WO2010070090A1 - Feste zusammensetzung mit dem wirkstoff rasagilin - Google Patents
Feste zusammensetzung mit dem wirkstoff rasagilin Download PDFInfo
- Publication number
- WO2010070090A1 WO2010070090A1 PCT/EP2009/067508 EP2009067508W WO2010070090A1 WO 2010070090 A1 WO2010070090 A1 WO 2010070090A1 EP 2009067508 W EP2009067508 W EP 2009067508W WO 2010070090 A1 WO2010070090 A1 WO 2010070090A1
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- WO
- WIPO (PCT)
- Prior art keywords
- active ingredient
- solid composition
- composition according
- rasagiline
- pharmaceutically acceptable
- Prior art date
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Classifications
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- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the present invention relates to a solid composition containing at least one pharmaceutically acceptable excipient and, as an active ingredient, rasagiline or a pharmaceutically acceptable salt thereof.
- the invention further relates to a process for the preparation of this solid composition and to a pharmaceutical composition containing this solid composition.
- Rasagiline the R (+) - enantiomer of N-propargyl-1-aminoindan
- US Pat. No. 5,532,415 discloses the manufacture of rasagiline and various salts of this compound as well as the use of the drug for the treatment of a variety of diseases such as Parkinson's, memory disorders, dementia, depression, schizophrenia, hyperactivity, etc.
- Another method for the production of Salts of rasagiline is disclosed in WO 2002/068376.
- rasagiline is disclosed in EP-A-0 436 492 which discloses rasagiline and generally pharmaceutically acceptable acid addition salts thereof, specifically the hydrochloride and tartrate of rasagiline.
- Further salts of rasagiline are described in WO 95/11016, namely the sulfate, phosphate, mesylate, maleate, esylate, acetate, fumarate, hydrobromide, tosylate and benzoate.
- Further acid addition salts of rasagiline are described in WO 2008/019871.
- Active ingredients are often mixed in pharmaceutical formulations in finely ground form as a powder with various adjuvants and optionally compressed after granulation to tablets.
- the physical form of the active substance ie the polymorphic or amorphous form
- the active ingredient mix well with the auxiliaries used and can be further processed.
- a uniform distribution within the amounts of excipients used is necessary to ensure that, for example, tablets produced from the mixture each contain the same amount of active substance.
- WO 2008/131961 which provides adsorbates which contain, in addition to a pharmaceutically acceptable, water-soluble, organic active ingredient, a pharmaceutically acceptable salt of rasagiline in amorphous form, deals with the problem of the stability of the physical form of the active substance rasagiline.
- the adsorbates are prepared by spray-drying a solution of active ingredient and excipient. As a result, the active ingredient is adsorbed on the excipient particles, so that separate active and auxiliary phases are present.
- WO 2006/091657 deals with the second problem of the homogeneous distribution of active ingredient particles in excipient mixtures.
- a particularly uniform distribution of the active ingredient particles in an adjuvant mixture is achieved by milling the pharmaceutically acceptable salt of rasagiline such that more than 90% of the volume of the active ingredient particles has a size of less than 250 ⁇ m.
- micronized drug particles have the disadvantage that it may come during grinding and further processing to electrostatic charging and agglomeration.
- micronized active ingredients have a reduced flowability, so that this can lead to problems during further processing.
- the form should optionally be able to process with other excipients easily to drugs and thereby ensure a uniform distribution of the drug and thus the uniformity of the active substance content in the drug.
- the active ingredient form in the finished drug during the storage time in particular be physically stable.
- the present invention thus relates to a solid composition containing at least one pharmaceutically acceptable excipient and, as an active ingredient, rasagiline or a pharmaceutically acceptable salt thereof, characterized in that the excipient and the active ingredient are present in a homogeneous, molecularly disperse mixture.
- a homogeneous mixture is understood as meaning a solid solution of the active ingredient in the excipient.
- the solid composition thus has only one phase, wherein the dissolved active ingredient is uniformly distributed in the excipient.
- the homogeneous mixture thus contains at least substantially no phases of pure excipient or pure active ingredient.
- the excipient and active ingredient are rather mixed together at the molecular level, so that neither visually nor with other physical methods phase boundaries between auxiliary and active substance can be observed. Accordingly, the active ingredient in the solid composition according to the invention is also present in neither crystalline nor amorphous form. The active ingredient is rather distributed at the molecular level between the molecules of the excipient.
