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WO2005011665A1 - Utilisation de proglumide pour le traitement des vomissements - Google Patents

Utilisation de proglumide pour le traitement des vomissements Download PDF

Info

Publication number
WO2005011665A1
WO2005011665A1 PCT/GB2004/003169 GB2004003169W WO2005011665A1 WO 2005011665 A1 WO2005011665 A1 WO 2005011665A1 GB 2004003169 W GB2004003169 W GB 2004003169W WO 2005011665 A1 WO2005011665 A1 WO 2005011665A1
Authority
WO
WIPO (PCT)
Prior art keywords
use according
condition
drug
proglumide
emesis
Prior art date
Application number
PCT/GB2004/003169
Other languages
English (en)
Inventor
Robin Mark Bannister
Alan Rothaul
Original Assignee
Arakis Ltd.
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
Priority claimed from GB0317135A external-priority patent/GB0317135D0/en
Priority claimed from GB0324208A external-priority patent/GB0324208D0/en
Priority claimed from GB0413845A external-priority patent/GB0413845D0/en
Application filed by Arakis Ltd. filed Critical Arakis Ltd.
Publication of WO2005011665A1 publication Critical patent/WO2005011665A1/fr

Links

Classifications

    • 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
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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

  • the present invention relates to the treatment of emesis.
  • Nausea the urge to vomit
  • emesis the act of forcibly ejecting the stomach contents through the oesophagus and out of the mouth
  • emesis the act of forcibly ejecting the stomach contents through the oesophagus and out of the mouth
  • AVP arginine vasopressin
  • cholescystokinin is a potent stimulus for the release of AVP (Calegro et al, Neuroendocrinology 1993, and Abelson, Neuropsychopharmacology 2001 ). Proglumide, i.e.
  • 4-(benzoylamino)-5-(dipropylamino)-5-oxopentanoic acid is a cholecystokin antagonist which is licensed for the treatment of gastritis (stomach ulceration).
  • gastritis gastritis
  • H 2 antagonists and proton pump inhibitors The pharmacology of proglumide is known as a mixed CCK A (gastrin) and CCK ⁇ antagonist and its anti- ulceration action is via the inhibition of the CCK A receptor.
  • the present invention is based on the discovery that proglumide possesses anti-nausea and antiemetic activity.
  • a product comprises proglumide and a proemetic drug as a combined product for simultaneous, separate or sequential use in therapy associated with the intended use of the proemetic drug.
  • Proglumide has an asymmetrically substituted carbon atom.
  • the presence of this asymmetric centre gives rise to stereoisomers, and the invention is to be understood to extend to all such stereoisomers, including enantiomers (R or S, substantially free of the other) and diastereoisomers, and mixtures including racemic mixtures thereof.
  • the active agent may be in free or salt form, or given as a prodrug or metabolite.
  • Salts of compounds according to the invention include pharmaceutically acceptable salts, for example acid addition salts derived from inorganic or organic acids, such as hydrochlorides, hydrobromides, p- toluenesulphonates, phosphates, sulphates, perchlorates, acetates, trifluoroacetates, propionates, citrates, malonates, succinates, lactates, oxalates, tartrates and benzoate.
  • Proglumide is useful to treat emesis caused by the administration of another, proemetic drug. In one aspect of the invention, proglumide is used when emesis is observed. In another it is administered prophylactically, in combination with a proemetic drug.
  • the active agent is used in therapy, for the treatment (including prevention) of nausea, dizziness, blurred vision or emesis, including, but not limited to, acute, delayed, post-operative, last-phase and anticipatory emesis.
  • This condition may be associated with (or caused by) various pain conditions such as dysmenorrhoea, migraine, cancer or pancreatitis.
