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EP1663150A2 - Nouvelle poudre pour inhaler contenant l'antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazine - Google Patents

Nouvelle poudre pour inhaler contenant l'antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazine

Info

Publication number
EP1663150A2
EP1663150A2 EP04764021A EP04764021A EP1663150A2 EP 1663150 A2 EP1663150 A2 EP 1663150A2 EP 04764021 A EP04764021 A EP 04764021A EP 04764021 A EP04764021 A EP 04764021A EP 1663150 A2 EP1663150 A2 EP 1663150A2
Authority
EP
European Patent Office
Prior art keywords
active ingredient
powder according
tyrosyl
dibromo
dihydro
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Withdrawn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
EP04764021A
Other languages
German (de)
English (en)
Inventor
Michael Trunk
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 EP1663150A2 publication Critical patent/EP1663150A2/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Withdrawn legal-status Critical Current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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • 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
    • 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

  • the invention relates to powdered preparations for pulmonary or nasal inhalation, comprising the CGRP antagonist 1- [ ⁇ / 2 - [3,5-dibromo- / V - [[4- (3,4-dihydro- 2 (1 - / ) -oxoquinazolin-3-yl) -1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyI) - piperazine (A) or a pharmaceutically acceptable salt thereof, process for their preparation and their use in the manufacture of a medicament for the treatment of headache, migraine and cluster headache.
  • the CGRP antagonist 1 - [/ V 2 - [3,5-dibromo- ⁇ / - [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A) is known from the international patent application PCT / EP9704862 (published as WO 98/11128) and has the following structure:
  • the active ingredient base (A) is a highly effective CGRP antagonist for the acute and prophylactic treatment of headaches, in particular migraines and cluster headache, the application of which is not possible by oral route using classic dosage forms, since the substance has only a low oral bioavailability.
  • an active ingredient to be available systemically as quickly as possible. It should be noted, that the application is straightforward for the patient and no other conditions that can influence the bioavailability (eg "food effect") lead to a restriction of the applicability for the patient. Active ingredients that are to be systemically available are usually administered by oral means Provided that this route cannot be implemented or is desired due to special properties of the active ingredient or special requirements for the application, various other options for the systemic administration of substances have been known in the prior art. In addition to topical applications, its active ingredients can also be used to make it systemically available.
  • Powder inhalation is suitable for substances which have been found to be critical due to their decomposition behavior in solution or which have poor solubility per se represents the absolute amount of the active ingredient that has to be administered in one application, a particular challenge for the formulation.
  • the physical stability e.g. aerodynamic particle size, dispersibility, physicochemical properties
  • the active ingredient proves to be a critical challenge for the development and manufacture of a inhalation powder.
  • inhalation powders which are filled, for example, into suitable capsules (inhalettes), are applied to the lungs by means of powder inhalers.
  • powder inhalers Also known are other systems in which the amount of powder to be applied is predosed (e.g. blister), as well as multidose powder systems.
  • inhalative use can also be carried out by application of suitable powdered inhalation aerosols which are suspended, for example, in HFA134a, HFA227 or their mixture as propellant.
  • the microparticles of a pure active ingredient are passed through the respiratory tract on the surface of the lungs, e.g. applied in the alveoli using the inhalation process. These particles sediment on the surface and can only be absorbed by active and passive transport processes in the body after the dissolution process.
  • Inhalation systems in which the active ingredient is in the form of are known in the literature Solid particles either as a micronized suspension in a suitable solvent system as a carrier or in the form of a dry powder. Powder inhalants, for example in the form of capsules for inhalation, are usually produced on the basis of the general teaching as described in DE-A-179 22 07. A critical factor in such multi-component systems is an even distribution of the drug in the powder mixture.
  • respirable particles inhalable fraction
  • the average particle size of these respirable particles is in the range of a few micrometers, typically between 1 and 10 ⁇ m, preferably below 6 ⁇ m. Such particles are usually generated by micronization (air jet grinding).
  • the suitability of a formulation as a powder inhalative with the active ingredient is only given if a micronizate and an auxiliary (carrier material) with special properties are used, the ratio between active ingredient and auxiliary is in a defined range and a defined amount of powder is available for the application , In addition, special climatic conditions must be observed during the manufacture of the drug.
  • the invention consists in the provision of a novel, stable formulation for the CGRP antagonist 1 - [/ V 2 - [3,5-dibromo- ⁇ / - [[4- (3,4-dihydro-2 (1H) -oxoquinazo - lin-3-yl) -1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine or a physiologically tolerable salt thereof, with the aid of those for which orally non-bioavailable substances sufficient systemic blood levels are generated can.
  • the invention also encompasses the manufacturing process of such formulations and their use in the manufacture of a medicament.
  • the active ingredient base 1- [ ⁇ / 2 - [3,5-dibromo- / V - [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) -1- piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A) and their physiologically tolerable salts in the form of powder mixtures with auxiliaries are physically stable and made sufficiently bioavailable by pulmonary or nasal inhalation can be.
