[go: up one dir, main page]

EP0674518A1 - Application of lamotrigine in the treatment of neurological lesions related to traumatic injuries - Google Patents

Application of lamotrigine in the treatment of neurological lesions related to traumatic injuries

Info

Publication number
EP0674518A1
EP0674518A1 EP94902802A EP94902802A EP0674518A1 EP 0674518 A1 EP0674518 A1 EP 0674518A1 EP 94902802 A EP94902802 A EP 94902802A EP 94902802 A EP94902802 A EP 94902802A EP 0674518 A1 EP0674518 A1 EP 0674518A1
Authority
EP
European Patent Office
Prior art keywords
treatment
lamotrigine
neurological lesions
spinal
preparation
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP94902802A
Other languages
German (de)
French (fr)
Inventor
Adam Doble
Erik Louvel
Jérémy Pratt
Jean-Marie Stutzmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aventis Pharma SA
Original Assignee
Rhone Poulenc Rorer SA
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 Rhone Poulenc Rorer SA filed Critical Rhone Poulenc Rorer SA
Publication of EP0674518A1 publication Critical patent/EP0674518A1/en
Withdrawn legal-status Critical Current

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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • 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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention relates to a new therapeutic application of lamotrigine or the pharmaceutically acceptable salts of this compound.
  • Lamotrigine and the pharmaceutically acceptable salts of this compound are described as anticonvulsants and antiepileptics in particular in patent EP 247892.
  • this compound can also be used in the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or cranio-spinal traumas.
  • lamotrigine decreases the neurological deficit of the animals (paraplegia) linked to the lesion of the spinal cord as well as the histopathological lesions (necrosis of the cord). This reduction is generally equal to or greater than 5%.
  • a) preparation of the animal the rabbits are injected intramuscularly with 5 mg of valium® and 1/16 mg of atropine. 30 minutes later, an isotonic saline infusion is set up and the rabbits are anesthetized by injection 40 mg / kg slow intravenous injection of Nesdonal®. We then put in place a cardioscope because the animal may present, especially during re-injections of Nesdonal®, lasting apnea with bradycardia.
  • PES somesthesic evoked potentials
  • the trauma is carried out by inflating the balloon of a Fogarty French 3 probe placed in the spinal canal in the extradural position. For this, we perform a low lumbar laminectomy. The opening of the yellow ligament allows the passage of the probe up to the level of the first lumbar vertebra and the operating wound is closed. A new PES is recorded to ensure that there is no functional lesion during the passage of the probe. The lesion is then carried out by inflating the balloon with variable amounts of air (0.2; 0.4 and 0.55 ml of air) then the probe is removed. A new PES is performed just after the trauma and is compared (amplitudes and latencies) to the reference PES.
  • the product is injected intraperitoneally once a day for 5 days, at doses between 1 and 8 mg / kg.
  • a spinal cord block is taken comprising the injured level which is placed in 10% formalin. A week later, the cord is extracted from the block (this fixation period seems necessary to avoid post-mortem injury). A hemorrhagic area visible to the naked eye shows the level of trauma. Staged histological sections specify the extent of the lesions.
  • lamotrigine makes it possible to decrease the neurological deficit linked to the lesion of the spinal cord, to protect the sensitive neurological pathways and to decrease the necrotic hemorrhagic zone within the gray substance of the spinal cord. These decreases are generally equal to or greater than 5%.
  • lamotrigine improves the neurological score of animals that have suffered a head trauma and reduces necrotic lesions. This reduction is generally equal to or greater than 5%.
  • salts As pharmaceutically acceptable salts, mention may in particular be made of addition salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate. maleate, methanesulfonate, isethionate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphtoate or substitution derivatives of these derivatives.
  • mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate. maleate, methanesulfonate, isethionate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis- ⁇ -oxynaphtoate or substitution derivatives of these derivatives.
  • the medicaments consist of at least lamotrigine in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutical product. compatible, possibly inert or physiologically active.
  • the medicaments according to the invention can be used orally or parenterally.
  • compositions for oral administration tablets, pills, powders (gelatin capsules, cachets) or granules can be used.
  • the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon.
  • these compositions can also include substances other than thinners, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.
  • compositions for oral administration there can be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing diluents .
  • inert such as water, ethanol, glycerol, vegetable oils or paraffin oil.
  • These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
  • the sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions.
  • solvent or vehicle water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable.
  • These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
  • the doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 800 mg per day by the oral route for an adult with unit doses ranging from 25 to 200 mg of active substance and between 25 and 600 mg per day by the intravenous route for an adult with unit doses ranging from 12.5 to 200 mg of active substance.
  • the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
  • Example A illustrate medicaments according to the invention:
  • Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique:
  • capsules containing 50 mg of active product having the following composition are prepared:
  • a solution for injection containing 10 mg of active product having the following composition is prepared:
  • the invention also relates to the process for the preparation of medicaments useful in the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, consisting in mixing the lamotrigine or the pharmaceutically acceptable salts of this compound. with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
  • the invention also relates to a method of treatment of a mammal and, in particular, of a man presenting with neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, comprising the administration of an effective amount of lamotrigine or the pharmaceutically acceptable salts of this compound.