- the active substance can therefore no longer be detected by, for example, X-ray powder diffractograms but by spectroscopic methods such as, for example, confocal Raman spectroscopy.
- pellets are produced from the samples, on the smooth surface of which a confocal mapping can be carried out.
- the mappings are carried out in an area of 10 ⁇ m x 10 ⁇ m.
- a NT-MDT NTEG RA-Spektra Nanofinder
- Raman spectrometer with a maximum lateral resolution of ⁇ x, ⁇ y ⁇ 400 nm, height resolution ⁇ z ⁇ 700 nm, laser excitation 488 nm (Ar laser), 632.8 nm (HeNe laser).
- the detector used is a PMT (photomultiplier tube).
- the present invention also encompasses those solid compositions which still contain small amounts of undissolved drug particles. Such small amounts of undissolved particles do not disturb the advantageous properties of the composition according to the invention. In the solid composition, however, should less than 15 wt .-%, preferably less than 10 wt .-%, more preferably less than 5 wt .-% and particularly preferably less than 1 wt .-% of the total amount of the active ingredient in the form of particles.
- composition according to the invention particularly preferably contains no active substance particles, in particular no active substance particles, which can be observed visually, for example under a light microscope, due to the phase boundaries between the active substance and the adjuvant occurring.
- the solid composition according to the invention should therefore show a completely homogeneous image on visual inspection, in which no phase boundaries can be recognized.
- the active ingredient is evenly distributed in the adjuvant and thus "prediluted".
- the composition thus obtained can be processed either directly or, for example, with other excipients easily to drugs.
- the composition of the invention allows a uniform mixing with other excipients, without a complex micronization would be necessary.
- prediluting the active ingredient a homogeneous distribution in pharmaceutical formulations prepared therefrom and hence uniformity of the active ingredient content of these formulations are ensured. This facilitates, for example, the production of 200 mg tablets containing only 1 mg of rasagiline.
- Another advantage of the composition of the invention is that the molecular disperse distribution of the active ingredient in the excipient accelerates the dissolution of the active ingredient. This may be important, for example, if a rasagiline salt which is sparingly soluble in water or at least less soluble, for example rasagiline tartrate, is used.
- the amount of the active ingredient in the solid composition of the present invention is not particularly limited. Rather, it depends on the one hand on the desired dilution effect and on the other hand on the solubility of the active ingredient in the selected excipient.
- the composition according to the invention may contain from 0.5% to 25% by weight of active ingredient, calculated as the free base, based on the total weight of auxiliary and active substance.
- the composition of the invention contains 5 wt .-% to 15 wt .-% active ingredient, calculated as the free base based on the total weight of auxiliary and active ingredient.
- any pharmaceutically acceptable excipient capable of producing a homogeneous, molecularly disperse mixture with rasagiline or the like can be selected selected pharmaceutically acceptable salt thereof.
- the excipient must thus be able to dissolve the active ingredient in the desired concentration.
- auxiliaries are, for example, polymers, copolymers, saccharides, oligosaccharides, polysaccharides and sugar alcohols.
- auxiliaries have proven to be particularly suitable: sucrose, sorbitol, xylitol, Eudragit, polyethylene glycol (PEG, for example PEG 4000 or PEG 20000), polyoxyethylene glycol monostearate, glycerol polyethylene glycol ricinolate, macrogol glycerol stearate (eg Gelucire),
- Glycerol palmitole stearate eg Precirol
- Macrogolglycerollaurat eg Gelucire 50
- Polyethylenglykolcetylstearylether eg Cremophor A25
- Glycerolmonostearat eg Imwitor
- polyvinylpyrrolidone PVP, for example PVP 30 or Kollidon VA64
- methacrylates cellulose derivatives, such as cellulose ethers (for example Methocel K4M CR Premium ), Methyl cellulose (MC), hydroxypropyl cellulose (HPC, for example HPC HF) and hydroxypropylmethyl cellulose (HPMC, for example HPMC 615), and copolymers such as copovidone (from vinyl acetate and vinyl pyrrolidone) or Pluronic, eg Pluronic F68, a block copolymer of ethylene oxide and propylene oxide.