  • micronized active ingredient 1- [ ⁇ / 2 - [3,5-dibromo- ⁇ / - [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) - 1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A), present in its amorphous form, or a physiologically acceptable salt thereof in the formulation of powder mixtures with a physiological harmless, homogeneous excipient has proven to be physically stable.
  • the powder preparations described here enable the powder to be dispersed during inhalation and the active ingredient to be made available for systemic use by such an application.
  • the amorphous state of solids is thermodynamically unstable. In particular, this contributes to the fact that microparticles which have amorphous components or are purely amorphous are metastable with regard to their physicochemical properties.
  • amorphous or partially amorphous active pharmaceutical ingredients and auxiliaries such as sugar, spontaneously recrystallize under normal conditions during their storage time. The process can be accelerated by increasing the air humidity and possibly the temperature. Along with this recrystallization, these particles change their surface properties, their particle morphology and their particle size.
  • the amorphous active ingredient 1- [ ⁇ / 2 - [3,5-dibromo- ⁇ / - [[4- (3,4-dihydro-2 (1H) -oxoquinazolin-3-yl) - 1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A) in the form of the amorphous micronisate produced from it (detection: X-ray crystallographic / x-ray powder diffractometry) use to make a stable inhalable powder Can be found.
  • the amorphous form of the active ingredient is retained over the life of the drug.
  • the acid addition salts are preferably used according to the invention, which are selected, for example, from the group consisting of 1- [ ⁇ / 2 - [3,5-dibromo- / V - [[4- (3,4-dihydro-2 (1 - /) - oxoquinazolin-3-yl) -1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine hydrochloride, sulfate, phosphate, hydrobromide, Carbonate, methanesulfonate, p-toluenesulfonate, nitrate, citrate, malate, tatrate, lactate, succinate, gluconate, acetate, formate, propionate, capronate, oxalate, maleate, Fumarate, mandelate and hydroxysuccinate, the 1-
  • the median value X 5 0 is meant the particle size below which 50% of the particulate aggregate.
  • the micronized active ingredient can be processed in the above ratio with a coarser carrier (e.g. lactose).
  • a coarser carrier e.g. lactose
  • a first object of the present invention is thus an inhalation powder for pulmonary or nasal inhalation use, containing as active ingredient the CGRP antagonist 1- [ ⁇ / 2 - [3,5-dibromo- ⁇ / - [[4- (3,4- dihydro-2 (1H) -oxoquinazolin-3-yl) - 1-piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A) as an active ingredient base or a physiological compatible salt thereof and an inert, homogeneous excipient, characterized in that
  • the parameter X 5 o for the particle size of the active ingredient in the range of from 1 micron to 6 microns, preferably from 1 .mu.m to 3.5 .mu.m, and is
  • the characteristic value Q ( 5 .8) of the active ingredient is at least 60%.
  • normal carrier materials or flow aids can be used as physiologically harmless, homogeneous auxiliaries.
  • the normal carrier materials can be selected from the group consisting of
  • Monosaccharides e.g. glucose or arabinose
  • disaccharides e.g. lactose
  • Starch cellulose derivatives
  • polyalcohols e.g. mannitol, sorbitol, xylitol
  • salts e.g. sodium chloride, calcium carbonate
  • polylactides polyglycolides and mixtures thereof
  • the flow aids can be selected from, for example
  • magnesium stearate Group consisting of magnesium stearate, calcium stearate, stearic acid, stearyl alcohols, calcium behenate, calcium arachinate, hydrogenated vegetable oils such as hydrogenated castor oil or hydrogenated cottonseed oil, fatty acid esters, sodium stearyl fumurate, sodium dodecyl sulfate, magnesium dodecyl sulfate and
  • the inhalable powders according to the invention can be administered, for example, by means of inhalers which dose a single dose from a supply by means of a measuring chamber (for example according to US 4570630A) or via other apparatus (for example according to DE 36 25 685 A).
  • the inhalable powders according to the invention are preferably filled into capsules (to form what are known as inhalers), which are described in inhalers, for example in WO 94/28958 apply.
  • the inhalable powders according to the invention can be obtained according to the procedure described below. Since the active ingredient base (A) and its salts are hygroscopic, certain environmental conditions must be observed when these substances are weighed out. After suitable micronization of the active ingredient, it is conditioned at a defined temperature and air humidity and thus brought into a balance between the water content of the active ingredient and the relative humidity of the environment. The conditioned active ingredient is then mixed in a suitable manner with one or more auxiliaries and the amount of the powder mixture to be applied is dispensed as single doses under defined indoor climate conditions (temperature and air humidity), taking into account the water content of the active ingredient obtained according to these conditions (weight correction). The filling takes place in inhalettes, which are later applied in suitable inhalers. The manufacture of the inhalable powder is then followed by the manufacture of the powder-containing capsules, which have to be end-packaged (blistered) in a suitable manner.
  • a second object of the present invention is thus a method for producing a powder inhalant according to the invention, characterized in that
  • the amount of the powder mixture to be applied is filled into inhalets as individual doses under defined indoor climate conditions.
  • the powder mixture according to the invention can be inhaled, the powder being made available to the patient in a preferred manner in the form of a pre-metered pharmaceutical form.
  • An inhalation capsule system can be mentioned as an example. Systems are also conceivable in which the powder preparation is provided in individual doses, for example in the form of filling blister bowls.
  • the powder preparations described here can be inhaled using a suitable device and thus applied to the lungs.