  • This condition may be induced by, for example, chemotherapy, radiation, toxins, pregnancy, alcohol withdrawal, nicotine withdrawal, drug withdrawal, vestibular disorder, motion, post-operative sickness, surgery, gastrointestinal obstruction, reduced gastrointestinal motility, dysmenorrhoea, visceral pain, migraine, increased or decreased intracranial pressure, depression or opioid analgesics.
  • proglumide may be used to treat emesis caused by certain pro-emetic drugs such as antidepressants (examples including amitriptyline, imipramine, desipramine, venlafaxine, citalopram, trazadone, paroxetine, nefazodone, nefopam, fluoxetine and (S)-citalopram), anticonvulsants (examples including lamotrigine, gabapentin and carbamezepine), antipsychotics (examples including clozapine, chlorpromazine, fluphenazine, haloperidol and loxapine) anxiolytics (examples including buspirone and lorazepam), anti-Parkinson's agents (examples including apomorphine, pergolide, levodopa, dopamine naxagolide, bromocriptine and amantadine), CNS stimulants (examples including
  • Such a proemetic agent and progumide may be administered simultaneously, sequentially or separately, e.g. in combination.
  • the active agent may also be used according to the invention when the patient is also being given another anti-emetic agent.
  • agents include phenothiazines, 5HT3 receptor antagonists, dopamine antagonists, anticholinergic agents, anti-histamines, histamine analogues, cannabinoids, corticosteroids, GABA receptor antagonists, NK1 receptor antagonists, ⁇ 2 and 0 3 adrenoceptor antagonists, and SNRis.
  • these types of compounds are cyclizine, dolasetron, granisetron, ondansetron, tropisetron, nabilone, scopolenine, cinnerizine, promethazine, betahistine, dexamethasome, methylprednisolone, metoclopramide, chlorpromazine, perphenazine, prochlorperazine, thiethylperazine, droperidol, domperidone and haloperidol.
  • Such an agent and proglumide may be administered simultaneously, sequentially or separately, e.g. in combination.
  • the active agent may be administered orally, topically, parenterally, by inhalation or nasal spray or rectally in dosage unit formulations containing non- toxic pharmaceutically acceptable carriers, adjuvants and vehicles.
  • the composition may be in controlled release form or have an enteric coating.
  • parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrastemal injection or infusion techniques.
  • the compounds of the invention are effective in the treatment of humans.
  • the dose of the active agent will depend on the nature and degree of the condition, the age and condition of the patient, and other factors known to those skilled in the art.
  • a typical dosage for a human patient is 1 to 200, e.g. 10 to 100, mg given one to three times per day.
  • a Study illustrating the invention will now be described. The Study investigated the anti-emetic effect of proglumide against cisplatin-induced emesis in piglets. Study Details of the animal preparation have been described previously (Grelot etal., 1996 ; Grelot etal., 1998 ; Girod etal., 2002). The series of investigations was performed on weaned purebred (Pietrain, Hampshire) or crossbred (Pietrain X Hampshire) piglets (40-70 days old), of either sex, weighing approximately 7- 11 kg.
  • Piglets isolated in individual boxes (0.7 m 3 ), were then allowed 3-4 days recovery before commencement of vomiting experiments, and were fed daily with 400-500 g of a solid commercial diet (9500 kJ/kg; Sofetac, Cenord) and water ad libitum.
  • the experimental procedures were carried out in accordance with European Council Directive 86/609/EEC. Every effort was made to minimize the animals' suffering and to reduce the number of animals used in the experiments. Piglets included in these experiments were naive to previous administration of cytotoxic, anti-emetic drugs and of any other emetic challenges.
  • the animals were treated with vehicle (NaCI 0.9%) or proglumide (0,3 , 3 or 30 mg/kg dissolved in NaCI 0.9%). Both treatments were administered 10 minutes before cisplatin treatment administered peros.
  • the protocol of drug administration including the numbers of piglets given each treatment, are given in the following table.

