WO2002043723A1 - Parental applizierbare darreichungsformen enthaltend eine suspension des salzes aus tramadol und diclofenac - Google Patents
Parental applizierbare darreichungsformen enthaltend eine suspension des salzes aus tramadol und diclofenac Download PDFInfo
- Publication number
- WO2002043723A1 WO2002043723A1 PCT/EP2001/013789 EP0113789W WO0243723A1 WO 2002043723 A1 WO2002043723 A1 WO 2002043723A1 EP 0113789 W EP0113789 W EP 0113789W WO 0243723 A1 WO0243723 A1 WO 0243723A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dosage forms
- parenterally administrable
- forms according
- administrable dosage
- ethylene oxide
- Prior art date
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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the present invention relates to administration forms which can be administered parenterally and contain a suspension of the salt from the active substances tramadol and diclofenac.
- the pharmaceutical active ingredient tramadol is often used in the form of its hydrochloride - (1RS, 2RS) -2 - [(dimethylamino) methyl] -1- (3-methoxyphenyl) cyclohexanol hydrochloride - as an analgesic to combat moderate to severe pain.
- satisfactory pain control can only be achieved by parenteral administration of the painkillers, for example if the patient is not or only poorly able to take a painkiller orally due to his physical impairment.
- a disadvantage of the parenteral administration of tramadol hydrochloride is the relatively rapid metabolism of the active ingredient from the dosage forms known hitherto, so that after its administration a longer-lasting analgesic effect cannot be achieved without increasing the dosage.
- such an increase is not desirable since it also increases the risk of undesirable side effects.
- the object underlying the present invention was therefore to provide a dosage form of the active ingredient tramadol for parenteral administration, from which this active ingredient is metabolized with a delay.
- this object is achieved by providing parenterally administrable dosage forms which contain a suspension of the active ingredient salt from tramadol and diclofenac.
- a very readily water-soluble salt of tramadol is preferably reacted with a very well water-soluble salt of diclofenac.
- Tramadol hydrochloride is preferably used as the salt of tramadol, and its sodium salt is preferably used as the salt of diclofenac.
- the active substance salt obtained in this way from tramadol and diclofenac can be isolated and, if appropriate, purified by various methods known to the person skilled in the art.
- At least 95% of the suspended salt particles of the parenterally administrable dosage forms according to the invention have a particle diameter in the range of ⁇ 50 ⁇ m, preferably ⁇ 30 ⁇ m, particularly preferably ⁇ 5 ⁇ m.
- the particle diameters of the suspended salt particles are determined by means of a scattered light measurement in a Coulter ® LS 230 laser particle analyzer with HFM and MVM module (Beckman-Coulter Electronics GmbH, Krefeld, Germany).
- the suspension medium of the administration forms which can be administered parenterally according to the invention can be hydrophobic or hydrophilic.
- One embodiment of the present invention is therefore that the active ingredient salt from tramadol and diclofenac is suspended in a hydrophobic pharmaceutically acceptable suspension medium.
- This hydrophobic suspension medium can preferably be based on pharmaceutically acceptable synthetic, semisynthetic or natural oils or mixtures of at least two of these oils.
- synthetic, semi-synthetic or natural oils preferably medium-chain triglycerides with a chain length of C 8 to C 10 in the carboxylic acid part, soybean oil, sesame oil, peanut oil, olive oil, coconut oil, castor oil, sunflower oil, safflower oil or the corresponding hydrogenated oils or mixtures of at least two of the oils mentioned above can be used.
- Castor oil is particularly preferably used.
- these oils can also be equipped with physiologically compatible antioxidants, preferably tocopherols and / or their esters, butylated hydroxyanisole or butylated hydroxytoluene, preferably in amounts of 0.001 to 0.1% by weight, based on the suspension medium.
- physiologically compatible antioxidants preferably tocopherols and / or their esters, butylated hydroxyanisole or butylated hydroxytoluene, preferably in amounts of 0.001 to 0.1% by weight, based on the suspension medium.