- Pluronic eg Pluronic F68
- composition of the invention may contain an adjuvant or a mixture of two or more adjuvants.
- the solid compositions of the invention can be prepared by mixing the excipient and the active ingredient to give a homogeneous, molecularly dispersed mixture.
- a corresponding mixing in a common melt of auxiliary and active ingredient preferably by melt extrusion, take place.
- the mixing takes place by dissolving auxiliaries and active substance in a solvent and then evaporating off the solvent.
- care must be taken that the auxiliary and the active ingredient do not precipitate side by side but form the desired homogeneous, molecularly disperse mixture.
- the evaporation step may be slow over a longer period of time, for example at least 24 hours, preferably in a period of for example 24 hours to 150 hours, in particular in a period of 72 hours to 120 Hours.
- a solvent any solvent can be used which is able to solve both the active ingredient and the excipient.
- water or a mixture of water and ethanol for example, about 20 vol.% To 30 vol.% Aqueous ethanol solution is suitable.
- the solution may be acidified with, for example, an inorganic or organic acid such as hydrochloric acid, acetic acid, formic acid, benzoic acid, citric acid, malic acid, tartaric acid, oxalic acid, fumaric acid, succinic acid, maleic acid and salicylic acid.
- hydrochloric acid and citric acid, especially citric acid are preferred acids.
- the solution onto, for example, inert excipient particles, so-called nonpareils.
- the spraying can take place, for example, in a fluidized-bed granulator.
- the auxiliary and active substance are separated from the solution together as a homogeneous, molecularly disperse mixture.
- the solid composition according to the invention can be further processed into a pharmaceutical, in particular a solid dosage form, by conventional methods known to those skilled in the art.
- a pharmaceutical in particular a solid dosage form
- This is preferably a capsule, tablet, orally disintegrating tablet, sustained-release tablet, pellets or granules. Preference is given to tablets which are prepared by direct compression with the auxiliaries customarily used for this purpose.
- the pharmaceutical composition containing the solid composition according to the invention is in particular in the form of a tablet containing from 0.2% to 20% by weight of active ingredient, from 40% to 95% by weight of one or more bulking agents Wt .-% to 30 wt .-% of one or more disintegrants and 0 wt .-% to 5 wt .-% of one or more lubricants, each based on the total weight of the drug without any existing coatings.
- Corresponding drugs have an excellent uniformity of the content, as can not be achieved in particular in tablets with direct compression, in particular at low active ingredient content of ⁇ 5 wt .-%, usually.
- Rasagiline tartrate based on 10 g of the free base, was mixed with 100 g of a polymer or sugar alcohol in a Petri dish and heated in a heating oven at 150 0 C until melted (about 1 h).
- the products were analyzed visually, ie by light microscopy and with the naked eye (for homogeneity) and by means of HPLC (active ingredient content and impurities).
- Sorbitol, PEG 4000, glycerol palmitole stearate (Precirol), macrogol glycerol laurate (Gelucire 50), PEG cetyl stearyl ether (Cremophor A25) and glyceryl monostearate (Imwitor) proved to be particularly suitable solvents.
- the melts prepared with these excipients also proved to be stable (visual and HPLC) after four weeks storage at 40 ° C. and 75% relative humidity.
- Rasagihntartrat based on 50 g of the free base, was mixed with 500 g of PEG in a free-radical mixer (Turbula TB10) for 15 min and extruded in a twin-screw extruder (Leistritz Micro 18), with several heatable cylinders along the screw individually at increasing temperatures of 20 0 C to 65 0 C were set. The resulting extrudate was cooled to room temperature and ground to particles having an average size of 800 to 1000 ⁇ m.
- Rasagiline tartrate based on 100 g of the free base, was mixed with 500 g Gelucire in a tumbler (Turbula TB10) for 15 min and extruded in a twin screw extruder (Leistritz Micro 18), with several heatable cylinders along the screw individually at increasing temperatures of 25 ° C to 100 0 C were set.