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Peptides Or Proteins (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Data Exchanges In Wide-Area Networks (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)

Abstract

PCT No. PCT/FR93/01229 Sec. 371 Date May 30, 1995 Sec. 102(e) Date May 30, 1995 PCT Filed Dec. 10, 1993 PCT Pub. No. WO94/13288 PCT Pub. Date Jun. 23, 1994Application of riluzole or its pharmaceutically acceptable salts in the treatment of neurological lesions related to traumatic injuries, especially spinal, cranial or cranial-spinal injuries.

Description

APPLICATION DE LA LAMOTRIGINE APPLICATION OF LAMOTRIGINE
DANS I F TRAITEMENT DE LESIONS NEUROLOGIQUESIN THE TREATMENT OF NEUROLOGICAL LESIONS
LIEES A DES TRAUMATISMESRELATED TO TRAUMA
La présente invention concerne une nouvelle application thérapeutique de la lamotrigine ou les sels pharmaceutiquement acceptables de ce composé.The present invention relates to a new therapeutic application of lamotrigine or the pharmaceutically acceptable salts of this compound.
La lamotrigine et les sels pharmaceutiquement acceptables de ce composé sont décrits comme anticonvulsivants et antiépileptiques notamment dans le brevet EP 247892.Lamotrigine and the pharmaceutically acceptable salts of this compound are described as anticonvulsants and antiepileptics in particular in patent EP 247892.
II a maintenant été trouvé de manière surprenante que ce composé peut aussi être utilisé dans le traitement des lésions neurologiques liées à des traumatismes et, en particulier, à des traumatismes spinaux, crâniens ou crânio-spinaux.It has now surprisingly been found that this compound can also be used in the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or cranio-spinal traumas.
L'activité de ce produit sur les lésions de la moelle épinière a été mise en évidence soit dans le modèle de lésion de moelle chez le rat par la technique de compression ventrale décrite par E. C. BENZEL et coll., Journal of Spinal Disorders, 3, 4, 334-338 (1990), soit dans le modèle de tétraplégie traumatique induite par la compression de la moelle épinière par un microballonnet gonflable selon la technique décrite par D. MARTIN et coll., Journal of Neuroscience Research, 32, 539-550 (1992).The activity of this product on spinal cord injury has been demonstrated either in the model of spinal cord injury in rats by the ventral compression technique described by EC BENZEL et al., Journal of Spinal Disorders, 3, 4, 334-338 (1990), or in the model of traumatic quadriplegia induced by the compression of the spinal cord by an inflatable microballoon according to the technique described by D. MARTIN et al., Journal of Neuroscience Research, 32, 539-550 (1992).
Dans ces tests, la lamotrigine diminue le déficit neurologique des animaux (paraplégie) lié à la lésion de la moelle épinière ainsi que les lésions histopathologiques (nécrose de la moelle). Cette diminution est généralement égale ou supérieure à 5%.In these tests, lamotrigine decreases the neurological deficit of the animals (paraplegia) linked to the lesion of the spinal cord as well as the histopathological lesions (necrosis of the cord). This reduction is generally equal to or greater than 5%.
L'activité de ce produit est également démontrée dans le modèle de lésions médullaires sur 15 lapins "Fauve de Bourgogne" de 4 kg (± 200g). Les lapins sont divisés en trois groupes pour recevoir des traumatismes d'importance variable selon le protocole suivant :The activity of this product is also demonstrated in the model of spinal cord injuries in 15 "Fauve de Bourgogne" rabbits weighing 4 kg (± 200g). Rabbits are divided into three groups to receive trauma of varying importance according to the following protocol:
a) préparation de l'animal : on injecte aux lapins intramusculairement 5 mg de valium® et 1/16 mg d'atropine. 30 minutes après, on met en place une perfusion salée isotonique et anesthésie les lapins par injection intraveineuse lente de 40 mg/kg de Nesdonal®. On met ensuite en place un cardioscope car l'animal peut présenter, surtout lors de réinjections de Nesdonal®, une apnée durable avec bradycardie.a) preparation of the animal: the rabbits are injected intramuscularly with 5 mg of valium® and 1/16 mg of atropine. 30 minutes later, an isotonic saline infusion is set up and the rabbits are anesthetized by injection 40 mg / kg slow intravenous injection of Nesdonal®. We then put in place a cardioscope because the animal may present, especially during re-injections of Nesdonal®, lasting apnea with bradycardia.
