Co KG
Boehringer Ingelheim Pharmaceuticals Inc
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
Application filed by Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH and Co KG, Boehringer Ingelheim Pharmaceuticals Inc filed Critical Boehringer Ingelheim International GmbH
Publication of EP1833483A1 publication Critical patent/EP1833483A1/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Withdrawn legal-status Critical Current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
    • A61K31/495—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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones

Definitions

  • Hot flashes are a common symptom of the post-menopausal syndrome, whose physiology is still poorly understood. Apart from the hormone replacement therapy, which is a complex intervention and often can not be applied permanently due to the associated side effects, so far there is no simple, low-side-effect therapy for this generally annoying perceived appearance.
  • Hot flashes are caused by vascular dilation and increased blood flow.
  • CGRP calcium phosphate
  • the present invention thus relates to the use of selected CGRP antagonists, their physiologically acceptable salts or the hydrates of the salts for combating menopausal hot flashes, including both prevention and acute treatment.
  • the use according to the invention preferably relates to monotherapy with an individual substance, but also excludes the combination therapy with a plurality of substances of said active substance. group.
  • the use according to the invention can be carried out in addition to a hormone substitution usually carried out.
  • CGRP antagonists the following compounds are suitable for combating menopausal hot flashes, for producing a corresponding medicament and as a constituent of a corresponding medicament.
  • the dosage required to achieve a corresponding effect is expediently from 0.0001 to 3 mg / kg body weight, preferably 0.01 to 1 mg / kg body weight, given by intravenous or subcutaneous administration, 0.01 to 20 mg / kg body weight, preferably 0.1 to 20 mg / kg when given orally Body weight, and by nasal or inhalation administration 0.01 to 10 mg / kg body weight, preferably 0.1 to 10 mg / kg body weight, in each case one to three times daily.
  • the dosage may then be 1/5 of the lower limits specified above to 1/1 of the above limits.
  • the selected CGRP antagonists, their physiologically acceptable salts or the hydrates of the salts together with one or more inert customary carriers and / or diluents for example with corn starch, lactose, cane sugar, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, Tartaric acid, water, water / ethanol, water / glycerol, water / sorbitol, water / polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethyl cellulose or fatty substances such as hard fat or their suitable mixtures, in conventional pharmaceutical preparations such as tablets, dragees, Incorporate capsules, powders, suspensions, solutions, metered aerosols or suppositories.
  • aqueous solution for nasal administration with 5 mg active ingredient, or
  • CGRP is released by sensory nerves, such as the trigeminal nerve, which innervates part of the facial skin. Stimulation of trigeminal ganglion in humans has been shown to increase plasma CGRP levels and cause reddening of the skin ([4]: PJ Goadsby et al., Annais of Neurology, Vol. 23, No. 2, 1988, 193-196 ).
  • the following examples describe pharmaceutical dosage forms containing as active ingredient one of the selected CGRP antagonists for use according to the invention.
  • the selected CGRP antagonists (A) may be administered, for example, using one of the following pharmaceutical formulations:
  • Pellets for capsules containing varying parts by weight (A);
  • Extrudates for capsules or tablets containing varying parts by weight (A);
  • the following examples describe pharmaceutical preparations containing as active substance one of the CGRP antagonists selected according to the invention, a physiologically acceptable salt thereof or a hydrate of the salt.
  • the first is a table in which the drug components are assigned numbers, which serve in the following example tables for the identification of the active ingredients.
  • composition / tablet Composition / tablet:
  • CGRP antagonist and lactose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with an aqueous povidone solution; The granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 1.1 mm. Then the granules are mixed for 5 minutes with crospovidone and then another 1 minute with magnesium stearate. The mixture thus obtained is pressed in a tablet press into tablets of a suitable diameter.
  • a suitable mixer eg Diosna P2
  • lactose fine
  • composition / tablet Composition / tablet:
  • CGRP antagonist and lactose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with an aqueous povidone solution; The granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 1.1 mm. The granules are then mixed with crospovidone for 5 minutes and then with magnesium stearate for 1 minute. The mixture thus obtained is pressed in a tablet press into tablets of a suitable diameter.
  • a suitable mixer eg Diosna P2
  • lactose fine
  • composition / tablet Composition / tablet:
  • CGRP antagonist and lactose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with an aqueous povidone solution; The granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 1.1 mm. The granules are then mixed with crospovidone for 5 minutes and then with magnesium stearate for 1 minute. The mixture thus obtained is pressed in a tablet press into tablets of a suitable diameter.
  • a suitable mixer eg Diosna P2