  • the inhalable powder containing active ingredients that can be produced from such preparations has a particle size which is characterized in that the active ingredient base 1- [ ⁇ / 2 - [3,5-dibromo- ⁇ / - [[4- (3,4-dihydro-2 ( 1H) -oxoquinazolin-3-yl) -1-piperidinyl] carbonyl] -D- tyrosyl] -L-! Ysyl] -4- (4-pyridinyl) -piperazine (A) or their physiologically tolerable salts in the form of microparticles respirable size.
  • powder mixtures are sufficiently easy to process with regard to their cohesive properties in order to reproducibly produce a drug with them. It is thus possible to design a powder preparation for the application of pulmonary (and possibly nasal) inhalation administration in such a way that, on the one hand, when the powder is dispersed during the patient's inhalation process, there is an aerodynamic particle size of the amorphous active ingredient, which after sedimentation after nasal or pulmonary inhalation of the active ingredient in the lungs, and on the other hand the powder (consisting of the micronized active ingredient and a carrier material) is designed such that it can be processed by machine. Sufficient systemic bioavailability of the active substance is obtained by this application of the active substance, which can be achieved by means of this technique, by nasal or pulmonary inhalation in the lungs.
  • a micronisate of the active ingredient base 1- [ ⁇ / 2 - [3,5-dibromo- / V - [[4- (3,4-dihydro-2 (1 H) -oxoquinazolin-3-yl ) -1- piperidinyl] carbonyl] -D-tyrosyl] -L-lysyl] -4- (4-pyridinyl) -piperazine (A), which can be produced, for example, by means of known technology (air jet milling), is only suitable if this in addition to the particle size conditions mentioned above has special properties with regard to the specific surface area of (A) in relation to the surface area of the inert auxiliary of the formulation.
  • the formulation is particularly suitable if the quotient of the specific surface area of the micronizate from (A) to the specific surface area of the inert auxiliary is in each case greater than 0.05, preferably greater, based on the total amount of powder available per application than 0.1, particularly preferably greater than 0.5, very particularly preferably greater than 0.7, and in each case less than 22, preferably less than 15.
  • Micronisates of the active ingredient (A) or a physiologically tolerable salt thereof, which are produced by spray drying, have therefore also proven suitable for such formulations, regardless of whether this spray micronisate as a one-component system or in the form of spray particles consisting of the active ingredient and one or more auxiliaries , is present.
  • Powder preparations which consist of components which meet the above conditions with regard to the particle size of the active ingredient and the ratio of the specific surfaces of the active ingredient to the auxiliary can be processed into homogeneous powder mixtures by known methods and can be filled into capsules or other systems for pre-metering using known methods ,
  • manufacturing steps can only be successfully implemented if the powder is handled in compliance with strict climatic conditions.
  • the maximum temperature difference and the range within which the relative air humidity may fluctuate during the respective production step are decisive for successful production, since the active substance according to the invention is highly hygroscopic.
  • the temperature should not differ by more than ⁇ 5 ° C, preferably ⁇ 3 ° C, and the air humidity by a maximum of ⁇ 15%, by a freely selectable mean.
  • a third object of the present invention is the use of an inhalable powder according to the invention as a medicament, in particular for the production of a medicament for the treatment of headaches, migraines or cluster headaches.
  • a fourth object of the present invention comprises the use of an inhalable powder according to the invention for the manufacture of a capsule (inhalette).
  • a capsule inhaler
  • Such a capsule (inhaler) is characterized by a filling amount of 2 to 50 mg of inhalable powder according to the invention.
  • Measurement method To determine the particle size, the powder is fed to a laser diffraction spectrometer using a dispersing unit.
  • median value X 5 o refers to the particle size below which 50% of the particulate aggregate.
  • the Q ⁇ 5 ⁇ ) value describes the percentage of particles that have a size below 5.8 ⁇ m.
  • Measuring device Laser diffraction spectrometer (HELOS), Sympatec software: WINDOX version 3.3 / REL 1 dispersing unit: RODOS / dispersing pressure: 3 bar focal length: 100 mm [measuring range: 0.9 175 ⁇ m] Evaluation mode: HRLD (V 3.3 Rel. 1)
  • Measurement method The specific surface is determined by exposing the powder sample to a nitrogen atmosphere at different pressures. By cooling the sample, the nitrogen molecules condense on the surface of the particles. The amount of condensed nitrogen is determined via the pressure drop in the system and the specific surface area of the sample is calculated using the area required by nitrogen and the sample weight. Measuring device Tri Star Multi Point BET, Micromeritics heating station: VacPrep 061, Micromeritics heating: approx. 12h / 40 ° C
  • Sample container 1/2 inch; with "filier rod” analysis method: 10 point BET surface determination 0.1 to 0.20 p / pO absolute pressure tolerance: 5.0 mm Hg rel. Pressure tolerance: 5.0% Evacuation speed: 50.0 mm Hg / second Evacuation threshold: 10.0 mm Hg Evacuation time: 0.1 h Empty volume: Dewar vessel lowering, t: 0.5 h Equilibration time: 20 seconds Equilibrium time: 600 seconds
  • Adsorbent Nitrogen 2) Examples
  • a) 50 g (water-free) air-jet-ground active ingredient with a specific surface area of 20.2 m 2 / g are conditioned at 25 ° C. and 45% relative atmospheric humidity for 8 hours and with 450 g Pharmatose ® 200M (manufacturer: Danone), specific surface area 0.96 m 2 / g, mixed (layered sieving, Turbula mixer).
  • the filling takes place in individual capsules under the same room conditions as the provision of the starting materials and mixing of the individual components.
  • a filling of 20.12 mg of the powder mixture of the above composition corresponds to a micronized active ingredient content per capsule of 2 mg (anhydrous).
  • the filling takes place in individual capsules under the same room conditions as the provision of the starting materials and mixing of the individual components.
  • a filling of 51 mg of the powder mixture of the above composition corresponds to a micronized active ingredient content per capsule of 25 mg (anhydrous).

