WO2002072080A2 - Solutions de paracetamol stables au stockage et pretes a la perfusion - Google Patents

Solutions de paracetamol stables au stockage et pretes a la perfusion Download PDF

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Publication number
WO2002072080A2
WO2002072080A2 PCT/EP2002/002696 EP0202696W WO02072080A2 WO 2002072080 A2 WO2002072080 A2 WO 2002072080A2 EP 0202696 W EP0202696 W EP 0202696W WO 02072080 A2 WO02072080 A2 WO 02072080A2
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WO
WIPO (PCT)
Prior art keywords
paracetamol
solution according
solution
per liter
cysteine
Prior art date
Application number
PCT/EP2002/002696
Other languages
German (de)
English (en)
Other versions
WO2002072080A3 (fr
Inventor
Bernd Eschenbach
Hans-Jörg Müller
Klaus Sommermeyer
Original Assignee
Fresenius Kabi De Gmbh
Bernd Eschenbach
Mueller Hans-Joerg
Klaus Sommermeyer
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 Fresenius Kabi De Gmbh, Bernd Eschenbach, Mueller Hans-Joerg, Klaus Sommermeyer filed Critical Fresenius Kabi De Gmbh
Priority to EP02724223A priority Critical patent/EP1372628A2/fr
Priority to AU2002254942A priority patent/AU2002254942A1/en
Publication of WO2002072080A2 publication Critical patent/WO2002072080A2/fr
Publication of WO2002072080A3 publication Critical patent/WO2002072080A3/fr

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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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • 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
    • A61K9/08—Solutions

