+

WO2003053427A1 - Utilisation de (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol en tant qu'anti-emetique - Google Patents

Utilisation de (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol en tant qu'anti-emetique Download PDF

Info

Publication number
WO2003053427A1
WO2003053427A1 PCT/EP2002/014636 EP0214636W WO03053427A1 WO 2003053427 A1 WO2003053427 A1 WO 2003053427A1 EP 0214636 W EP0214636 W EP 0214636W WO 03053427 A1 WO03053427 A1 WO 03053427A1
Authority
WO
WIPO (PCT)
Prior art keywords
active ingredient
dimethylamino
ethyl
phenol
methyl
Prior art date
Application number
PCT/EP2002/014636
Other languages
German (de)
English (en)
Inventor
Elmar Friderichs
Wolfgang Strassburger
Ulrich Jahnel
Original Assignee
Grünenthal GmbH
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 Grünenthal GmbH filed Critical Grünenthal GmbH
Priority to AU2002361185A priority Critical patent/AU2002361185A1/en
Publication of WO2003053427A1 publication Critical patent/WO2003053427A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics

Definitions

  • This object is achieved by using (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol in the form of its base or in the form of one of its physiologically tolerable salts and / or Solvate for the manufacture of a medicament for the prevention and / or therapy of nausea and / or vomiting.
  • (+) - (1S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol is also referred to as "active ingredient (I)", which does not only refer to the free base, but also relates to one of its physiologically tolerable salts and / or solvates.
  • dimethylamino-1-ethyl-2-methyl-propyl phenol In contrast to morphine (and many other opioid analgesics), dimethylamino-1-ethyl-2-methyl-propyl) phenol not only does not have an emetic effect, ie does not cause nausea or vomiting, but also has an antiemetic effect, ie the emetic effect of known emesis Triggers like morphine or emetin (Ipecacuanha extract) cancels out. This antiemetic effect is not only found at relatively high doses, but also over the entire dose range examined, i.e. also when small doses are administered. These results are confirmed by tests on ferrets, a standard model for the detection of emetic and antiemetic active properties (see, for example, C.
  • the further antiemetic active ingredient is, in particular, metoclopramide, domperidone, haloperidol, fluphenazine, sulpiride, tiapride, benzoquinamide, diazepam, betamethasone, dexamethasone, prednisolone, cyclizine, hydroxyzine, diphenhydramine, scopolamine, chlorpromazine, promethidolperperol, perphenol Bemesetron and particularly preferably ondansetron, bemesetron, benzapride, zacoprid, dazoprid, p-chlorophenylalanine, granisetron, tropisetron or dolasetron. Most preferred as another antiemetic agent is ondansetron.
  • Another advantage of the present invention is that the active ingredient (I) exhibits its anti-emetic effect even when a cytostatic active ingredient is administered simultaneously, previously or subsequently.
  • a cytostatic active ingredient is administered simultaneously, previously or subsequently.
  • emesis model i.v. of 10 mg / kg cisplatin - agent of choice for the chemotherapy of many cancers - to ferrets by administering (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol (as hydrochloride) suppresses the vomiting usually caused by cisplatin.
  • (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol suitable for the prophylaxis and therapy of nausea and emesis accompanying cancer treatment with cytostatics (chemotherapy).
  • the active ingredient (I) is used as an antiemetic in addition to at least one cytostatic agent.
  • the cytostatic is preferably carboplatin,
  • Doxorubicin, cyclophosphamide, taxol or especially cisplatin Doxorubicin, cyclophosphamide, taxol or especially cisplatin.
  • compositions for the prophylaxis and / or therapy of nausea and / or vomiting containing (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) ) phenol in the form of its base or in the form of one of its physiologically acceptable salts and / or solvates and one or more pharmaceutical adjuvants.
  • compositions preferably comprise at least one further active ingredient for the prevention and / or therapy of nausea and / or vomiting.
  • a suitable further antiemetic active ingredient is preferably selected from the following active ingredient groups: dopamine antagonists, benzodiazepines, corticosteroids, antihistamines, anticholinergics, phenothiazines, butyrophenones, benzamides and in particular 5-HT 3 antagonists.
  • dopamine antagonists preferably selected from the following active ingredient groups: dopamine antagonists, benzodiazepines, corticosteroids, antihistamines, anticholinergics, phenothiazines, butyrophenones, benzamides and in particular 5-HT 3 antagonists.
  • dopamine antagonists preferably selected from the following active ingredient groups: dopamine antagonists, benzodiazepines, corticosteroids, antihistamines, anticholinergics, phenothiazines, butyrophenones, benzamides and in particular
  • the active substance is in particular metoclopramide, domperidone, haloperidol, fluphenazine, sulpiride, tiapride, benzoquinamide, diazepam, betamethasone, dexamethasone, prednisolone, cyclizine, hydroxyzine, diphenhydramine, scopolamine, chlorpromazine, promethazine, perphenazine, prochlorperazine, particularly preferred, drochloronazine, prochlorperazine around ondansetron, bemesetron, benzapride, zacoprid, dazopride, p-chlorophenylalanine, granisetron, tropisetron or dolasetron. Most preferred as another antiemetic agent is ondansetron.
  • this additionally comprises an opioid.
  • This additional opioid active ingredient is preferably selected from the group comprising morphine, hydromorphone, fentanyl, buprenorphine, tilidine and tramadol.
  • Pharmaceutically acceptable salts or physiologically acceptable salts in the sense of this invention are such salts of the active ingredient (+) - (1S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol, which are used in pharmaceutical applications physiologically - especially when used on mammals and / or humans - are compatible.
  • Such pharmaceutically acceptable salts can be formed, for example, with inorganic or organic acids.
  • Hydrochloride formation is particularly preferred, which can be brought about, for example, by adding trimethylsilyl chloride (TMSCI) to the active ingredient base (I) dissolved in a suitable organic solvent.