b) enregistrement des potentiels évoqués somesthésiques (PES) : ces enregistrements précisent l'intégrité des voies sensitives de la moelle. La stimulation est réalisée au niveau du nerf sciatique poplité interne (SPI). L'intensité de stimulation est calculée pour évoquer un potentiel dans les fibres sensitives de gros calibre, ce qui est réalisé au niveau du seuil de stimulation motrice (mouvement minimal de la patte). Le recueil se fait au moyen d'une électrode plantée dans le scalp au niveau du cortex pariétal controlatéral. Une électrode de référence est placée sur la ligne médiane du scalp au niveau frontal (Fz). Un PES est enregistré avant la pose de la sonde pour servir de référence.b) recording of somesthesic evoked potentials (PES): these records specify the integrity of the sensitive pathways of the cord. The stimulation is performed at the level of the internal popliteal sciatic nerve (SPI). The stimulation intensity is calculated to evoke a potential in large sensory fibers, which is achieved at the level of motor stimulation threshold (minimum movement of the paw). The collection is done by means of an electrode planted in the scalp at the level of the contralateral parietal cortex. A reference electrode is placed on the midline of the scalp at the frontal level (Fz). A PES is recorded before the probe is placed to serve as a reference.
c) réalisation du traumatisme : le traumatisme est réalisé par gonflage du ballonnet d'une sonde de Fogarty French 3 placé dans le canal rachidien en position extradurale. Pour cela, on réalise une laminectomie lombaire basse. L'ouverture du ligament jaune permet le passage de la sonde jusqu'au niveau de la première vertèbre lombaire et la plaie opératoire est refermée. Un nouveau PES est enregistré pour s'assurer de l'absence de lésion fonctionnelle lors du passage de la sonde. La lésion est ensuite réalisée par gonflage du ballonnet avec des quantités variables d'air (0,2; 0,4 et 0,55 ml d'air) puis la sonde est retirée. Un nouveau PES est réalisé juste après le traumatisme et est comparé (amplitudes et latences) au PES de référence.c) realization of the trauma: the trauma is carried out by inflating the balloon of a Fogarty French 3 probe placed in the spinal canal in the extradural position. For this, we perform a low lumbar laminectomy. The opening of the yellow ligament allows the passage of the probe up to the level of the first lumbar vertebra and the operating wound is closed. A new PES is recorded to ensure that there is no functional lesion during the passage of the probe. The lesion is then carried out by inflating the balloon with variable amounts of air (0.2; 0.4 and 0.55 ml of air) then the probe is removed. A new PES is performed just after the trauma and is compared (amplitudes and latencies) to the reference PES.
d) Le produit est injecté par voie intrapéritonéale 1 fois par jour pendant 5 jours, à des doses comprises entre 1 et 8 mg/kg.d) The product is injected intraperitoneally once a day for 5 days, at doses between 1 and 8 mg / kg.
e) histologie : on prélève un bloc rachis-moelle comprenant le niveau lésé qui est mis dans du formol à 10%. Une semaine plus tard, la moelle est extraite du bloc (ce délai de fixation semble nécessaire pour éviter une lésion post-mortem). Une zone hémorragique visible à l'oeil nu montre le niveau du traumatisme. Des coupes histologiques étagées précisent l'extension des lésions. f) résultats : la lamotrigine permet de diminuer le déficit neurologique lié à la lésion de la moelle épinière, de protéger les voies neurologiques sensitives et de diminuer la zone nécrotique hémorragique au sein de la substance grise de la moelle épinière. Ces diminutions sont généralement égales ou supérieures à 5%.e) histology: a spinal cord block is taken comprising the injured level which is placed in 10% formalin. A week later, the cord is extracted from the block (this fixation period seems necessary to avoid post-mortem injury). A hemorrhagic area visible to the naked eye shows the level of trauma. Staged histological sections specify the extent of the lesions. f) results: lamotrigine makes it possible to decrease the neurological deficit linked to the lesion of the spinal cord, to protect the sensitive neurological pathways and to decrease the necrotic hemorrhagic zone within the gray substance of the spinal cord. These decreases are generally equal to or greater than 5%.
L'activité de ce produit dans les traumatismes crâniens a été mise en évidence chez le rat selon la technique décrite par T. K. McINTOSH et coll., Central Nervous System Trauma, 4, 2, 119-134 (1987).The activity of this product in head trauma has been demonstrated in rats according to the technique described by T. K. McINTOSH et al., Central Nervous System Trauma, 4, 2, 119-134 (1987).
Dans ce test, la lamotrigine améliore le score neurologique des animaux ayant subi un traumatisme crânien et réduisent les lésions nécrotiques. Cette diminution est généralement égale ou supérieure à 5%.In this test, lamotrigine improves the neurological score of animals that have suffered a head trauma and reduces necrotic lesions. This reduction is generally equal to or greater than 5%.