Definitions

  • the present invention relates to paracetamol solutions that can be used medically.
  • the invention relates to a storage-stable, particle- and discoloration-free, parenterally administrable, in particular infusible, aqueous .
  • Paracetamol solution process for the preparation of such a solution and containers containing such solutions.
  • Paracetamol is a standard analgesic that has been established for decades and, due to its favorable pharmacological properties (analgesic and antipyretic effect with very little antiphlogistic effect), is routinely used for postoperative pain therapy in childhood, for example.
  • the application is mostly prophylactic when introducing anesthesia or during the surgical intervention, usually rectally.
  • paracetamol is only commercially available as a sterile powder in the form of an ester prodrug (pro-dafalgam, active ingredient propacetamol, chemically the diethylaminoglycine ester of paracetamol).
  • This dosage form must first be reconstituted and then with an infusion carrier solution, e.g. Glucose 5% or isotonic saline, further diluted to a suitable ready-to-use infusion solution.
  • an infusion carrier solution e.g. Glucose 5% or isotonic saline
  • a solubility of the active substance to the extent specified in EP 0 916 347 AI is not essential.
  • pro-dafalgam is further diluted with 100 ml isotonic saline solution or 5% glucose solution to form the ready-to-use infusion solution.
  • the water solubility of paracetamol would in itself be sufficient for such a preparation.
  • due to stability problems no ready-made paracetamol infusions are on the market.
  • aqueous solutions of paracetamol tend to develop discoloration even after short storage times.
  • turbidity occurs and particles or precipitates are formed.
  • aged infusion solutions of paracetamol can of course no longer be used.
  • the task was therefore to develop a stable, physiologically acceptable and inexpensive to manufacture paracetamol pre-infusion solution.
  • a storage-stable, particle- and discoloration-free, parenterally administrable, in particular infusible, aqueous solution of the paracetamol according to the invention has in mixture a) 1 to 17 grams per liter of paracetamol and b) 0.01 to 0.17 grams per liter of one or more physiologically compatible antioxidants on which are selected from the group consisting of ascorbic acid, N-acetyl-L-cysteine and SH group-containing stabilizer compounds other than N-acetyl-L-cysteine, the aqueous solution being free of organic solvents, has a pH in the range of 5.5 to 6.5 and an oxygen content of less than 0.50 milligrams per liter.
  • An essential component of the solution according to the invention is paracetamol.
  • the amount of paracetamol contained in the solution according to the invention can vary over a certain range. Depending on the intended use, the aim is to achieve the highest possible concentration of paracetamol in the solution.
  • the solubility of the paracetamol in water at room temperature is about 17 grams per liter. However, depending on the other ingredients contained in the solution, the solubility can also be higher than 17 grams per liter.
  • the solution according to the invention has 5 to 15, preferably 7.5 to 12.5, grams per liter of paracetamol.
  • a particularly user-friendly solution that is ideally suited for most standard cases has a paracetamol active ingredient content of 10 grams per liter.
  • the solution for infusion according to the invention contains as a further essential component a physiologically compatible antioxidant.
  • a physiologically compatible antioxidant are compounds selected from the group consisting of ascorbic acid, N-acetyl-L-cysteine and SH group-containing stabilizers. Compounds other than N-acetyl-L-cysteine exist. The latter group includes z. B. Cysteine.
  • N-Acetyl-L-cysteine is particularly preferred among the compounds having an antioxidative effect for the invention.
  • a single connection can be used as a stabilizer. Mixtures of two or more of the stabilizing compounds can also be used.
  • the concentration of the stabilizing compounds in the infusion solution is in the range between 0.01 and 0.17 grams per liter.
  • the solution of the invention has 0.05 to 0.15, preferably 0.075 to 0.125 grams per liter of stabilizing compound, particularly preferably N-acetyl-L-cysteine.
  • the ratio of paracetamol a) to stabilizing compound b) is advantageously in the range from 10: 1 to 1000: 1, based on the weight of the compounds.
  • a weight ratio of a) to b) in the range from about 50: 1 to 500: 1, expediently 80: 1 to 200: 1 is particularly preferred.
  • Very good stability data are achieved when the weight ratio a): b) is about 100: 1 is.
  • the solution according to the invention is free from organic solvents.
  • the solutions of the invention have a defined pH, which is in a range between 5.5 and 6.5. This helps to stabilize the solution as well as to ensure the physiological tolerance of the solution. Solutions which have a pH in the range between 5.75 and 6.25, preferably between 5.9 and 6.1, are particularly useful. Surprisingly, the optimum pH of the solution for the best stability is about 6.0 to 6.1, while EP-A 0 916 347 discloses an optimum of about 5.5.
  • the stability of the solution according to the invention is increased by reducing the free oxygen content in the solution.
  • the oxygen content of the solution is less than 0.50 milligrams per liter.
  • the oxygen content of the solution is preferably as low as possible.