- a physiologically compatible hydrophilic suspension medium can also be used for the dosage forms of the active ingredient salt which can be administered parenterally.
- the hydrophilic suspension medium is preferably based on water.
- the physiologically compatible hydrophilic suspension medium can contain further physiologically compatible auxiliaries.
- auxiliaries are preferably pH regulators, regulators for adjusting the osmolality, surface-active compounds, viscosity regulators, peptizers, buffers or preservatives.
- the dosage forms according to the invention can also contain one or more representatives of one or all of the other classes of excipients mentioned.
- administration forms that can be administered parenterally are physiologically compatible, surface-active
- the osmolality ie the tonicity of the dosage forms according to the invention to be administered parenterally, is preferably adjusted so that they are isotonic or at least approximately isotonic to the physiological osmolality.
- the osmolality of the dosage forms according to the invention, which can be administered parenterally, is therefore preferably set such that they are in the range from 250 to 400 mOsm / kg, particularly preferably in the range from 260 to 320 mOsm / kg and very particularly preferably in the range from 280 to 300 mOsm / kg lies.
- Preferred regulators for adjusting the osmolality are water-soluble, physiologically compatible compounds such as inorganic salts, for example alkali salts, preferably sodium chloride, sugar, for example sucrose or dextrose, sugar alcohols, for example mannitol, or polyalkylene glycols, for example polyethylene glycols, preferably with a molecular weight of 1000 to 8000 g / mol.
- inorganic salts for example alkali salts, preferably sodium chloride
- sugar for example sucrose or dextrose
- sugar alcohols for example mannitol
- polyalkylene glycols for example polyethylene glycols, preferably with a molecular weight of 1000 to 8000 g / mol.
- a mixture of at least two representatives from different regulator classes mentioned above or at least two representatives from one regulator class can also be used to adjust the osmolality.
- a regulator can also be used to adjust various properties of the dosage forms according to the invention.
- a surface active compound can also be used to adjust the osmolality.
- the pH of the dosage forms according to the invention should preferably be in the range from pH 5 to pH 8 in order to avoid further risks of cell and tissue damage.
- the dosage forms according to the invention which can be administered parenterally, can also contain physiologically compatible preservatives.
- Suitable ones are, for example, 1, 1, 1-trichloro-2-methyl-2-propanol,
- the suspension medium of the dosage forms according to the invention is water, which is used as a further auxiliary
- osmolality regulator selected from the group monosaccharides, oligosaccharides and
- Sugar alcohols preferably sucrose and / or mannitol, or
- Osmolality regulators in amounts of 0.5 to 5% by weight and made of polyethylene glycols, preferably polyethylene glycols with a
- each based on the entire suspension medium including components a) and b1) or a) and b2).
- the volume of the dosage forms according to the invention that can be administered parenterally is preferably ⁇ 5 ml, particularly preferably ⁇ 4 ml and very particularly preferably ⁇ 2 ml.
- the administration forms which can be administered parenterally are preferably suitable for intramuscular or subcutaneous administration.
- the amount of the active ingredient salt to be administered to the patient in the dosage forms according to the invention can vary, for example, depending on the weight of the patient, the type or the intensity of the pain. Because of the effect of the analgesics, the person skilled in the art knows in which doses the active ingredient salt is to be used so that the desired effect is achieved.
- dosage forms according to the invention which can be administered parenterally can be prepared by customary methods known to the person skilled in the art.
- the dosage forms according to the invention are preferably produced on an aqueous basis by the method described below.
- the auxiliaries used are dissolved at room temperature or, if appropriate, with heating in water for injection purposes. If liquid auxiliaries are involved, they are mixed with water. The solution or mixture thus obtained is then sterile filtered using a filter which retains microorganisms. The pore size of this filter is usually 0.2 ⁇ m. The filtration can optionally also take place before the addition of the auxiliaries, but the further preparation of the dosage forms should then take place under aseptic conditions.