  • TMSCI trimethylsilyl chloride
  • the active ingredient (I) and its physiologically acceptable salts can also be present as solvates, in particular hydrates; the hydrates can be obtained, for example, by crystallization from an aqueous solution.
  • auxiliaries such as carrier materials, fillers, solvents, diluents, surface-active substances, dyes, preservatives, disintegrants, lubricants, lubricants, flavors and / or binders.
  • auxiliaries can be, for example: water, ethanol, 2-propanol, glycerol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, glucose, fructose, lactose, sucrose, dextrose, molasses, starch, modified starch, gelatin, Sorbitol, inositol, mannitol, microcrystalline cellulose, methyl cellulose, carboxymethyl cellulose, cellulose acetate, shellac, cetyl alcohol, polyvinyl pyrrolidone, paraffins, waxes, natural and synthetic gums, acacia gum, alginates, dextran, saturated and unsaturated fatty acids, stearate, stearate,
  • Silicon dioxide titanium oxide, titanium dioxide, magnesium sulfate, zinc sulfate, calcium sulfate, potash, calcium phosphate, dicalcium phosphate, potassium bromide, potassium iodide, talc, kaolin, pectin, crospovidone, agar and bentonite.
  • excipients and the amounts to be used depends on whether the medicament is to be administered orally, subcutaneously, parenterally, intravenously, pulmonally, intraperitoneally, transdermally, intramuscularly, nasally, buccally, rectally or in another suitable manner.
  • the following are suitable for oral application: Preparations in the form of tablets, dragees, capsules, granules, drops, juices and syrups, for parenteral, topical and inhalation application solutions, suspensions, easily reconstitutable powders for inhalation and sprays.
  • the active ingredient (I) is e.g. in a depot in dissolved form or in a plaster, optionally with the addition of agents which promote skin penetration.
  • compositions according to the invention which, in addition to (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol, in The form of its base or in the form of one of its physiologically tolerable salts and / or solvates, a further antiemetic or an additional opioid or an additional cytostatic agent, can be designed in such a way that these combination preparations release the active compounds present at the same time or almost simultaneously, or control the release in such a way that one of the active ingredients, for example the additional opioid or the additional cytostatic agent, is released and the release of the other active ingredient, for example the active ingredient (I), is delayed, ie occurs later, in order to achieve the desired effect of all active ingredients contained in the composition
  • the medicaments and pharmaceutical compositions according to the invention are produced with the aid of means, devices, methods and processes which are well known in the art of pharmaceutical formulation, as described, for example, in "Remington 's Pharmaceutical Sciences", published by AR Gennaro, 17th Ed., Mack Publishing Company, Easton, Pa. (1985), in particular in Part 8, Chapters 76 to 93.
  • a solid formulation such as a tablet
  • the active ingredient of the drug ie (+) - (1 S, 2S) -3- (3-dimethylamino-1-ethyl-2-methyl-propyl) phenol or one of its physiologically acceptable salts and / or solvates
  • a pharmaceutical carrier for example conventional tablet ingredients, such as corn starch, lactose, sucrose, sorbitol, talc, magnesium stearate, dicalcium phosphate or pharmaceutically acceptable gums
  • pharmaceutical diluents such as water, for example, granulated to give a solid Form composition comprising a compound of the invention or a pharmaceutically acceptable Contains salt in a homogeneous distribution.
  • a homogeneous distribution is understood here to mean that the active ingredient is uniformly distributed over the entire composition, so that it can be easily divided into equally effective unit dose forms, such as tablets, pills or capsules.
  • the solid composition is then divided into unit dose forms.
  • the tablets or pills of the medicament according to the invention or of the compositions according to the invention can also be coated or compounded in some other way in order to provide a dosage form with delayed release.
  • Suitable coating agents include polymeric acids and mixtures of polymeric acids with materials such as shellac, cetyl alcohol and / or cellulose acetate.
  • Another object of the invention relates to a method for the treatment of emesis and / or nausea in a mammal and / or human, which is characterized in that a therapeutically effective amount of the active ingredient (I) in the form of its base or in the form of one of its physiologically tolerable Salts and / or solvates, optionally in combination with a further antiemetic or an additional opioid or an additional cytostatic agent, is administered.
  • the amount of active ingredient to be administered to the patient varies and depends on the weight, age and history of the patient, as well as on the type of application, the indication and the severity of the disease. Usually 0.1 to 1000 mg, in particular 1 to 100 mg, preferably 2 to 50 mg of the active ingredient (I) are applied.
  • Morphin HCI (RBI Batch 2883/6) in a dose of 0.1 mg / kg i.v. or Ipecacuanha fluid extract, DAC 98 (adjusted to 2% emetin) from Synpharm (batch 9906B067) orally administered according to a dose of 2 mg / kg emetin.
  • test result is shown as the group mean (x ⁇ sx) of the events in the reacting animals.
  • percentage of animals with retches and vomits is also calculated.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Utilisation de (+)-(1S,2S)-3-(3-diméthylamino-1-éthyl-2-méthyl-propyl)phénol pour la fabrication d'un anti-émétique et compositions pharmaceutiques à action anti-émétique qui contiennent, outre une ou plusieurs adjuvants pharmaceutiques, du (+)-1S,2S)-3-(3-diméthylamino-1-éthyl-2-méthyl-propyl)phénol en tant que principe actif et éventuellement une autre principe actif médicamenteux.
PCT/EP2002/014636 2001-12-21 2002-12-20 Utilisation de (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol en tant qu'anti-emetique WO2003053427A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002361185A AU2002361185A1 (en) 2001-12-21 2002-12-20 Use of (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol as anti-emetic agent