  • the setting of the preferred pH range for the solution according to the invention can be facilitated, for example, with a buffer system. It is preferred that the solution has an amount of a physiologically compatible buffer system that is sufficient to set the pH value to a desired value.
  • a physiologically compatible buffer system that is sufficient to set the pH value to a desired value.
  • the substances familiar to the person skilled in the art are suitable for this. This is a particularly preferred embodiment characterized in that it has glycerol-1 (2) dihydrogen phosphate as the pH buffer.
  • the solution of the invention can have further additives. So it can make sense to isotonize the solution.
  • Special solutions of the invention are therefore characterized in that they have one or more isotonizing agents, preferably NaCl or glycerol.
  • the use of NaCl is particularly expedient from a physiological point of view, while the use of glycerol can improve the solubility of the paracetamol.
  • the solution for infusion can contain other pharmaceutical active ingredients in addition to paracetamol.
  • Solutions that contain one or more other active pharmaceutical ingredients from the group of local anesthetics, analgesics and antispasmodics in combination with paracetamol are particularly interesting.
  • the co-administration of paracetamol and lidocaine is preferred for some applications.
  • a formulation can preferably additionally contain codeine phosphate.
  • an infusion solution according to the invention containing paracetamol, lidocaine and hyoscin-N-butyl bromide.
  • the invention also relates to a method for producing a solution as described and defined herein, in which
  • A) presents water for injections with an oxygen content of less than 0.50 mg / 1;
  • the solution adjusted to the desired pH is filtered through a 0.2 ⁇ m membrane filter and then filled into containers for infusion solutions and heat-sterilized at 121 ° C. for 15 minutes.
  • a further preferred variant of the process for the preparation of the solution according to the invention provides that an inert gas is passed through the water in step A) in order to expel the oxygen, and that the process is carried out under an inert gas atmosphere when vemixing in step B) and, if appropriate, in all further steps ,
  • an inert gas is passed through the water in step A) in order to expel the oxygen
  • the process is carried out under an inert gas atmosphere when vemixing in step B) and, if appropriate, in all further steps .
  • nitrogen or argon are suitable as inert gases or protective gases.
  • the invention also includes containers having a solution defined therein.
  • the containers can be bottles or bags, as are customary for ready-to-use solutions.
  • Containers made of glass or plastic are preferred. If the containers are plastic, they preferably consist of a material based on polyolefins and may be surrounded by a second bag which contains an oxygen base layer, possibly with an oxygen absorber between the bags.
  • a defined amount of water (984 ml) is placed at room temperature for injection purposes. Nitrogen can be passed through the template so as to reduce the oxygen content of the water.
  • a necessary correction of the pH to the range from 5.7 to 6.3 is carried out by adding a small amount of 0 to 0.44 ml per liter of 25% hydrochloric acid.
  • the solution is filled into a glass or plastic container under an inert gas atmosphere and sealed airtight.
  • the closed containers are sterilized at 121 ° C for 15 min.
  • the sterilized and cooled containers are stored for 2 or 3 months at 4-8 ° C in the refrigerator, at 25 ° C or at 40 ° C in the warming cabinet.
  • the batch showed discoloration, sediment and a strong pH shift due to the hydrolysis.
  • a batch was prepared as in Comparative Example 1 with a pH adjustment to pH 6.2.
  • the acetate content of the solution can be regarded as a measure of the hydrolysis of the active ingredient paracetamol during and after storage. It is determined enzymatically. At the start of storage, the acetate content is approximately 0.2 mg / 1. The lower the content determined according to the storage status, the less the paracetamol is hydrolyzed.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des solutions aqueuses de paracétamol stables au stockage, exemptes de particules et de décoloration, administrables par voie parentérale, en particulier par perfusion, caractérisées en ce qu'elles contiennent, en mélange, a) 1 à 17 grammes par litre de paracétamol et b) 0,01 à 0,17 gramme par litre d'un ou plusieurs antioxydants physiologiquement compatibles, choisis dans le groupe comprenant l'acide ascorbique, la N-acétyl-L-cystéine et des composés stabilisants renfermant des groupes SH qui sont différents de la N-acétyl-L-cystéine, en ce que la solution aqueuse est exempte de solvants organiques et présente un pH compris entre 5,5 et 6,5 et une teneur en oxygène inférieure à 0,50 milligramme par litre. L'invention concerne en outre un procédé d'obtention de telles solutions, ainsi que des récipients en verre ou en matière plastique renfermant lesdites solutions.
PCT/EP2002/002696 2001-03-13 2002-03-12 Solutions de paracetamol stables au stockage et pretes a la perfusion WO2002072080A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP02724223A EP1372628A2 (fr) 2001-03-13 2002-03-12 Solutions de paracetamol stables au stockage et pretes a la perfusion
AU2002254942A AU2002254942A1 (en) 2001-03-13 2002-03-12 Paracetamol solutions which are stable in storage and ready for infusion