Comme sels pharmaceutiquement acceptables peuvent être notamment cités les sels d'addition avec les acides minéraux tels que chlorhydrate, sulfate, nitrate, phosphate ou organiques tels que acétate, propionate, succinate, oxalate, benzoate, fumarate. maléate, méthanesulfonate, iséthionate, théophilline-acétate, salicylate, phénolphtalinate, méthylène-bis-β-oxynaphtoate ou des dérivés de substitution de ces dérivés.As pharmaceutically acceptable salts, mention may in particular be made of addition salts with mineral acids such as hydrochloride, sulfate, nitrate, phosphate or organic salts such as acetate, propionate, succinate, oxalate, benzoate, fumarate. maleate, methanesulfonate, isethionate, theophillin-acetate, salicylate, phenolphthalinate, methylene-bis-β-oxynaphtoate or substitution derivatives of these derivatives.
Les médicaments sont constitués par au moins la lamotrigine sous forme libre ou sous forme d'un sel d'addition avec un acide pharmaceutiquement acceptable, à l'état pur ou sous forme d'une composition dans laquelle il est associé à tout autre produit pharmaceutiquement compatible, pouvant être inerte ou physiologiquement actif. Les médicaments selon l'invention peuvent être employés par voie orale ou parentérale.The medicaments consist of at least lamotrigine in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutical product. compatible, possibly inert or physiologically active. The medicaments according to the invention can be used orally or parenterally.
Comme compositions solides pour administration orale, peuvent être utilisés des comprimés, des pilules, des poudres (capsules de gélatine, cachets) ou des granulés. Dans ces compositions, le principe actif selon l'invention est mélangé à un ou plusieurs diluants inertes, tels que amidon, cellulose, saccharose, lactose ou silice, sous courant d'argon. Ces compositions peuvent également comprendre des substances autres que les diluants, par exemple un ou plusieurs lubrifiants tels que le stéarate de magnésium ou le talc, un colorant, un enrobage (dragées) ou un vernis.As solid compositions for oral administration, tablets, pills, powders (gelatin capsules, cachets) or granules can be used. In these compositions, the active principle according to the invention is mixed with one or more inert diluents, such as starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions can also include substances other than thinners, for example one or more lubricants such as magnesium stearate or talc, a colorant, a coating (dragees) or a varnish.
Comme compositions liquides pour administration orale, on peut utiliser des solutions, des suspensions, des émulsions, des sirops et des élixirs pharmaceutiquement acceptables contenant des diluants., inertes tels que l'eau, l'éthanol, le glycérol, les huiles végétales ou l'huile de paraffine. Ces compositions peuvent comprendre des substances autres que les diluants, par exemple des produits mouillants, édulcorants, épaississants, aromatisants ou stabilisants.As liquid compositions for oral administration, there can be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing diluents . , inert such as water, ethanol, glycerol, vegetable oils or paraffin oil. These compositions can include substances other than diluents, for example wetting, sweetening, thickening, flavoring or stabilizing products.
Les compositions stériles pour administration parentérale, peuvent être de préférence des solutions aqueuses ou non aqueuses, des suspensions ou des émulsions. Comme solvant ou véhicule, on peut employer l'eau, le propylèneglycol, un polyéthylèneglycol, des huiles végétales, en particulier l'huile d'olive, des esters organiques injectables, par exemple l'oléate d'éthyle ou d'autres solvants organiques convenables. Ces compositions peuvent également contenir des adjuvants, en particulier des agents mouillants, isotonisants, émulsifiants, dispersants et stabilisants. La stérilisation peut se faire de plusieurs façons, par exemple par filtration aseptisante, en incorporant à la composition des agents stérilisants, par irra- diation ou par chauffage. Elles peuvent également être préparées sous forme de compositions solides stériles qui peuvent être dissoutes au moment de l'emploi dans de l'eau stérile ou tout autre milieu stérile injectable.The sterile compositions for parenteral administration can preferably be aqueous or non-aqueous solutions, suspensions or emulsions. As solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil, injectable organic esters, for example ethyl oleate or other organic solvents can be used. suitable. These compositions can also contain adjuvants, in particular wetting agents, isotonizers, emulsifiers, dispersants and stabilizers. Sterilization can be done in several ways, for example by aseptic filtration, by incorporating sterilizing agents into the composition, by irradiation or by heating. They can also be prepared in the form of sterile solid compositions which can be dissolved at the time of use in sterile water or any other sterile injectable medium.