- Excipient and rasagiline were mixed in a weight ratio of 10: 1 in a petri dish or beaker. Purified water was added to the solid mixture and the whole was added to a solution (about 2 h) until complete dissolution Stirred magnetic stirrer. Subsequently, the solution was dried in a vacuum oven at 30 0 C and 0.1 bar for 72 h. The products were analyzed visually, ie by light microscopy and with the naked eye (for homogeneity) and by means of HPLC (active ingredient content and impurities). Sorbitol proved to be a particularly suitable excipient. The solid solutions prepared with sorbitol were found to be stable (visual and HPLC) after four weeks storage at 40 ° C and 75% humidity.
- Excipient and rasagiline were mixed in a weight ratio of 10: 1 and 2: 1, respectively, in a petri dish or beaker.
- a 30% (by volume) aqueous ethanol solution was added to the solid mixture and the whole was stirred on a magnetic stirrer until complete (about 2 hours).
- the solution was dried in a vacuum oven at 40 0 C and 0.1 bar for 120 h.
- the products were analyzed visually, ie by light microscopy and with the naked eye (for homogeneity) and by means of HPLC (active ingredient content and impurities).
- auxiliaries proved to be PVP 30, HPMC 615 and Kollidon VA 64 in the weight ratio 2: 1, PEG 20000, HPC HF and Pluronic F68 in a weight ratio of 10: 1 and Methocel K4M CR Premium and PEG 4000 in both weight ratios.
- the solid solutions prepared with these adjuvants in the respective weight ratios also proved to be stable (visual and HPLC) after storage at 40 ° C. and 75% relative humidity for four weeks.
- Excipient and rasagiline were mixed in a weight ratio of 10: 1 and 2: 1, respectively, in a petri dish or beaker.
- a 30% (by volume) aqueous ethanolic solution was added to the solid mixture, acidified with 0.1 mol / l HCl (0.5 ml to 100 ml of solvent) and taken to complete solution ( ⁇ 2 h) on a magnetic stirrer touched. Subsequently, the solution was dried in a vacuum oven at 40 0 C and 0.1 bar for 120 h.
- the products were analyzed visually, ie by light microscopy and with the naked eye (for homogeneity) and by means of HPLC (active ingredient content and impurities).
- auxiliaries were found to be independent of the weight ratio of sorbitol, PVP 30, HPMC 615, PEG 4000, PEG 20000, HPC HF and Pluronic F68.
- the with these excipients solid solutions also proved to be stable (visual and HPLC) after four weeks of storage at 40 ° C. and 75% relative humidity.
- Rasagiiine tartrate based on 10 g of the free base, together with 20 g of sorbitol, 200 ml of a 30% (volume percent) aqueous ethanol solution was added. After addition of 1 ml of 0.1 molar hydrochloric acid was stirred for 3 h on the magnetic stirrer.
- the clear solution thus obtained was in a fluidized bed granulator (Glatt GPCG 3.1, inlet temperature 70 ° C, outlet temperature 45 0 C, spray pressure 1, 6 bar, spray rate about 1, 5 g / min) to 300 g Nonpareilles with a diameter of 500 microns sprayed.
- Rasagiiine tartrate based on 5 g of the free base, together with 50 g HPMC was added 500 ml of a 20% (volume percent) aqueous ethanol solution. After addition of 1 ml of 0.1 molar hydrochloric acid was stirred for 3 h on the magnetic stirrer.
- the clear solution thus obtained was in a fluidized bed granulator (Glatt GPCG 3.1, inlet temperature 70 0 C, outlet temperature 45 0 C, spray pressure 1, 6 bar, spray rate about 1, 5 g / min) onto nonpareils having a diameter of 400 to 500 microns sprayed.
- Rasagiiintartrat based on 1 g of the free base, together with 2 g Pluronic F68 was added with 100 ml of water and stirred for 3 h on the magnetic stirrer.
- the resulting clear solution was in a fluidized bed granulator (Glatt GPCG 3.1, inlet temperature 70 0 C, outlet temperature 45 0 C, spray pressure 1, 6 bar, spray speed about 1, 5 g / min) on Nonpareilles with a diameter of 500 to 600 microns sprayed.
- An extrudate of 72.05 g of rasagiline tartrate and 500 g of PEG 4000 was prepared according to Example 2 with the following temperature settings on the extruder: cylinder 1/55 0 C, cylinder 2/60 0 C, cylinder 3/63 0 C, cylinder 4/60 0 C, Cylinder 5/55 0 C, outlet nozzle / 55 0 C, product temperature / 55 ° C.