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10163421A DE10163421A1 (de) 2001-12-21 2001-12-21 Verwendung von (+)-(1S,2S)-3-(3-Dimethylamino-1-ethyl-2-methyl-propyl)phenol als Antiemetikum
DE10163421.8 2001-12-21

Publications (1)

Publication Number Publication Date
WO2003053427A1 true WO2003053427A1 (fr) 2003-07-03

Family

ID=7710471

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2002/014636 WO2003053427A1 (fr) 2001-12-21 2002-12-20 Utilisation de (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol en tant qu'anti-emetique

Country Status (3)

Country Link
AU (1) AU2002361185A1 (fr)
DE (1) DE10163421A1 (fr)
WO (1) WO2003053427A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005013726A1 (de) * 2005-03-22 2006-09-28 Grünenthal GmbH Transdermale therapeutische Systeme mit verbesserter Verträglichkeit
WO2011157391A1 (fr) * 2010-06-15 2011-12-22 Grünenthal GmbH Combinaison pharmaceutique pour le traitement de la douleur
WO2013017233A1 (fr) * 2011-07-29 2013-02-07 Grünenthal GmbH Administration intrathécale ou épidurale de 3-[(1s,2s)-3-(diméthylamino)-1-éthyl-2-méthyl-propyl]-phénol
EP2796171A1 (fr) * 2010-03-11 2014-10-29 Acacia Pharma Limited Utilisation de l'amisulpride pour le traitement des nausées et vomissements induits par les opiacés
AU2014202535B2 (en) * 2010-03-11 2016-05-26 Acacia Pharma Limited The use of amisulpride as an anti-emetic
AU2016216578B2 (en) * 2010-03-11 2017-11-23 Acacia Pharma Limited The use of amisulpride as an anti-emetic
US12005042B2 (en) 2017-02-10 2024-06-11 Acacia Pharma Ltd. Rescue treatment of post operative nausea and vomiting