Les doses dépendent de l'effet recherché, de la durée du traitement et de la voie d'administration utilisée; elles sont généralement comprises entre 50 et 800 mg par jour par voie orale pour un adulte avec des doses unitaires allant de 25 à 200 mg de substance active et entre 25 et 600 mg par jour par voie intraveineuse pour un adulte avec des doses unitaires allant de 12,5 à 200 mg de substance active.The doses depend on the desired effect, on the duration of the treatment and on the route of administration used; they are generally between 50 and 800 mg per day by the oral route for an adult with unit doses ranging from 25 to 200 mg of active substance and between 25 and 600 mg per day by the intravenous route for an adult with unit doses ranging from 12.5 to 200 mg of active substance.
D'une façon générale, le médecin déterminera la posologie appropriée en fonction de l'âge, du poids et de tous les autres facteurs propres au sujet à traiter.In general, the doctor will determine the appropriate dosage based on age, weight and all other factors specific to the subject to be treated.
Les exemples suivants illustrent des médicaments selon l'invention : Exemple AThe following examples illustrate medicaments according to the invention: Example A
On prépare, selon la technique habituelle, des comprimés dosés à 50 mg de produit actif ayant la composition suivante :Tablets containing 50 mg of active product having the following composition are prepared according to the usual technique:
- Produit actif 50 mg - Mannitol 64 mg- Active product 50 mg - Mannitol 64 mg
- Cellulose microcristalline 50 mg- Microcrystalline cellulose 50 mg
- Polyvidone excipient 12 mg- Polyvidone excipient 12 mg
- Carboxyméthylamidon sodique 16 mg- Carboxymethyl starch sodium 16 mg
- Talc 4 mg - Stéarate de magnésium 2 mg- Talc 4 mg - Magnesium stearate 2 mg
- Silice colloïdale anhydre 2 mg- Anhydrous colloidal silica 2 mg
- Mélange de méthylhydroxypropylcellulose, polyéthylèneglycol 6000, dioxyde de titane (72-3,5-24,5) q.s.p. 1 comprimé pellicule terminé à 245 mg- Mixture of methylhydroxypropylcellulose, polyethylene glycol 6000, titanium dioxide (72-3,5-24,5) q.s.p. 1 film-coated tablet finished at 245 mg
Exemple BExample B
On prépare, selon la technique habituelle, des gélules dosées à 50 mg de produit actif ayant la composition suivante :Using the usual technique, capsules containing 50 mg of active product having the following composition are prepared:
- Produit actif 50 mg- Active product 50 mg
- Cellulose 18 mg - Lactose 55 mg- Cellulose 18 mg - Lactose 55 mg
- Silice colloïdale 1 mg- Colloidal silica 1 mg
- Carboxyméthylamidon sodique 10 mg- Carboxymethyl starch sodium 10 mg
- Talc 10 mg- Talc 10 mg
- Stéarate de magnésium 1 mg- Magnesium stearate 1 mg
Exemple CExample C
On prépare une solution injectable contenant 10 mg de produit actif ayant la composition suivante :A solution for injection containing 10 mg of active product having the following composition is prepared:
- Produit actif 10 mg- Active product 10 mg
- Acide benzoïque 80 mg - Alcool benzylique 0,06 cm3 - Benzoate de sodium 80 mg- Benzoic acid 80 mg - Benzyl alcohol 0.06 cm3 - Sodium benzoate 80 mg
- Ethanol à 95 % 0,4 cm3- 95% ethanol 0.4 cm3
- Hydroxyde de sodium 24 mg- Sodium hydroxide 24 mg
- Propylène glycol 1 ,6 cm3 - Eau q.s.p. 4 cm3- Propylene glycol 1, 6 cm3 - Water q.s.p. 4 cm3
L'invention concerne également le procédé de préparation de médicaments utiles dans le traitement des lésions neurologiques liées à des traumatismes et, en particulier, à des traumatismes spinaux, crâniens ou crânio-spinaux consistant à mélanger la lamotrigine ou les sels pharmaceutiquement acceptables de ce composé avec un ou plusieurs diluants et/ou adjuvants compatibles et pharmaceutiquement acceptables.The invention also relates to the process for the preparation of medicaments useful in the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, consisting in mixing the lamotrigine or the pharmaceutically acceptable salts of this compound. with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
L'invention concerne également une méthode de traitement d'un mammifère et, notamment, de l'homme présentant des lésions neurologiques liées à des traumatismes et, en particulier, à des traumatismes spinaux, crâniens ou crânio-spinaux comprenant l'administration d'une quantité efficace de la lamotrigine ou les sels pharmaceutiquement acceptables de ce composé. The invention also relates to a method of treatment of a mammal and, in particular, of a man presenting with neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, comprising the administration of an effective amount of lamotrigine or the pharmaceutically acceptable salts of this compound.