- Mannitol, corn starch and pregelatinised cornstarch were weighed into a glass jar, mixed for 20 minutes with a Turbula T10B shaker at 23 rpm and then sieved through a sieve of 500 ⁇ m mesh size.
- Stearic acid, talc and Aerosil were sieved through a 250 ⁇ m sieve and mixed together with the other excipients for 5 minutes. After addition of the extrudate, the entire batch was mixed for a further 7 minutes. From this mixture were pressed with a hand press and a pressing force of about 4 kN to 8 kN tablets.
- Avicel and pregelatinized cornstarch were weighed into a glass jar, mixed for 20 minutes with a Turbula T10B shaker at 23 rpm and then sieved through a 500 ⁇ m mesh sieve. Mg stearate, citric acid and Aerosil were sieved through a 250 ⁇ m sieve and mixed together with the other excipients for 5 minutes. After addition of the extrudate, the entire Mix mixed for another 7 minutes. From this mixture were pressed with a hand press and a pressing force of about 4 kN to 8 kN tablets.
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Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011541468A JP2012512840A (ja) | 2008-12-19 | 2009-12-18 | ラサギリン成分を含有する固体組成物 |
AU2009329529A AU2009329529A1 (en) | 2008-12-19 | 2009-12-18 | Solid composition containing the ingredient rasagiline |
US13/140,402 US20110313050A1 (en) | 2008-12-19 | 2009-12-18 | Solid composition containing the ingredient rasagiline |
EP09795429A EP2367533A1 (de) | 2008-12-19 | 2009-12-18 | Feste zusammensetzung mit dem wirkstoff rasagilin |
CA2747311A CA2747311A1 (en) | 2008-12-19 | 2009-12-18 | Solid composition containing the ingredient rasagiline |
IL213583A IL213583A0 (en) | 2008-12-19 | 2011-06-15 | Solid compositions containing the ingredient rasagiline |
US13/967,240 US20130345310A1 (en) | 2008-12-19 | 2013-08-14 | Solid composition containing the ingredient rasagiline |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102008064061.1 | 2008-12-19 | ||
DE102008064061A DE102008064061A1 (de) | 2008-12-19 | 2008-12-19 | Feste Zusammensetzung mit dem Wirkstoff Rasagilin |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/967,240 Continuation US20130345310A1 (en) | 2008-12-19 | 2013-08-14 | Solid composition containing the ingredient rasagiline |
Publications (1)
Publication Number | Publication Date |
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WO2010070090A1 true WO2010070090A1 (de) | 2010-06-24 |
Family
ID=42154634
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2009/067508 WO2010070090A1 (de) | 2008-12-19 | 2009-12-18 | Feste zusammensetzung mit dem wirkstoff rasagilin |
Country Status (8)
Country | Link |
---|---|
US (2) | US20110313050A1 (de) |
EP (1) | EP2367533A1 (de) |
JP (1) | JP2012512840A (de) |
AU (1) | AU2009329529A1 (de) |
CA (1) | CA2747311A1 (de) |
DE (1) | DE102008064061A1 (de) |
IL (1) | IL213583A0 (de) |
WO (1) | WO2010070090A1 (de) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7968749B2 (en) | 2008-06-19 | 2011-06-28 | Teva Pharmaceutical Industries, Ltd. | Process for preparing and drying solid rasagiline base |
EP2389927A1 (de) * | 2010-05-30 | 2011-11-30 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmazeutische Formulationen von Rasagilin |
US8080584B2 (en) | 2009-01-23 | 2011-12-20 | Teva Pharmaceuticals Industries, Ltd. | Delayed release rasagiline citrate formulation |
US8188149B2 (en) | 2007-09-17 | 2012-05-29 | Teva Pharmaceutical Industries, Ltd. | Use of R(+)-N-propargy1-1-aminoindan to treat or prevent hearing loss |