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0693475A1 (fr) * 1994-07-23 1996-01-24 Grünenthal GmbH Dérivés propane 1-phényl-3-diméthylamino à activité pharmocologique
WO2002067916A2 (fr) * 2001-02-28 2002-09-06 Grünenthal GmbH Sels pharmaceutiques

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0693475A1 (fr) * 1994-07-23 1996-01-24 Grünenthal GmbH Dérivés propane 1-phényl-3-diméthylamino à activité pharmocologique
WO2002067916A2 (fr) * 2001-02-28 2002-09-06 Grünenthal GmbH Sels pharmaceutiques
WO2002067651A2 (fr) * 2001-02-28 2002-09-06 Grünenthal GmbH Sels pharmaceutiques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HERRSTEDT J: "Potential new agents in the prophylaxis and treatment of chemotherapy-induced emesis", EUROPEAN JOURNAL OF CANCER, PERGAMON PRESS, OXFORD, GB, vol. 37, no. 7, May 2001 (2001-05-01), pages 823 - 825, XP004233940, ISSN: 0959-8049 *
OETTLE HELMUT ET AL: "Treatment of chemotherapy-induced nausea and vomiting.", JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, vol. 127, no. 6, 2001, pages 340 - 345, XP001146210, ISSN: 0171-5216 *
TRAMER M R: "A rational approach to the control of postoperative nausea and vomiting: Evidence from systematic reviews. Part II. Recommendations for prevention and treatment, and research agenda.", ACTA ANAESTHESIOLOGICA SCANDINAVICA, vol. 45, no. 1, January 2001 (2001-01-01), pages 14 - 19, XP001146209, ISSN: 0001-5172 *

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005013726A1 (de) * 2005-03-22 2006-09-28 Grünenthal GmbH Transdermale therapeutische Systeme mit verbesserter Verträglichkeit
US9119836B2 (en) 2010-03-11 2015-09-01 Acacia Pharma Limited Use of amisulpride as an anti-emetic
US12194022B2 (en) 2010-03-11 2025-01-14 Acacia Pharma Limited Use of amisulpride as an anti-emetic
US10525033B2 (en) 2010-03-11 2020-01-07 Acacia Pharma Limited Use of amisulpride as an anti-emetic
US10085970B2 (en) 2010-03-11 2018-10-02 Acacia Pharma Limited Use of amisulpride as an anti-emetic
US9889118B2 (en) 2010-03-11 2018-02-13 Acacia Pharma Limited Use of amisulpride as an anti-emetic
AU2016216578B2 (en) * 2010-03-11 2017-11-23 Acacia Pharma Limited The use of amisulpride as an anti-emetic
US9545426B2 (en) 2010-03-11 2017-01-17 Acacia Pharma Limited Use of amisulpride as an anti-emetic
EP2796171A1 (fr) * 2010-03-11 2014-10-29 Acacia Pharma Limited Utilisation de l'amisulpride pour le traitement des nausées et vomissements induits par les opiacés
AU2014202535B2 (en) * 2010-03-11 2016-05-26 Acacia Pharma Limited The use of amisulpride as an anti-emetic
US9084765B2 (en) 2010-03-11 2015-07-21 Acacia Pharma Limited Use of amisulpride as an anti-emetic
EP2992877A1 (fr) * 2010-06-15 2016-03-09 Grünenthal GmbH Combinaison pharmaceutique pour le traitement de la douleur
RU2675261C2 (ru) * 2010-06-15 2018-12-18 Грюненталь Гмбх Фармацевтическая комбинация для лечения от боли
WO2011157391A1 (fr) * 2010-06-15 2011-12-22 Grünenthal GmbH Combinaison pharmaceutique pour le traitement de la douleur
AU2011267474B2 (en) * 2010-06-15 2016-05-26 Grünenthal GmbH Pharmaceutical combination for the treatment of pain
US8846765B2 (en) 2010-06-15 2014-09-30 Gruenenthal Gmbh Pharmaceutical combination
US10813890B2 (en) 2010-06-15 2020-10-27 Grünenthal GmbH Pharmaceutical combination
JP2013528629A (ja) * 2010-06-15 2013-07-11 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 痛み治療用の医薬配合物
CN103108631B (zh) * 2010-06-15 2015-08-26 格吕伦塔尔有限公司 用于治疗疼痛的联合药物
AU2016219643B2 (en) * 2010-06-15 2018-04-12 Grünenthal GmbH Pharmaceutical combination for the treatment of pain
CN103108631A (zh) * 2010-06-15 2013-05-15 格吕伦塔尔有限公司 用于治疗疼痛的联合药物
EP3300726A1 (fr) * 2011-07-29 2018-04-04 Grünenthal GmbH Administration intrathécale ou épidurale de 3-[(1s, 2s)-3- (diméthylamino)-1-éthyl-2-méthylpropyl] phénol
WO2013017233A1 (fr) * 2011-07-29 2013-02-07 Grünenthal GmbH Administration intrathécale ou épidurale de 3-[(1s,2s)-3-(diméthylamino)-1-éthyl-2-méthyl-propyl]-phénol
JP2014524924A (ja) * 2011-07-29 2014-09-25 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング ３−［（１ｓ，２ｓ）−３−（ジメチルアミノ）−１−エチル−２−メチルプロピル］フェノールのくも膜下投与または硬膜外投与
US8895623B2 (en) 2011-07-29 2014-11-25 Gruenenthal Gmbh Intrathecal or epidural administration of 3-[(1S,25)-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol
US12005042B2 (en) 2017-02-10 2024-06-11 Acacia Pharma Ltd. Rescue treatment of post operative nausea and vomiting