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10112325.6 2001-03-13
DE10112325A DE10112325A1 (de) 2001-03-13 2001-03-13 Lagerstabile Fertiginfusionslösungen des Paracetamols

Publications (2)

Publication Number Publication Date
WO2002072080A2 true WO2002072080A2 (fr) 2002-09-19
WO2002072080A3 WO2002072080A3 (fr) 2002-11-28

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PCT/EP2002/002696 WO2002072080A2 (fr) 2001-03-13 2002-03-12 Solutions de paracetamol stables au stockage et pretes a la perfusion

Country Status (4)

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EP (1) EP1372628A2 (fr)
AU (1) AU2002254942A1 (fr)
DE (1) DE10112325A1 (fr)
WO (1) WO2002072080A2 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006517544A (ja) * 2003-02-14 2006-07-27 スアン，トー グエン 注射用パラセタモール液状製剤
EP1752139A1 (fr) 2005-08-05 2007-02-14 TheraSelect GmbH Formulation stable et liquide de la paracétamol
EP1889607A1 (fr) * 2006-07-18 2008-02-20 Genfarma Laboratorio S.L. Formule du paracetamol liquide injectable
WO2008135601A2 (fr) * 2007-05-08 2008-11-13 Docpharma Nv/Sa Formulation stable pour le stockage de médicaments phénoliques sensibles à l'oxydation, en particulier le paracétamol, comprenant une solution aqueuse du médicament désoxygénée par un procédé de fabrication de la formulation à température contrôlée
EP2243477A1 (fr) 2009-04-22 2010-10-27 Fresenius Kabi Deutschland GmbH Paracétamol destiné à l'administration parentérale
US20110015273A1 (en) * 2008-01-17 2011-01-20 Rajnarayana Kandhagatla Stable pharmaceutical aqueous compositions
WO2011018522A1 (fr) 2009-08-13 2011-02-17 Neogen N.V. Formulation de paracétamol en solution aqueuse stable en stockage
WO2011071400A1 (fr) * 2009-12-10 2011-06-16 Tecnimede - Sociedade Técnico-Medicinal, S.A. Procédé et composition pour préparation de formulations liquides stables de paracétamol
EP2377516A1 (fr) * 2010-04-14 2011-10-19 B. Braun Melsungen AG Composition de paracétamol
US8178121B2 (en) 2001-10-16 2012-05-15 Baxter International Inc. Ready-to-use paracetamol injection solutions containing propylene glycol as the only cosolvent
WO2012107093A1 (fr) 2011-02-10 2012-08-16 Neogen N.V. Formulation de paracétamol en solution aqueuse stable au stockage
WO2013108180A1 (fr) 2012-01-16 2013-07-25 Novocat Farma, S. A. Composition aqueuse de paracétamol pour injection
CN104487051A (zh) * 2012-06-29 2015-04-01 辛苔蒂加股份有限公司 用于脊椎施用的可注射过饱和对乙酰氨基酚溶液
EP1379232B1 (fr) 2001-03-30 2015-07-29 The Board of Trustees of The Leland Stanford Junior University Compositions de n-acetylcysteine et methodes de traitement et de prevention de la toxicite des medicaments
EP2464332B1 (fr) 2009-08-13 2016-03-02 Neogen N.V. Formulation de paracétamol en solution aqueuse stable en stockage
WO2016156147A1 (fr) 2015-03-27 2016-10-06 Grünenthal GmbH Formulation stable pour l'administration parentérale de tapentadol
EA028075B1 (ru) * 2014-04-29 2017-10-31 Мыкола Ивановыч ГУМЕНЮК Фармацевтическая композиция
WO2018055070A1 (fr) 2016-09-23 2018-03-29 Grünenthal GmbH Formulation stable pour l'administration parentérale de tapentadol
US11547678B2 (en) 2011-03-04 2023-01-10 Gruenenthal Gmbh Aqueous pharmaceutical formulation of tapentadol for oral administration

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112782332A (zh) * 2021-02-04 2021-05-11 深圳市药品检验研究院（深圳市医疗器械检测中心） 一种对乙酰氨基酚药品中对氨基酚杂质的hplc检测方法