EP2598136A1 (de) * | 2010-07-27 | 2013-06-05 | Teva Pharmaceutical Industries Ltd. | Dispersionen von rasagilincitrat |
DE102012000786A1 (de) * | 2012-01-18 | 2013-07-18 | Stada Arzneimittel Ag | Verfahren zur Herstellung einer festen pharmazeutischen Zusammensetzung, enthaltend den Wirkstoff Rasagilin |
US8569379B2 (en) | 2010-07-27 | 2013-10-29 | Teva Pharmaceutical Industries Ltd. | Use of rasagiline for the treatment of olfactory dysfunction |
US8809310B2 (en) | 2006-02-21 | 2014-08-19 | Teva Pharmaceutical Industries, Ltd. | Use of rasagiline for the treatment of multiple system atrophy |
US8946300B2 (en) | 2006-04-03 | 2015-02-03 | Teva Pharmaceutical Industries, Ltd. | Use of rasagilline for the treatment of restless legs syndrome |
US8946482B2 (en) | 2009-07-09 | 2015-02-03 | Ratiopharm Gmbh | Salts of rasagiline and pharmaceutical preparations thereof |
US9308182B2 (en) | 2012-08-17 | 2016-04-12 | Teva Pharmaceutical Industries, Ltd. | Parenteral formulations of rasagiline |
US9339469B2 (en) | 2011-10-10 | 2016-05-17 | Teva Pharmaceutical Industries, Ltd. | R(+)-N-methyl-propargyl-aminoindan |
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US8163960B2 (en) | 2008-06-19 | 2012-04-24 | Teva Pharmaceutical Industries, Ltd. | Process for preparing and drying solid rasagiline base |
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US8080584B2 (en) | 2009-01-23 | 2011-12-20 | Teva Pharmaceuticals Industries, Ltd. | Delayed release rasagiline citrate formulation |
JP2012515775A (ja) * | 2009-01-23 | 2012-07-12 | テバ ファーマシューティカル インダストリーズ リミティド | 遅延放出ラサギリン製剤 |
JP2015091813A (ja) * | 2009-01-23 | 2015-05-14 | テバ ファーマシューティカル インダストリーズ リミティド | 遅延放出ラサギリン製剤 |
US8946482B2 (en) | 2009-07-09 | 2015-02-03 | Ratiopharm Gmbh | Salts of rasagiline and pharmaceutical preparations thereof |
WO2012004691A3 (en) * | 2010-05-30 | 2012-04-12 | Abdi Ibrahim Ilac Sanayi Ve Ticaret Anonim Sirketi | Pharmaceutical formulations of rasagiline |
EP2389927A1 (de) * | 2010-05-30 | 2011-11-30 | Abdi Ibrahim Ilac Sanayi ve Ticaret Anonim Sirketi | Pharmazeutische Formulationen von Rasagilin |
EP2598136A1 (de) * | 2010-07-27 | 2013-06-05 | Teva Pharmaceutical Industries Ltd. | Dispersionen von rasagilincitrat |
US8691872B2 (en) | 2010-07-27 | 2014-04-08 | Teva Pharmaceutical Industries Ltd. | Dispersions of rasagiline citrate |
US8569379B2 (en) | 2010-07-27 | 2013-10-29 | Teva Pharmaceutical Industries Ltd. | Use of rasagiline for the treatment of olfactory dysfunction |
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US9339469B2 (en) | 2011-10-10 | 2016-05-17 | Teva Pharmaceutical Industries, Ltd. | R(+)-N-methyl-propargyl-aminoindan |
US9346746B2 (en) | 2011-10-10 | 2016-05-24 | Teva Pharmaceutical Industries, Ltd. | R(+)-N-formyl-propargyl-aminoindan |
DE102012000786A1 (de) * | 2012-01-18 | 2013-07-18 | Stada Arzneimittel Ag | Verfahren zur Herstellung einer festen pharmazeutischen Zusammensetzung, enthaltend den Wirkstoff Rasagilin |
US9308182B2 (en) | 2012-08-17 | 2016-04-12 | Teva Pharmaceutical Industries, Ltd. | Parenteral formulations of rasagiline |
Also Published As
Publication number | Publication date |
---|---|
DE102008064061A1 (de) | 2010-06-24 |
IL213583A0 (en) | 2011-07-31 |
US20110313050A1 (en) | 2011-12-22 |
EP2367533A1 (de) | 2011-09-28 |
US20130345310A1 (en) | 2013-12-26 |
AU2009329529A1 (en) | 2011-07-14 |
JP2012512840A (ja) | 2012-06-07 |
CA2747311A1 (en) | 2010-06-24 |
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