Claims

REVENDICATIONS
1 - Application de la lamotrigine ou les sels pharmaceutiquement acceptables de ce composé à la préparation de médicaments destinés au traitement des lésions neurologiques liées à des traumatismes.1 - Application of lamotrigine or the pharmaceutically acceptable salts of this compound to the preparation of medicaments intended for the treatment of neurological lesions linked to traumas.
2 - Application selon la revendication 1 à la préparation de médicaments destinés au traitement des lésions neurologiques liées aux traumatismes spinaux.2 - Application according to claim 1 for the preparation of medicaments intended for the treatment of neurological lesions linked to spinal trauma.
3 - Application selon la revendication 1 à la préparation de médicaments destinés au traitement des lésions neurologiques liées aux traumatismes crâniens.3 - Application according to claim 1 for the preparation of medicaments intended for the treatment of neurological lesions linked to head trauma.
4 - Application selon la revendication 1 à la préparation de médicaments destinés au traitement des lésions neurologiques liées aux traumatismes crânio-spinaux.4 - Application according to claim 1 for the preparation of medicaments intended for the treatment of neurological lesions linked to cranio-spinal trauma.
5 - Application selon l'une des revendications 1 à 4 pour obtenir un médicament utile par voie orale comprenant 25 à 200 mg de lamotrigine.5 - Application according to one of claims 1 to 4 to obtain a useful oral medication comprising 25 to 200 mg of lamotrigine.
6 - Application selon l'une des revendications 1 à 4 pour obtenir un médicament utile par voie intraveineuse comprenant 12,5 à 200 mg de lamotrigine .6 - Application according to one of claims 1 to 4 to obtain a drug useful intravenously comprising 12.5 to 200 mg of lamotrigine.
7 - Procédé de préparation d'un médicament utile pour le traitement des lésions neurologiques liées à des traumatismes et, en particulier, à des traumatismes spinaux, crâniens ou crânio-spinaux caractérisé en ce que l'on mélange la lamotrigine ou les sels pharmaceutiquement acceptables de ce composé avec un ou plusieurs diluants et/ou adjuvants compatibles et pharaceutiquement acceptables. 7 - Process for the preparation of a medicament useful for the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, characterized in that the lamotrigine or the pharmaceutically acceptable salts are mixed of this compound with one or more compatible and pharmacologically acceptable diluents and / or adjuvants.
EP94902802A 1992-12-16 1993-12-10 Application of lamotrigine in the treatment of neurological lesions related to traumatic injuries Withdrawn EP0674518A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9215148 1992-12-16
FR9215148A FR2699077B1 (en) 1992-12-16 1992-12-16 Application of anticonvulsants in the treatment of neurological lesions linked to trauma.
PCT/FR1993/001227 WO1994013296A1 (en) 1992-12-16 1993-12-10 Application of lamotrigine in the treatment of neurological lesions related to traumatic injuries

Publications (1)