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EP0916347A1 (fr) * 1997-11-18 1999-05-19 Uni-Pharma Kleon Tsetis A.B.E.E., Farmakeftika Ergastiria Solutions pharmaceutiques injectables contenant du paracétamol et des associations du paracétamol avec d'autres substances actives
US6028222A (en) * 1996-08-05 2000-02-22 Scr Pharmatop Stable liquid paracetamol compositions, and method for preparing same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6028222A (en) * 1996-08-05 2000-02-22 Scr Pharmatop Stable liquid paracetamol compositions, and method for preparing same
EP0916347A1 (fr) * 1997-11-18 1999-05-19 Uni-Pharma Kleon Tsetis A.B.E.E., Farmakeftika Ergastiria Solutions pharmaceutiques injectables contenant du paracétamol et des associations du paracétamol avec d'autres substances actives

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1379232B1 (fr) 2001-03-30 2015-07-29 The Board of Trustees of The Leland Stanford Junior University Compositions de n-acetylcysteine et methodes de traitement et de prevention de la toxicite des medicaments
US8178121B2 (en) 2001-10-16 2012-05-15 Baxter International Inc. Ready-to-use paracetamol injection solutions containing propylene glycol as the only cosolvent
JP2006517544A (ja) * 2003-02-14 2006-07-27 スアン，トー グエン 注射用パラセタモール液状製剤
JP4861162B2 (ja) * 2003-02-14 2012-01-25 スアン，トー グエン 注射用パラセタモール液状製剤
EP1592414B1 (fr) * 2003-02-14 2010-04-21 Tho Nguyen-Xuan Formulation liquide injectable de paracetamol
US8071619B2 (en) 2003-02-14 2011-12-06 Tho Nguyen-Xuan Injectable liquid formulation of paracetamol
EP1752139A1 (fr) 2005-08-05 2007-02-14 TheraSelect GmbH Formulation stable et liquide de la paracétamol
DE102005037653A1 (de) * 2005-08-05 2007-02-15 Theraselect Gmbh Stabile, flüssige Formulierung von Paracetamol
US9943479B2 (en) 2006-07-18 2018-04-17 Genfarma Laboratorio S.L. Injectable liquid paracetamol formulation
EP1889607A1 (fr) * 2006-07-18 2008-02-20 Genfarma Laboratorio S.L. Formule du paracetamol liquide injectable
US9943492B2 (en) 2006-07-18 2018-04-17 Genfarma Laboratorio S.L. Injectable liquid paracetamol formulation
WO2008135601A2 (fr) * 2007-05-08 2008-11-13 Docpharma Nv/Sa Formulation stable pour le stockage de médicaments phénoliques sensibles à l'oxydation, en particulier le paracétamol, comprenant une solution aqueuse du médicament désoxygénée par un procédé de fabrication de la formulation à température contrôlée
WO2008135601A3 (fr) * 2007-05-08 2009-06-18 Docpharma Nv Sa Formulation stable pour le stockage de médicaments phénoliques sensibles à l'oxydation, en particulier le paracétamol, comprenant une solution aqueuse du médicament désoxygénée par un procédé de fabrication de la formulation à température contrôlée
EP1992334A1 (fr) * 2007-05-08 2008-11-19 Docpharma NV/SA Formule stable pour le stockage de médicament phénolique sensible à l'oxydation, spécialement le paracétamol, et qui comprend une solution de médicament aqueuse désoxygénée par le processus de fabrication à température contrôlée de la formule
US20110015273A1 (en) * 2008-01-17 2011-01-20 Rajnarayana Kandhagatla Stable pharmaceutical aqueous compositions