- the sterile active ingredient salt of tramadol and diclofenac is then suspended under aseptic conditions by stirring, preferably homogeneously, in the hydrophilic suspension medium thus obtained and the suspension thus obtained is then filled into suitable containers, preferably into injection bottles (vials).
- the dosage forms according to the invention on a hydrophobic basis are preferably prepared by first sterilizing the hydrophobic suspension medium by heat and optionally adding further auxiliaries.
- the sterile active ingredient salt of tramadol and diclofenac is then suspended under aseptic conditions by stirring, preferably homogeneously, in the hydrophobic suspension medium thus obtained, and the suspension thus obtained is then filled into suitable containers, preferably into injection bottles (vials).
- final sterilization can optionally be carried out by customary methods known to the person skilled in the art, for example by autoclaving.
- the suspensions according to the invention which can be administered parenterally are preferably already produced under aseptic conditions.
- the dosage forms according to the invention which can be administered parenterally are also distinguished, inter alia, by the fact that they are stable in storage over a longer period, i.e. remain applicable.
- the dosage forms according to the invention also occur for months
- Active ingredients are not an effective pain control without that the tramadol, for example, must be administered to the patient more than twice a day. This results in effective pain therapy for the patient under less stress. Furthermore, the delayed metabolism enables the setting of constant serum levels of the active ingredient tramadol in the blood serum. Height
- Active ingredient concentrations as they often occur in conventional dosage forms with rapid release of active ingredient, and the associated side effects that may be associated with them can thus be completely avoided or at least significantly reduced.
- FIG. 1 shows the concentration course of the (+) - tramadol enantiomer for the dosage forms according to the invention and for a corresponding tramadol hydrochloride dosage form in the blood serum of dogs after parenteral administration.
- FIG. 2 shows the concentration-time profiles of the (-) - tramadol enantiomer for the dosage forms according to the invention and for a corresponding tramadol hydrochloride dosage form in the blood serum of dogs after parenteral administration.
- a treatment-free time of at least 14 days was observed between each application of the dosage forms according to the invention or between each tramadol hydrochloride dosage form. After collection, the blood samples were centrifuged, the solid residue was discarded and the blood serum thus obtained was stored at a temperature below -20 ° C. until analysis.
- Each series of measurements consisted of eight calibration samples of different concentrations, quality control samples with two samples each at three different concentration levels and the samples to be analyzed of unknown concentration.
- the corresponding calibration and quality control samples were prepared in serum and processed together with the blood serum samples of unknown content.
- the amounts of the tramadol enantiomers and possibly the metabolites contained in the blood serum at the time of measurement were concentrated using diazoethane as derivatization reagent and the samples thus obtained were subsequently analyzed by means of stereoselective gas chromatography with nitrogen-selective detection.
- the osmolality of the dosage forms according to the invention was determined by lowering the freezing point according to Pharm. Eur. 97 in accordance with Chapter 2.2.35.
- the corresponding literature description is hereby introduced as a reference and is therefore considered part of the disclosure.
- the measurement was carried out using a type M measuring device (Dr. H. Knauer KG, Berlin, Germany).
- the calibration was carried out with distilled water for 0 mOsmol / kg and with a calibration solution (Dr. H. Knauer KG, Berlin, Germany) or alternatively 12.687 g sodium chloride, dissolved in 1 kg of distilled water for 400 mOsmol / kg.
- the osmolality of the solution thus obtained was determined by the method given above and was 300 mOsm / kg. 3rd stage: preparation of the dosage form
- the active ingredient salt obtained in the 1st stage was ground under aseptic conditions so that 98% of the salt particles had a particle diameter of ⁇ 30 ⁇ m. Subsequently, 293.5 mg of the salt were each suspended in 5 ml of the suspension medium obtained in the 2nd stage and filled into an injection bottle. For the necessary resuspension, 3 to 5 sterilized glass beads were also added in each case and the injection bottles were each sealed and crimped with a sterilized bromobutyl rubber stopper.