  • lactose fine
  • composition / tablet Composition / tablet:
  • CGRP antagonist and lactose are homogeneously mixed in a suitable mixer (eg Diosna P2). Subsequently, the mixture is granulated with an aqueous povidone solution. The granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 1.1 mm. Then the granules are mixed for 5 minutes with crospovidone and then another 1 minute with magnesium stearate. The mixture thus obtained is pressed in a tablet press into tablets of a suitable diameter.
  • Composition CGRP antagonist 100 mg Lactose 284 mg microcrystalline cellulose 89.5 mg
  • CGRP antagonist, lactose (fine) and microcrystalline cellulose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with water.
  • the granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 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 of a suitable diameter.
  • CGRP antagonist, lactose (fine) and microcrystalline cellulose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with water.
  • the granules are mixed with a Kressner sieve 1.6 mm sieved and dried for 2 hours at 40 0 C. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 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 of a suitable diameter.
  • CGRP antagonist, lactose (fine) and microcrystalline cellulose are homogeneously mixed in a suitable mixer (eg Diosna P2); then the mixture is granulated with water.
  • the granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours. Subsequently, the granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 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 of a suitable diameter.
  • CGRP antagonist, lactose (fine) and microcrystalline cellulose are homogeneously mixed in a suitable mixer (eg Diosna P2); and then granulated the mixture with water.
  • the granules are sieved with a 1.6 mm Kressner sieve and dried at 40 ° C. for 2 hours.
  • the dry granules are sieved in a suitable mill, for example a Comill at 3000 rev / min with mesh size 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 of a suitable diameter.
  • the active ingredient is dissolved in water with stirring and optionally heating.
  • the isotonan mannitol is added and the solution is made up to the final volume with water.
  • the active ingredient is dissolved in water with stirring and optionally heating.
  • the isotonan mannitol is added and the solution is made up to the final volume with water.
  • the active ingredient is dissolved in water with stirring and optionally heating.
  • the isotonan mannitol is added and the solution is made up to the final volume with water.
  • the active ingredient is dissolved in water with stirring and optionally heating.
  • the isotonan mannitol and Labrasol are added and the solution is made up to the final volume with water.
  • Aqueous solution for intranasal administration containing 50% CGRP antagonist and 1.5% Labrasol
  • the active ingredient is dissolved in water with stirring and optionally heating.
  • the isotonan mannitol and Labrasol are added and the solution is made up to the final volume with water.
  • the medicaments of the invention may also be in the form of small particles, e.g. Pellets are produced.
  • the active ingredient can be applied to neutral pellets consisting of sucrose and starch or microcrystalline cellulose.
  • Composition Povidone K25 3 parts by weight microcryst. Cellulose 20 parts by weight meglumine 77 parts by weight
  • the core material is fractionated on a tumble screening machine with different sieve trays with nominal mesh sizes of 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • the active substance-containing pellets are screened with a sieve with a nominal mesh size of 1.25 mm.
  • the good fraction (grain size ⁇ 1.25 mm) is further processed.
  • the structure of the drug layer is generally always in the same way, but the active ingredient and amount, binder type and amount, amount of talc and water, isopropanol or ethanol amount are varied.
  • Composition core material 100 parts by weight
  • the active substance-containing pellets are screened with a sieve with a nominal mesh size of 1.25 mm.
  • the good fraction (grain size ⁇ 1.25 mm) is widened / elaborated.
  • the structure of the drug layer is generally in always the same way, but
  • Type of active ingredient and amount type of binder and amount, amount of talc and water,
  • Isopropanol or ethanol amount can be varied.
  • CGRP antagonist either as an active form, in the form of a physiologically acceptable salt or in the form of the
  • the active substance-containing pellets contain one of the active ingredients 1-22)
  • composition Active substance containing pellets 30 parts by weight
  • the isolated core material is then in a convection oven at 40 0 C over
  • the dried retarded pellets are sieved with a sieve of nominal mesh size 1.5 mm.
  • the medicaments according to the invention can also be prepared in the form of extrudates which, after cutting / spheronizing, are filled directly into capsules or processed into tablets after grinding.
  • the production takes place in the following steps: 1. extrusion
  • composition Povidone K25 6 parts by weight
  • CGRP antagonist 100 parts by weight of CGRP antagonist, 40 parts by weight of microcrystalline cellulose (Avicel PH 101) and 6 parts by weight of povidone (Kollidon K25) are mixed in a Rhönrad mixer for 15 minutes. Then, the powder mixture is introduced into a twin-screw extruder together with water, which is added with a metering pump at a rate of about 1 kg / h. The water dosage is automatically controlled so that a target torque of approx. 19% is generated in the extruder. The extrusion takes place via a nozzle plate with holes of 0.8 mm diameter.