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)
  • Otolaryngology (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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne l'utilisation de proglumide qui est utile dans le traitement d'une condition choisie parmi la nausée, les vertiges, la vision trouble et les vomissements. Cette condition peut être induite par des médicaments.
PCT/GB2004/003169 2003-07-22 2004-07-22 Utilisation de proglumide pour le traitement des vomissements WO2005011665A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB0317135A GB0317135D0 (en) 2003-07-22 2003-07-22 The treatment of emesis
GB0317135.2 2003-07-22
GB0324208.8 2003-10-15
GB0324208A GB0324208D0 (en) 2003-10-15 2003-10-15 The treatment of emesis
GB0413845.9 2004-06-21
GB0413845A GB0413845D0 (en) 2004-06-21 2004-06-21 The treatment of emesis

Publications (1)

Publication Number Publication Date
WO2005011665A1 true WO2005011665A1 (fr) 2005-02-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2004/003169 WO2005011665A1 (fr) 2003-07-22 2004-07-22 Utilisation de proglumide pour le traitement des vomissements

Country Status (1)

Country Link
WO (1) WO2005011665A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009089234A2 (fr) * 2008-01-07 2009-07-16 Auspex Pharmaceuticals Dibenzhydrylpipérazines substituées
WO2009143572A1 (fr) * 2008-05-27 2009-12-03 The University Of Melbourne Procédés de traitement de mammifères souffrant de dysfonctionnements de la trompe d’eustache
WO2020097054A1 (fr) * 2018-11-06 2020-05-14 Georgetown University Traitement de la stéatohépatite non alcoolique avec des inhibiteurs de la cck
EP4477218A1 (fr) * 2023-06-15 2024-12-18 Universitat Autònoma de Barcelona Antagoniste de la cholécystokinine (cck) destiné à être utilisé dans la prévention et/ou le traitement d'une maladie ou d'un trouble vestibulaire

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4576951A (en) * 1983-12-12 1986-03-18 Rotta Research Laboratorium S.P.A. Proglumide, pharmaceutical preparations and compositions including it for use in human pain relief
US4978683A (en) * 1984-12-27 1990-12-18 Rotta Research Laboratorium S.P.A. Proglumide and pharmaceutical compositions containing it for use in the treatment of neoplastic affections
EP0669334A1 (fr) * 1992-11-11 1995-08-30 Fujisawa Pharmaceutical Co., Ltd. Compose tricyclique
US5760032A (en) * 1994-06-01 1998-06-02 Yoshitomi Pharmaceutical Industries, Ltd. Thienylazole compound and thienotriazolodiazepine compound
WO2002085355A1 (fr) * 2001-04-18 2002-10-31 Euro-Celtique, S.A. Composes de spiropyrazole

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4576951A (en) * 1983-12-12 1986-03-18 Rotta Research Laboratorium S.P.A. Proglumide, pharmaceutical preparations and compositions including it for use in human pain relief
US4978683A (en) * 1984-12-27 1990-12-18 Rotta Research Laboratorium S.P.A. Proglumide and pharmaceutical compositions containing it for use in the treatment of neoplastic affections
EP0669334A1 (fr) * 1992-11-11 1995-08-30 Fujisawa Pharmaceutical Co., Ltd. Compose tricyclique
US5760032A (en) * 1994-06-01 1998-06-02 Yoshitomi Pharmaceutical Industries, Ltd. Thienylazole compound and thienotriazolodiazepine compound
WO2002085355A1 (fr) * 2001-04-18 2002-10-31 Euro-Celtique, S.A. Composes de spiropyrazole