- the dosage form thus obtained was examined according to the method given above and the respective concentrations of (+) - tramadol and (-) - tramadol in the blood serum were determined.
- the result of these tests for (+) - tramadol and the values for the corresponding tramadol hydrochloride dosage form are shown in FIG. 1.
- the result for (-) - tramadol and the corresponding values for the tramadol hydrochloride dosage form are shown in FIG. 2.
- castor oil was filtered through a filter with a pore size of 5 ⁇ m (Millipore SVLP). The filtered oil was then sterilized in a sealed vessel at 150 ° C. for one hour. 2nd stage:
- the active ingredient salt prepared according to Example 1, 1st stage was ground under aseptic conditions so that 98% of the salt particles had a particle diameter of ⁇ 30 ⁇ m. Subsequently, 293.5 mg of the salt were suspended in 5 ml of the hydrophobic suspension medium obtained in step 1 and filled into an injection bottle. For any necessary
- the dosage form thus obtained was examined according to the method given above and the respective concentrations of (+) - tramadol and (-) - tramadol in the blood serum were determined.
- the result of these tests for (+) - tramadol and the values for the corresponding tramadol hydrochloride dosage form are shown in FIG. 1.
- the result for (-) - tramadol and the corresponding values for the tramadol hydrochloride dosage form are shown in FIG. 2.
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01994735A EP1368016B1 (de) | 2000-11-28 | 2001-11-27 | Parental applizierbare darreichungsformen enthaltend eine suspension des salzes aus tramadol und diclofenac |
SI200130559T SI1368016T1 (sl) | 2000-11-28 | 2001-11-27 | Dajalne oblike, ki se jih da dajati parenteralno,ki vsebujejo suspenzijo soli iz tramadola in diklofenaka |
AU2002224896A AU2002224896A1 (en) | 2000-11-28 | 2001-11-27 | Parenteral dosage forms comprising a suspension of tramadol salt and diclofenac salt |
JP2002545694A JP4188084B2 (ja) | 2000-11-28 | 2001-11-27 | トラマドールとジクロフェナクの塩の懸濁液を含有する非経口投与可能な剤形 |
DE50109572T DE50109572D1 (de) | 2000-11-28 | 2001-11-27 | Parental applizierbare darreichungsformen enthaltend eine suspension des salzes aus tramadol und diclofenac |
US10/442,701 US6875447B2 (en) | 2000-11-28 | 2003-05-21 | Parenteral dosage forms comprising a suspension of tramadol salt and diclofenac salt |
HK04103826A HK1060971A1 (en) | 2000-11-28 | 2004-05-28 | Parenteral dosage forms comprising a suspension oftramadol salt and diclofenac salt |
CY20061100859T CY1105625T1 (el) | 2000-11-28 | 2006-06-26 | Παρεντερικα χορηγησιμες μορφες χορηγησης που περιεχουν ενα αιωρημα του αλατος απο τραμαδολη και diclofenac |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10059020.9 | 2000-11-28 | ||
DE10059020A DE10059020A1 (de) | 2000-11-28 | 2000-11-28 | Parenteral applizierbare Darreichungsformen |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/442,701 Continuation US6875447B2 (en) | 2000-11-28 | 2003-05-21 | Parenteral dosage forms comprising a suspension of tramadol salt and diclofenac salt |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002043723A1 true WO2002043723A1 (de) | 2002-06-06 |
Family
ID=7664956