  • the pellets are dried at 8O 0 C for about 1.5 hours in a fluidized bed dryer.
  • the core material is fractionated by a tumble screening machine with different sieve trays with nominal mesh sizes from 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • the extrusion of the extrudates into pellets takes place in a spheronizer, with approx. 3 minutes rounded to approx. 850 RPM.
  • the pellets are dried at 80 ° C for about 1.5 hours in a fluidized bed dryer.
  • the core material is fractionated on a tumble screening machine with different sieve trays with nominal mesh sizes of 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • CGRP antagonist 400 parts by weight of CGRP antagonist, 110 parts by weight of microcrystalline cellulose (Avicel PH 101) and 15 parts by weight of povidone (Kollidon K25) are mixed in a Rhönrad mixer for 15 minutes. Then, the powder mixture is introduced into a twin-screw extruder together with water, which is added with a metering pump at a rate of about 1 kg / h. The water dosage is automatically controlled so that a target torque of approx. 19% is generated in the extruder. The extrusion takes place via a nozzle plate with holes of 0.8 mm diameter.
  • the pellets are dried at 8O 0 C for about 1.5 hours in a fluidized bed dryer.
  • the core material is fractionated on a tumble screening machine with different sieve trays with nominal mesh sizes of 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • This manufacturing method is the basis of other combination examples listed in the following table.
  • composition Povidone K25 6 parts by weight Poloxamer 40 parts by weight CGRP antagonist 100 parts by weight
  • CGRP antagonist 100 parts by weight of CGRP antagonist, 40 parts by weight of Poloxamer and 6 parts by weight of Povidon K25 are mixed in a Rhönrad mixer for 15 minutes. Then the powder mixture is introduced at a rate of about 1 kg / h together with water, which is added with a metering pump, in a twin-screw extruder. The temperature is controlled so that a setpoint torque of approx. 19% is generated in the extruder. The extrusion takes place via a nozzle plate with holes of 0.8 mm diameter.
  • the exiting extruded strands are cut with a top mark, the rounding of the extrusion strands into pellets is carried out in a spheronizer, wherein about 3 minutes at about 850 RPM at about 40 0 C is rounded. Drying of the pellets at 80 ° C. for approx. 1.5 hours in a fluidized-bed dryer.
  • the core material is fractionated on a tumble screening machine with different sieve trays with nominal mesh sizes of 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • the exiting extruded strands are cut with a top mark, the rounding of the extrusion strands into pellets is carried out in a spheronizer, wherein about 3 minutes at about 850 RPM at about 40 0 C is rounded. Drying of the pellets at 80 ° C. for approx. 1.5 hours in a fluidized-bed dryer.
  • the core material is fractionated by a tumble screening machine with different sieve trays with nominal mesh sizes from 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • composition Povidone K25 18 parts by weight Poloxamer 132 parts by weight CGRP antagonist 400 parts by weight
  • CGRP antagonist 400 parts by weight of CGRP antagonist, 132 parts by weight of Poloxamer and 18 parts by weight of Povidon K25 are mixed in a Rhönrad mixer for 15 minutes. Then the powder mixture is introduced at a rate of about 1 kg / h together with water, which is added with a metering pump, in a twin-screw extruder. The temperature is controlled so that a setpoint torque of approx. 19% is generated in the extruder. The extrusion takes place via a nozzle plate with holes of 0.8 mm diameter.
  • the exiting extruded strands are cut with a top mark, the rounding of the extrusion strands into pellets is carried out in a spheronizer, wherein about 3 minutes at about 850 RPM at about 40 0 C is rounded. Drying of the pellets at 80 ° C. for approx. 1.5 hours in a fluidized-bed dryer.
  • the core material is fractionated on a tumble screening machine with different sieve trays with nominal mesh sizes of 0.71 to 1.25 mm.
  • the respectively suitable material fractions between 0.71 and 0.90 or 0.90 and 1.12 mm are used in the further processes.
  • compositions may vary, further examples being shown in tabular form below.
  • Granules are further processed with conventional tableting excipients analogous to Example 1 to give tablets.
  • the spray thus obtained is dried with the aid of a drying gas with an inlet temperature between 13O 0 C and 200 0 C and a starting temperature of 40 0 C to 120 0 C while the volume flow of the spray gas 1 Nm 3 Zh to 15 Nm 3 Zh and the flow rate of drying gas 15 Nm 3 Zh to 150 Nm 3 Zh.
  • the dried solids content is collected by mass separator and filter unit.
  • 1 capsule for powder inhalation contains: CGRP antagonist 0.5 mg lactose 20 mg
  • the CGRP antagonist is prepared as a spherical nanostructured drug particles and mixed homogeneously with lactose. The mixture is packed in hard gelatin capsules.
  • Composition CGRP antagonist 0.5 mg physiological saline
  • the active ingredient is dissolved in physiological saline.
  • the dose levels may vary and are shown in tabular form below.
  • the examples contain 0.2 to 30 mg CGRP antagonist.
  • Table for Example 9
  • Composition CGRP antagonist 200 mg hard wax ad 2 g
  • the hard wax is melted and the active ingredient is suspended in the mass. Subsequently, the mass is poured into suitable suppository forms.
  • the dose levels may vary and are shown in tabular form below.
  • the examples contain 50 to 600 mg of CGRP antagonist.