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
"Blockade of gastrin receptors by proglumide in peptic ulcer", MEDIZINISCHE KLINIK 1980 GERMANY, vol. 75, no. 18, 1980, pages 7 - 8, XP008037663 *
CSERNANSKY J G ET AL: "DIFFERENTIAL EFFECTS OF PROGLUMIDE ON MESOLIMBIC AND NIGROSTRIATAL DOPAMINE FUNCTION", PSYCHOPHARMACOLOGY, vol. 91, no. 4, 1987, pages 440 - 444, XP008037912, ISSN: 0033-3158 *
FEINLE C ET AL: "Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid.", GASTROENTEROLOGY. MAY 1996, vol. 110, no. 5, May 1996 (1996-05-01), pages 1379 - 1385, XP008037661, ISSN: 0016-5085 *
FEINLE C: "Role of intestinal chemoreception in the induction of gastrointestinal sensations.", DTW. DEUTSCHE TIERARZTLICHE WOCHENSCHRIFT. DEC 1998, vol. 105, no. 12, December 1998 (1998-12-01), pages 441 - 444, XP008037669, ISSN: 0341-6593 *
FIELD M J ET AL: "Combination of morphine and proglumide leads to synergy in a rat model of neuropathic pain", EUROPEAN JOURNAL OF NEUROSCIENCE, vol. 12, no. Supplement 11, 2000, & MEETING OF THE FEDERATION OF EUROPEAN NEUROSCIENCE SOCIETIES; BRIGHTON, UK; JUNE 24-28, 2000, pages 69, XP008037917, ISSN: 0953-816X *
LANG I M ET AL: "Comparison of gastrointestinal responses to CCK-8 and associated with vomiting", AMERICAN JOURNAL OF PHYSIOLOGY - GASTROINTESTINAL AND LIVER PHYSIOLOGY 1988 UNITED STATES, vol. 254, no. 2, 1988, pages 17/2, XP008037667, ISSN: 0002-9513 *
MELEN-MUCHA G: "Effects of short term treatment with pentagastrin, proglumide, tamoxifen given separately or together with 5-fluorouracil on the growth in the murine transplantable Colon 38 cancer", NEOPLASMA (BRATISLAVA), vol. 48, no. 2, 2001, pages 133 - 138, XP008037913, ISSN: 0028-2685 *
SCARPIGNATO C: "CHOLECYSTOKININ ANTAGONISTS AND MOTILIDES PHARMACOLOGY AND POTENTIAL IN THE TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE AND OTHER DIGESTIVE MOTOR DISORDERS", SCARPIGNATO, C. (ED.). FRONTIERS OF GASTROINTESTINAL RESEARCH, VOL. 20. ADVANCES IN DRUG THERAPY OF GASTROESOPHAGEAL REFLUX DISEASE. XIII+371P. S. KARGER AG: BASEL, SWITZERLAND; NEW YORK, NEW YORK, USA. ILLUS SERIES : FRONTIERS OF GASTROINTESTINAL RE, 1992, pages 90 - 128, XP008037668, ISSN: 3-8055-5360-9 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009089234A2 (fr) * 2008-01-07 2009-07-16 Auspex Pharmaceuticals Dibenzhydrylpipérazines substituées
WO2009089234A3 (fr) * 2008-01-07 2009-10-08 Auspex Pharmaceuticals Dibenzhydrylpipérazines substituées
WO2009143572A1 (fr) * 2008-05-27 2009-12-03 The University Of Melbourne Procédés de traitement de mammifères souffrant de dysfonctionnements de la trompe d’eustache
US8642631B2 (en) 2008-05-27 2014-02-04 University Of Melbourne Methods of treating mammals with eustachian tube dysfunctions
AU2009253739B2 (en) * 2008-05-27 2014-02-06 Otolanum Ag Methods of treating mammals with eustachian tube dysfunctions
EA022565B1 (ru) * 2008-05-27 2016-01-29 Дзе Юниверсити Оф Мельбурн Способы лечения млекопитающих с дисфункциями евстахиевой трубы
WO2020097054A1 (fr) * 2018-11-06 2020-05-14 Georgetown University Traitement de la stéatohépatite non alcoolique avec des inhibiteurs de la cck
US12251364B2 (en) 2018-11-06 2025-03-18 Georgetown University Treating non-alcoholic steatohepatitis with cck inhibitors
EP4477218A1 (fr) * 2023-06-15 2024-12-18 Universitat Autònoma de Barcelona Antagoniste de la cholécystokinine (cck) destiné à être utilisé dans la prévention et/ou le traitement d'une maladie ou d'un trouble vestibulaire
WO2024256731A3 (fr) * 2023-06-15 2025-02-27 Universitat Autonoma De Barcelona Antagoniste de cholécystokinine (cck) destiné à être utilisé dans la prévention et/ou le traitement d'une maladie ou d'un trouble vestibulaire

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