Also Published As

Publication number Publication date
AU2002361185A1 (en) 2003-07-09
DE10163421A1 (de) 2003-07-31

Similar Documents

Publication Publication Date Title
DE69231395T3 (de) Neue medizinische Indikation für Tachykinin-Antagonisten
DE69523295T2 (de) Nasale und okulare anwendung von ketamin zur schmerzbeherrschung und entgiftung
DE60009346T2 (de) Buprenorphin enthaltende analgetische zusammensetzungen
DE2523998A1 (de) Pharmazeutische zubereitung fuer die behandlung der schizophrenie
EP2857013A1 (fr) Tapentadol destiné au traitement de la douleur arthrosique
EP1397138A2 (fr) Association de principes actifs destinee au traitement medicamenteux d'une intoxication a des substances entrainant une dependance ou a des stupefiants
WO2006087160A1 (fr) Procede de traitement medicamenteux combine et combinaisons medicamenteuses destinees a cet effet
DE102007018150A1 (de) VR1-Rezeptor-Liganden und µ-Opioid-Rezeptor-Liganden zur Behandlung von Schmerz
DE3687575T2 (de) Verwendung von 6-methylen-6-desoxy-n-cyclopropylmethyl-14-hydroxydihydronormorphin.
WO2003053427A1 (fr) Utilisation de (+)-(1s,2s)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol en tant qu'anti-emetique
DE69209140T2 (de) Verwendung Glycine/NMDA-Rezeptorliganden zur Herstellung eines Arzneimittels zur Behandlung von Drogenabhängigkeit und Entzugserscheinungen
DE69625913T2 (de) Inhibitor des erwerbs der abhängigkeit/resistenz gegen betäaubende analgetika
EP1337254B1 (fr) Utilisation d'opioides faibles et d'agonistes/d'antagonistes opioides melanges pour traiter l'incontinence urinaire
DE3445183A1 (de) Proglumide enthaltende arzneimittel mit analgetischer wirkung
DE69814089T2 (de) Verwendung von einem draflazin analog zur schmerzbehandlung
EP1368023B1 (fr) Utilisation de buprenorphine pour traiter l'incontinence d'urine
DE69330638T2 (de) Verwendung von 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine zur herstrllung eines medikaments zur behandlung von bestimmten schmerzen und ödem
DE19540642A1 (de) Verwendung von Inhibitoren der Phosphodiesterase bei der Behandlung von Prostataerkrankungen
WO2000048582A2 (fr) Composition pharmaceutique contenant de la desoxypeganine utilisee pour le traitement de la toxicomanie
EP1337246B1 (fr) Utilisation de composes 6-dimethylaminomethyle-1-phenyl-cyclohexane pour traiter l'incontinence urinaire
EP2120918B1 (fr) Composition pharmaceutique pour le traitement de l'incontinence
DE602004008440T2 (de) Pharmazeutische kombinationspräparat zur behandlung von spastischkeit und/oder schmerzen
DE69831959T2 (de) Verwendung von (E)-metanicotinederivate als Analgetika
DE2810051A1 (de) Zubereitung fuer die behandlung von asthma
EP0870499A1 (fr) Utilisation orale du (+)-0-déméthyltramadol comme analgésique

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载