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2001/013789 WO2002043723A1 (de) | 2000-11-28 | 2001-11-27 | Parental applizierbare darreichungsformen enthaltend eine suspension des salzes aus tramadol und diclofenac |
Country Status (13)
Country | Link |
---|---|
US (1) | US6875447B2 (de) |
EP (1) | EP1368016B1 (de) |
JP (1) | JP4188084B2 (de) |
CN (1) | CN100384410C (de) |
AT (1) | ATE323477T1 (de) |
AU (1) | AU2002224896A1 (de) |
CY (1) | CY1105625T1 (de) |
DE (2) | DE10059020A1 (de) |
DK (1) | DK1368016T3 (de) |
ES (1) | ES2262703T3 (de) |
HK (1) | HK1060971A1 (de) |
PT (1) | PT1368016E (de) |
WO (1) | WO2002043723A1 (de) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2061599A4 (de) * | 2005-08-24 | 2014-01-22 | Telechemistry Oy | Verfahren zum prüfen einer flüssigkeitsprobe, testeinheit und automatisiertes system aus mehreren testeinheiten |
US20100029704A1 (en) * | 2007-01-29 | 2010-02-04 | Medrx Co., Ltd. | Salt of nonsteroidal anti-inflammatory drug and organic amine compound and use thereof |
AU2013204763B2 (en) * | 2008-01-14 | 2015-06-04 | Biokit, S.A. | Device for distributing particles in a fluid and methods therefor |
JP5307835B2 (ja) * | 2008-01-14 | 2013-10-02 | バイオキット,エス.アー. | 流体中に粒子を分散させる装置およびその方法 |
EP2281558A1 (de) * | 2009-08-06 | 2011-02-09 | Laboratorios Del. Dr. Esteve, S.A. | Pharmazeutische Verbindungen von O-Desmethyltramadol und COX-Inhibitoren |
EP2593096A4 (de) * | 2010-07-12 | 2014-02-26 | Yung Shin Pharm Ind Co Ltd | Diclofenac-salz von tramadol |
CA2833307C (en) | 2011-04-12 | 2018-01-23 | Revogenex Inc. | Intravenous administration of tramadol |
US9980900B2 (en) | 2015-12-22 | 2018-05-29 | Revogenex Ireland Ltd | Intravenous administration of tramadol |
US9693949B1 (en) | 2015-12-22 | 2017-07-04 | Revogenex Ireland Ltd | Intravenous administration of tramadol |
US10022321B2 (en) | 2016-06-30 | 2018-07-17 | Revogenex Ireland Ltd. | Intravenous administration of tramadol |
Citations (5)
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US4016273A (en) * | 1975-07-16 | 1977-04-05 | American Cyanamid Company | Sustained release forms of certain oxazepines for parenteral administration |
US5283067A (en) * | 1987-01-30 | 1994-02-01 | Ciba-Geigy Corporation | Parenteral suspensions |
US5336691A (en) * | 1991-09-06 | 1994-08-09 | Mcneilab, Inc. | Composition comprising a tramadol material and acetaminophen and its use |
US5958379A (en) * | 1994-09-30 | 1999-09-28 | Mika Pharma Gesellschaft Fuer Die Entwicklung Und Vermarktung Pharmazeutischer Producte Mbh | Pharmaceutical composition |
WO2000072827A2 (en) * | 1999-05-27 | 2000-12-07 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
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DE3324193A1 (de) * | 1983-07-05 | 1985-01-17 | Troponwerke Gmbh & Co Kg | Depot-antiphlogistika |
AU661723B2 (en) * | 1991-10-30 | 1995-08-03 | Mcneilab, Inc. | Composition comprising a tramadol material and a non-steroidal anti-inflammatory drug |
CA2143044C (en) * | 1994-02-21 | 2005-04-12 | Yasutaka Igari | Matrix for sustained-release preparation |
AU7472798A (en) * | 1997-05-07 | 1998-11-27 | Algos Pharmaceutical Corporation | Cox-2 inhibitors in combination with nmda-blockers for treating pain |
