WO1998025594A2 - Nouveau traitement - Google Patents

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Publication number
WO1998025594A2
WO1998025594A2 PCT/EP1997/006971 EP9706971W WO9825594A2 WO 1998025594 A2 WO1998025594 A2 WO 1998025594A2 EP 9706971 W EP9706971 W EP 9706971W WO 9825594 A2 WO9825594 A2 WO 9825594A2
Authority
WO
WIPO (PCT)
Prior art keywords
lamotrigine
migraine
pharmaceutically acceptable
treatment
acceptable salt
Prior art date
Application number
PCT/EP1997/006971
Other languages
English (en)
Other versions
WO1998025594A3 (fr
Inventor
John Morris Evans
Andrew Parsons
Original Assignee
Smithkline Beecham Plc
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 Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to JP52623998A priority Critical patent/JP2001510461A/ja
Priority to CA002274858A priority patent/CA2274858A1/fr
Priority to EP97953793A priority patent/EP0948325A2/fr
Publication of WO1998025594A2 publication Critical patent/WO1998025594A2/fr
Publication of WO1998025594A3 publication Critical patent/WO1998025594A3/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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • 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
    • A61P25/06—Antimigraine agents

Definitions

  • EP-0021121 (Buroughs Wellcome) describes a class of compounds which are described as being useful for the treatment and/or prevention of epilepsy.
  • One particular compound described therein is 3,5-diamino-6-(2,3-dichlorophenyl)-l,2,4-triazine which is better know as lamotrigine.
  • lamotrigine is particularly useful for treating and/or preventing migraine. Accordingly, the present invention provides the use of lamotrigine and/or pharmaceutically acceptable salts thereof in the manufacture of a medicament in the treatment and/or prevention of migraine.
  • Lamotrigine and/or pharmaceutically acceptable salts thereof may be prepared according to the procedures described in EP-0 021 121.
  • the administration to a sufferer in need thereof may be by way of oral (including sub-lingual) or parenteral administration.
  • a unit dose will normally contain 1 to 1000 mg, suitably 1 to 500 mg, for example an amount in the range of from 2 to 400 mg such as 2, 5, 10, 20, 30, 40, 50, 100, 200, 300 and 400 mg of the active compound.
  • Unit doses will normally be administered once or more than once per day, for example 1, 2, 3, 4, 5 or 6 times a day, more usually 1 to 4 times a day, such that the total daily dose is normally in the range, for a 70 kg adult of 1 to 1000 mg, for example 1 to 500 mg, that is in the range of approximately 0.01 to 15 mg/kg/day, more usually 0.1 to 6 mg/kg/day, for example 1 to 6 mg/kg/day.
  • lamotrigine is administered in the form of a unit-dose composition, such as a unit dose oral (including sub-lingual), rectal, topical or parenteral (especially intravenous) composition.
  • a unit dose oral (including sub-lingual), rectal, topical or parenteral (especially intravenous) composition Such compositions are prepared by admixture and are suitably adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories.
  • Orally administrable compositions are preferred, in particular shaped oral compositions, since they are more convenient for general use.
  • Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents.
  • the tablets may be coated according to well known methods in the art.
  • Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
  • Suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycollate.
  • Suitable lubricants include, for example, magnesium stearate.
  • Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
  • solid oral compositions may be prepared by conventional methods of blending, filling, tabletting or the like. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are, of course, conventional in the art.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl jt?-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • suspending agents for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats, emulsifying agents, for example lecithin, sorbitan monoo
  • Oral formulations also include conventional sustained release formulations, such as tablets or granules having an enteric coating.
  • fluid unit dose forms are prepared containing the compound and a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
  • the compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
  • the present invention further provides a pharmaceutical composition for use in the treatment and/or prophylaxis of migraine which comprises lamotrigine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • the invention provides a method for the treatment and/or prophylaxis of migraine which comprises administrating an effective or prophylactic amount of lamotrigine to a sufferer in need thereof.
  • compositions may be prepared in the manner as hereinbefore described.
  • the following pharmacological data demonstrates the present invention.
  • CSD was induced by administration of a small quantity (30 mg crystal) of KC1 to a region of the suprasylvian gyrus distant from recording electrodes, vessels under observation and other blood vessels.
  • KC1 dissolves slowly into the brain for the 6 min period of application.
  • the remaining KCl was washed from the brain surface with a saline swab. Changes in extracellular potential and in artery and vein diameter were then recorded for a period of up to 120 min.
  • the compound lamotrigine (10 mg/kg, i.p.) or vehicle (labrasol i.p.) was administered 90 min before CSD induction.
  • Bipolar stainless electrodes were stereotaxically placed into each trigeminal ganglion.
  • Guanethidine (3 mg/kg i.v.) was then administered and 45 min allowed for stabilisation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (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)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (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)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne un procédé de traitement ou de prévention de la migraine chez l'humain. Le procédé consiste à administrer à un patient souffrant de la migraine une quantité effective de lamotrigine ou un sel pharmaceutiquement acceptable dudit produit.
PCT/EP1997/006971 1996-12-12 1997-12-09 Nouveau traitement WO1998025594A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP52623998A JP2001510461A (ja) 1996-12-12 1997-12-09 偏頭痛の治療および予防におけるラモトリジン
CA002274858A CA2274858A1 (fr) 1996-12-12 1997-12-09 Nouveau traitement
EP97953793A EP0948325A2 (fr) 1996-12-12 1997-12-09 Nouveau traitement