Publication Number Publication Date
EP0674518A1 true EP0674518A1 (en) 1995-10-04

Family

ID=9436652

Family Applications (3)

Application Number Title Priority Date Filing Date
EP94902019A Expired - Lifetime EP0674512B1 (en) 1992-12-16 1993-12-10 Application of riluzole in the treatment of neurological lesions related to traumatic injuries
EP94902802A Withdrawn EP0674518A1 (en) 1992-12-16 1993-12-10 Application of lamotrigine in the treatment of neurological lesions related to traumatic injuries
EP94902018A Ceased EP0674520A1 (en) 1992-12-16 1993-12-10 Application of carbamazepine and oxcarbazepine in the treatment of neurological lesions related to traumatic injuries

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP94902019A Expired - Lifetime EP0674512B1 (en) 1992-12-16 1993-12-10 Application of riluzole in the treatment of neurological lesions related to traumatic injuries

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP94902018A Ceased EP0674520A1 (en) 1992-12-16 1993-12-10 Application of carbamazepine and oxcarbazepine in the treatment of neurological lesions related to traumatic injuries

Country Status (23)

Country Link
US (1) US5830907A (en)
EP (3) EP0674512B1 (en)
JP (3) JPH08504428A (en)
KR (3) KR100298808B1 (en)
AT (1) ATE164067T1 (en)
AU (3) AU5653994A (en)
CA (3) CA2151604C (en)
CZ (3) CZ154695A3 (en)
DE (1) DE69317578T2 (en)
DK (1) DK0674512T3 (en)
ES (1) ES2113635T3 (en)
FR (1) FR2699077B1 (en)
GR (1) GR3026403T3 (en)
HU (3) HUT71812A (en)
IL (3) IL108051A (en)
MX (3) MX9307884A (en)
NO (3) NO307027B1 (en)
PL (3) PL309347A1 (en)
RU (1) RU2142800C1 (en)
SK (3) SK78595A3 (en)
UA (1) UA41906C2 (en)
WO (3) WO1994013298A1 (en)
ZA (3) ZA939399B (en)