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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)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne l'utilisation d'antagonistes de CGRP sélectionnés, de leurs sels physiologiquement compatibles ou des hydrates de ces sels pour lutter contre des bouffées de chaleur ménopausiques, ainsi que des médicaments correspondants qui contiennent un ou plusieurs des antagonistes de CGRP sélectionnés comme ingrédient actif et la production de ceux-ci.
EP05823294A 2004-12-29 2005-12-23 Utilisation d'antagonistes de cgrp selectionnes pour lutter contre des bouffees de chaleur menopausiques Withdrawn EP1833483A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102004063752A DE102004063752A1 (de) 2004-12-29 2004-12-29 Verwendung ausgewählter CGRP-Antagonisten zur Bekämpfung menopausaler Hitzewallungen
PCT/EP2005/013972 WO2006072415A1 (fr) 2004-12-29 2005-12-23 Utilisation d'antagonistes de cgrp selectionnes pour lutter contre des bouffees de chaleur menopausiques

Publications (1)

Publication Number Publication Date
EP1833483A1 true EP1833483A1 (fr) 2007-09-19

Family

ID=35734403

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05823294A Withdrawn EP1833483A1 (fr) 2004-12-29 2005-12-23 Utilisation d'antagonistes de cgrp selectionnes pour lutter contre des bouffees de chaleur menopausiques

Country Status (6)

Country Link
US (2) US20060142274A1 (fr)
EP (1) EP1833483A1 (fr)
JP (1) JP2008525510A (fr)
CA (1) CA2594097A1 (fr)
DE (1) DE102004063752A1 (fr)
WO (1) WO2006072415A1 (fr)

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US7595312B2 (en) * 2002-10-25 2009-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Selected CGRP antagonists, processes for preparing them and their use as pharmaceutical compositions
DE102004015723A1 (de) * 2004-03-29 2005-10-20 Boehringer Ingelheim Pharma Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102005038831A1 (de) * 2005-08-17 2007-02-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
MX2008015562A (es) * 2006-06-08 2008-12-17 Boehringer Ingelheim Int Tratamiento de trastornos gastrointestinales con antagonistas de cgrp.
TW201244733A (en) * 2011-03-31 2012-11-16 Shiseido Co Ltd Hot flash suppressant

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DE19937304C2 (de) * 1999-08-10 2003-08-21 Boehringer Ingelheim Pharma Verwendung von CGRP-Antagonisten zur Bekämpfung menopausaler Hitzewallungen
US6521609B1 (en) * 1999-08-10 2003-02-18 Boehringer Ingelheim Pharma Kg Use of CGRP antagonists and CGRP release inhibitors for combating menopausal hot flushes
US7595312B2 (en) * 2002-10-25 2009-09-29 Boehringer Ingelheim Pharma Gmbh & Co. Kg Selected CGRP antagonists, processes for preparing them and their use as pharmaceutical compositions
DE10250080A1 (de) * 2002-10-25 2004-05-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE10250082A1 (de) * 2002-10-25 2004-05-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102004015723A1 (de) * 2004-03-29 2005-10-20 Boehringer Ingelheim Pharma Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102004018795A1 (de) * 2004-04-15 2005-10-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
US7696195B2 (en) * 2004-04-22 2010-04-13 Boehringer Ingelheim International Gmbh Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions
DE102004019492A1 (de) * 2004-04-22 2005-11-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel

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Also Published As

Publication number Publication date
US20060142274A1 (en) 2006-06-29
DE102004063752A1 (de) 2006-07-13
WO2006072415A1 (fr) 2006-07-13
US20080176836A1 (en) 2008-07-24
JP2008525510A (ja) 2008-07-17
CA2594097A1 (fr) 2006-07-13

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