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9625795.1A GB9625795D0 (en) 1996-12-12 1996-12-12 Novel treatment
GB9625795.1 1996-12-12

Publications (2)

Publication Number Publication Date
WO1998025594A2 true WO1998025594A2 (fr) 1998-06-18
WO1998025594A3 WO1998025594A3 (fr) 1998-09-17

Family

ID=10804309

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/006971 WO1998025594A2 (fr) 1996-12-12 1997-12-09 Nouveau traitement

Country Status (5)

Country Link
EP (1) EP0948325A2 (fr)
JP (1) JP2001510461A (fr)
CA (1) CA2274858A1 (fr)
GB (1) GB9625795D0 (fr)
WO (1) WO1998025594A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7709523B2 (en) 2003-01-16 2010-05-04 Newron Pharmaceuticals Spa Alpha-aminoamide derivatives useful as antimigraine agents

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100882707B1 (ko) * 2002-07-29 2009-02-06 글락소 그룹 리미티드 라모트리진을 포함하는 서방형 제제

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0459830A1 (fr) * 1990-06-01 1991-12-04 The Wellcome Foundation Limited Composés CNS pharmacologiquement actifs
EP0459829A1 (fr) * 1990-06-01 1991-12-04 The Wellcome Foundation Limited Composés pharmacologiques actifs sur le système nerveux central
WO1993016700A1 (fr) * 1992-02-19 1993-09-02 The Wellcome Foundation Limited Utilisation de 3,5-diamino-6-(2,3-dichlorophenyle)-1,2,4-triazine pour traiter les douleurs et les oedemes
WO1994018972A2 (fr) * 1993-02-25 1994-09-01 Warner-Lambert Company Procedes permettant de traiter des maladies et troubles neurodegeneratifs avec des urees n-(2,6-aromatiques disubstitues)-n'-pyridinyle et d'autres composes anticonvulsivants
WO1997020827A1 (fr) * 1995-12-05 1997-06-12 Laboratorios Del Dr. Esteve, S.A. Derives de fluorophenyl-triazines et pyrimidines comme composes actifs sur le snc

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0459830A1 (fr) * 1990-06-01 1991-12-04 The Wellcome Foundation Limited Composés CNS pharmacologiquement actifs
EP0459829A1 (fr) * 1990-06-01 1991-12-04 The Wellcome Foundation Limited Composés pharmacologiques actifs sur le système nerveux central
WO1993016700A1 (fr) * 1992-02-19 1993-09-02 The Wellcome Foundation Limited Utilisation de 3,5-diamino-6-(2,3-dichlorophenyle)-1,2,4-triazine pour traiter les douleurs et les oedemes
WO1994018972A2 (fr) * 1993-02-25 1994-09-01 Warner-Lambert Company Procedes permettant de traiter des maladies et troubles neurodegeneratifs avec des urees n-(2,6-aromatiques disubstitues)-n'-pyridinyle et d'autres composes anticonvulsivants
WO1997020827A1 (fr) * 1995-12-05 1997-06-12 Laboratorios Del Dr. Esteve, S.A. Derives de fluorophenyl-triazines et pyrimidines comme composes actifs sur le snc

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
D'ANDREA ET AL.: "Effectiveness of lamotrigine in the prophylaxis of migraine with aura. An open pilot study" J. NEUROL. SCI., vol. 150, no. suppl, September 1997, page s239 XP002065865 *
STEINER ET AL.: "Lamotrigine versus placebo in the prophylaxis of migraine with aura" CEPHALALGIA, vol. 17, no. 2, April 1997, pages 109-112, XP002065866 *
STEINER ET AL.: "Safety data from a placebo-controlled trial of lamotrigine" INT. CONGR. SYMP., SER.- R SOC. MED., vol. 214, 1996, pages 31-35, XP002065864 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7709523B2 (en) 2003-01-16 2010-05-04 Newron Pharmaceuticals Spa Alpha-aminoamide derivatives useful as antimigraine agents

Also Published As

Publication number Publication date
CA2274858A1 (fr) 1998-06-18
EP0948325A2 (fr) 1999-10-13
GB9625795D0 (en) 1997-01-29
JP2001510461A (ja) 2001-07-31
WO1998025594A3 (fr) 1998-09-17

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