US8741959B2 (en) 2009-04-22 2014-06-03 Fresenius Kabi Deutschland Gmbh Paracetamol for parenteral administration
EP2243477A1 (fr) 2009-04-22 2010-10-27 Fresenius Kabi Deutschland GmbH Paracétamol destiné à l'administration parentérale
EP2626068A1 (fr) 2009-04-22 2013-08-14 Fresenius Kabi Deutschland GmbH Paracétamol destiné à l'administration parentérale
US8404891B2 (en) 2009-08-13 2013-03-26 Neogen N.V. Storage-stable formulation of paracetamol in aqueous solution
US8404748B2 (en) 2009-08-13 2013-03-26 Neogen N.V. Storage-stable formulation of paracetamol in aqueous solution
WO2011018522A1 (fr) 2009-08-13 2011-02-17 Neogen N.V. Formulation de paracétamol en solution aqueuse stable en stockage
EP2464332B1 (fr) 2009-08-13 2016-03-02 Neogen N.V. Formulation de paracétamol en solution aqueuse stable en stockage
US20120245230A1 (en) * 2009-12-10 2012-09-27 Tecnimede-Sociedade Tecnico- Medicinal, S.A. Method and composition for preparing stable liquid formulations of paracetamol
WO2011071400A1 (fr) * 2009-12-10 2011-06-16 Tecnimede - Sociedade Técnico-Medicinal, S.A. Procédé et composition pour préparation de formulations liquides stables de paracétamol
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JP2013523864A (ja) * 2010-04-14 2013-06-17 ビー．ブラウン メルズンゲン アーゲー アセトアミノフェン組成物
CN102834090A (zh) * 2010-04-14 2012-12-19 贝朗医疗有限公司 对乙酰氨基酚组合物
WO2011128364A1 (fr) * 2010-04-14 2011-10-20 B. Braun Melsungen Ag Composition d'acétaminophène
AU2011240046B2 (en) * 2010-04-14 2015-04-09 B. Braun Melsungen Ag Acetaminophen composition
WO2012107093A1 (fr) 2011-02-10 2012-08-16 Neogen N.V. Formulation de paracétamol en solution aqueuse stable au stockage
US11547678B2 (en) 2011-03-04 2023-01-10 Gruenenthal Gmbh Aqueous pharmaceutical formulation of tapentadol for oral administration
WO2013108180A1 (fr) 2012-01-16 2013-07-25 Novocat Farma, S. A. Composition aqueuse de paracétamol pour injection
US20150148379A1 (en) * 2012-06-29 2015-05-28 Sintetica S.A. Injectable Supersaturated Acetaminophen Solution for Spinal Administration
CN104487051B (zh) * 2012-06-29 2017-12-12 辛苔蒂加股份有限公司 用于脊椎施用的可注射过饱和对乙酰氨基酚溶液
CN104487051A (zh) * 2012-06-29 2015-04-01 辛苔蒂加股份有限公司 用于脊椎施用的可注射过饱和对乙酰氨基酚溶液
US11344517B2 (en) * 2012-06-29 2022-05-31 Sintetica S.A. Injectable supersaturated acetaminophen solution for spinal administration
EA028075B1 (ru) * 2014-04-29 2017-10-31 Мыкола Ивановыч ГУМЕНЮК Фармацевтическая композиция
WO2016156147A1 (fr) 2015-03-27 2016-10-06 Grünenthal GmbH Formulation stable pour l'administration parentérale de tapentadol
EP3479823A1 (fr) 2015-03-27 2019-05-08 Grünenthal GmbH Formulation stable pour l'administration parenterale de tapentadol
US11013701B2 (en) 2015-03-27 2021-05-25 Grünenthal GmbH Stable formulation for parenteral administration of tapentadol
WO2018055070A1 (fr) 2016-09-23 2018-03-29 Grünenthal GmbH Formulation stable pour l'administration parentérale de tapentadol
US10898452B2 (en) 2016-09-23 2021-01-26 Gruenenthal Gmbh Stable formulation for parenteral administration of Tapentadol

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DE10112325A1 (de) 2002-10-02
AU2002254942A1 (en) 2002-09-24
WO2002072080A3 (fr) 2002-11-28

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