DE19732928C2 (de) * | 1997-07-31 | 2000-05-18 | Gruenenthal Gmbh | Verwendung substituierter Imidazolidin-2,4-dion-Verbindungen als Schmerzmittel |
EP1146905A1 (de) * | 1998-11-12 | 2001-10-24 | Algos Pharmaceutical Corporation | Cox-2 hemmstoffe in kombination mit nmda-blockern zur behandlung von schmerzen |
WO2000029022A1 (en) * | 1998-11-12 | 2000-05-25 | Algos Pharmaceutical Corporation | Cox-2 inhibitors in combination with centrally acting analgesics |
-
2000
- 2000-11-28 DE DE10059020A patent/DE10059020A1/de not_active Withdrawn
-
2001
- 2001-11-27 DE DE50109572T patent/DE50109572D1/de not_active Expired - Lifetime
- 2001-11-27 AU AU2002224896A patent/AU2002224896A1/en not_active Abandoned
- 2001-11-27 AT AT01994735T patent/ATE323477T1/de active
- 2001-11-27 PT PT01994735T patent/PT1368016E/pt unknown
- 2001-11-27 CN CNB018196829A patent/CN100384410C/zh not_active Expired - Fee Related
- 2001-11-27 EP EP01994735A patent/EP1368016B1/de not_active Expired - Lifetime
- 2001-11-27 JP JP2002545694A patent/JP4188084B2/ja not_active Expired - Fee Related
- 2001-11-27 ES ES01994735T patent/ES2262703T3/es not_active Expired - Lifetime
- 2001-11-27 DK DK01994735T patent/DK1368016T3/da active
- 2001-11-27 WO PCT/EP2001/013789 patent/WO2002043723A1/de active IP Right Grant
-
2003
- 2003-05-21 US US10/442,701 patent/US6875447B2/en not_active Expired - Fee Related
-
2004
- 2004-05-28 HK HK04103826A patent/HK1060971A1/xx not_active IP Right Cessation
-
2006
- 2006-06-26 CY CY20061100859T patent/CY1105625T1/el unknown
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US4016273A (en) * | 1975-07-16 | 1977-04-05 | American Cyanamid Company | Sustained release forms of certain oxazepines for parenteral administration |
US5283067A (en) * | 1987-01-30 | 1994-02-01 | Ciba-Geigy Corporation | Parenteral suspensions |
US5336691A (en) * | 1991-09-06 | 1994-08-09 | Mcneilab, Inc. | Composition comprising a tramadol material and acetaminophen and its use |
US5958379A (en) * | 1994-09-30 | 1999-09-28 | Mika Pharma Gesellschaft Fuer Die Entwicklung Und Vermarktung Pharmazeutischer Producte Mbh | Pharmaceutical composition |
WO2000072827A2 (en) * | 1999-05-27 | 2000-12-07 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
Non-Patent Citations (1)
Title |
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GRONING R: "Computer-controlled drug release from small-sized dosage forms", JOURNAL OF CONTROLLED RELEASE, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 48, no. 2-3, 13 October 1997 (1997-10-13), pages 185 - 193, XP004125855, ISSN: 0168-3659 * |
Also Published As
Publication number | Publication date |
---|---|
EP1368016B1 (de) | 2006-04-19 |
CN100384410C (zh) | 2008-04-30 |
HK1060971A1 (en) | 2004-09-03 |
DE50109572D1 (de) | 2006-05-24 |
JP4188084B2 (ja) | 2008-11-26 |
DE10059020A1 (de) | 2002-05-29 |
CY1105625T1 (el) | 2010-12-22 |
AU2002224896A1 (en) | 2002-06-11 |
US20030203037A1 (en) | 2003-10-30 |
ATE323477T1 (de) | 2006-05-15 |
US6875447B2 (en) | 2005-04-05 |
CN1477955A (zh) | 2004-02-25 |
PT1368016E (pt) | 2006-08-31 |
DK1368016T3 (da) | 2006-07-31 |
EP1368016A1 (de) | 2003-12-10 |
ES2262703T3 (es) | 2006-12-01 |
JP2004514692A (ja) | 2004-05-20 |
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