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

Abstract

Compositions pulvérulentes pour l'inhalation pulmonaire ou nasale, qui contiennent l'antagoniste de CGRP 1-[N<2>-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-pipéridinyl]carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-pipérazine (A) ou un sel acceptable sur le plan pharmaceutique dudit composé. La présente invention concerne également des procédés de préparation desdites compositions ainsi que leur utilisation pour la fabrication d'un médicament destiné à traiter les céphalées, la migraine et l'algie vasculaire de la face.
EP04764021A 2003-08-18 2004-08-12 Nouvelle poudre pour inhaler contenant l'antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazine Withdrawn EP1663150A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10338407A DE10338407A1 (de) 2003-08-18 2003-08-18 Neue Inhalationspulver enthaltend den 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
PCT/EP2004/009017 WO2005018604A2 (fr) 2003-08-18 2004-08-12 Nouvelle poudre à inhaler contenant l'antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-pipéridinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-pipérazine

Publications (1)

Publication Number Publication Date
EP1663150A2 true EP1663150A2 (fr) 2006-06-07

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EP04764021A Withdrawn EP1663150A2 (fr) 2003-08-18 2004-08-12 Nouvelle poudre pour inhaler contenant l'antagoniste de cgrp 1-[n2-[3,5-dibromo-n-[[4-(3,4-dihydro-2(1h)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)-piperazine

Country Status (5)

Country Link
EP (1) EP1663150A2 (fr)
JP (1) JP2007502791A (fr)
CA (1) CA2536050A1 (fr)
DE (1) DE10338407A1 (fr)
WO (1) WO2005018604A2 (fr)

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DE10338399A1 (de) * 2003-08-18 2005-03-17 Boehringer Ingelheim Pharma Gmbh & Co. Kg Mikropartikel, enthaltend den CGRP-Antagonisten 1-[N2-[3,5-Dibrom-N-[[4-(3,4-dihydro-2(1H)-oxochinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-L-Iysyl]-4-(4-pyridinyl)-piperazin, Verfahren zu deren Herstellung sowie deren Verwendung als Inhalaltionspulver
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DE102006030166A1 (de) * 2006-06-29 2008-01-10 Boehringer Ingelheim Pharma Gmbh & Co. Kg Tempern

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CA2536050A1 (fr) 2005-03-03
WO2005018604A3 (fr) 2005-07-21

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