Families Citing this family (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2700117B1 (en) * 1993-01-07 1995-02-03 Rhone Poulenc Rorer Sa Application of anti-convulsants in the treatment of Parkinson's disease and parkinsonian syndromes.
GB9424766D0 (en) * 1994-12-07 1995-02-08 Wellcome Found Pharmaceutical composition
FR2733684B1 (en) 1995-05-03 1997-05-30 Cird Galderma USE OF RETINOIDS IN A COSMETIC COMPOSITION OR FOR THE MANUFACTURE OF A PHARMACEUTICAL COMPOSITION
GB9512854D0 (en) * 1995-06-23 1995-08-23 Wellcome Found Novel formulation
CO4920215A1 (en) * 1997-02-14 2000-05-29 Novartis Ag OXACARBAZEPINE TABLETS COATED WITH A FILM AND METHOD FOR THE PRODUCTION OF THESE FORMULATIONS
US20020022056A1 (en) 1997-02-14 2002-02-21 Burkhard Schlutermann Oxacarbazepine film-coated tablets
ES2231757T3 (en) 1997-09-05 2005-05-16 Glaxo Group Limited PHARMACEUTICAL COMPOSITIONS THAT INCLUDE DERIVATIVES OF 2,3-DIARIL-PIRAZOLO (1,5-B) PIRIDAZINE.
GB9808015D0 (en) * 1998-04-15 1998-06-17 United Medical And Dental Scho Protection of the nervous system from the effects of inflammatory disease
US6150423A (en) * 1998-10-15 2000-11-21 Phoenix Scientific, Inc. Propofol-based anesthetic and method of making same
FR2787028B1 (en) * 1998-12-15 2002-10-18 Aventis Pharma Sa USE OF RILUZOLE IN THE TREATMENT OF ACOUSTIC TRAUMA
EP1173175A1 (en) * 1999-04-29 2002-01-23 Centre National De La Recherche Scientifique (Cnrs) A method for the prevention of ischemic spinal cord injury caused by aortic crossclamping
GB9925962D0 (en) * 1999-11-02 1999-12-29 Novartis Ag Organic compounds
GB9930058D0 (en) * 1999-12-20 2000-02-09 Novartis Ag Organic compounds
US20060252745A1 (en) 2005-05-06 2006-11-09 Almeida Jose L D Methods of preparing pharmaceutical compositions comprising eslicarbazepine acetate and methods of use
WO2007022568A1 (en) 2005-08-25 2007-03-01 Steven Michael Weiss Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption in coronary blood flow
GB0700773D0 (en) 2007-01-15 2007-02-21 Portela & Ca Sa Drug therapies
US9303038B2 (en) 2011-09-06 2016-04-05 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy and neurological diseases
WO2013168021A1 (en) 2012-05-07 2013-11-14 Mahesh Kandula Compositions and methods for treatment of neuromuscular disorders and neurodegenerative disorders
US9399634B2 (en) 2012-05-07 2016-07-26 Cellix Bio Private Limited Compositions and methods for the treatment of depression
EP2847169A4 (en) 2012-05-07 2015-09-30 Cellix Bio Private Ltd Compositions and methods for the treatment of neurological disorders
US9403826B2 (en) 2012-05-08 2016-08-02 Cellix Bio Private Limited Compositions and methods for the treatment of inflammatory disorders
WO2013167993A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of neurological degenerative disorders
WO2013168023A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for treatment of parkinson's disease
US9522884B2 (en) 2012-05-08 2016-12-20 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic disorders
WO2013168025A1 (en) 2012-05-08 2013-11-14 Mahesh Kandula Compositions and methods for treatment of blood clotting disorders
WO2013168004A2 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of fibromyalgia pain
WO2013167999A2 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of neurologic diseases
US9315478B2 (en) 2012-05-10 2016-04-19 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
WO2013168005A2 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of restless leg syndrome and fibromyalgia
WO2013168001A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of moderate to severe pain
WO2013168011A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of chronic pain
WO2013168016A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of metabolic syndrome
US9499526B2 (en) 2012-05-10 2016-11-22 Cellix Bio Private Limited Compositions and methods for the treatment of neurologic diseases
US9499527B2 (en) 2012-05-10 2016-11-22 Cellix Bio Private Limited Compositions and methods for the treatment of familial amyloid polyneuropathy
US9242939B2 (en) 2012-05-10 2016-01-26 Cellix Bio Private Limited Compositions and methods for the treatment of respiratory disorders
WO2013168000A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of severe pain
US9394288B2 (en) 2012-05-10 2016-07-19 Cellix Bio Private Limited Compositions and methods for the treatment of asthma and allergy
WO2013168002A1 (en) 2012-05-10 2013-11-14 Mahesh Kandula Compositions and methods for the treatment of neurological conditions
CA2873104A1 (en) 2012-05-23 2013-11-28 Cellixbio Private Limited Compositions and methods for the treatment of mucositis
WO2013175376A2 (en) 2012-05-23 2013-11-28 Mahesh Kandula Compositions and methods for the treatment of local pain
EP2852569B1 (en) 2012-05-23 2020-10-14 Cellixbio Private Limited Compositions and methods for the treatment of multiple sclerosis
EP2852570B1 (en) 2012-05-23 2020-04-22 Cellixbio Private Limited Composition for the treatment of inflammatory bowel disease
US9434729B2 (en) 2012-05-23 2016-09-06 Cellix Bio Private Limited Compositions and methods for the treatment of periodontitis and rheumatoid arthritis
US9227974B2 (en) 2012-05-23 2016-01-05 Cellex Bio Private Limited Compositions and methods for the treatment of respiratory disorders
US9108942B1 (en) 2014-11-05 2015-08-18 Mahesh Kandula Compositions and methods for the treatment of moderate to severe pain
WO2014020480A2 (en) 2012-08-03 2014-02-06 Mahesh Kandula Compositions and methods for the treatment migraine and neurologic diseases
WO2014037833A2 (en) 2012-09-06 2014-03-13 Mahesh Kandula Compositions and methods for the treatment inflammation and lipid disorders
SG11201407325YA (en) 2012-09-08 2014-12-30 Cellix Bio Private Ltd Compositions and methods for treatment of inflammation and lipid disorders
US9333187B1 (en) 2013-05-15 2016-05-10 Cellix Bio Private Limited Compositions and methods for the treatment of inflammatory bowel disease
WO2014195961A1 (en) 2013-06-04 2014-12-11 Mahesh Kandula Compositions and methods for the treatment of diabetes and pre-diabetes
US9096537B1 (en) 2014-12-31 2015-08-04 Mahesh Kandula Compositions and methods for the treatment of mucositis
WO2016046835A1 (en) 2014-09-26 2016-03-31 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy and neurological disorders
CN107207403A (en) 2014-09-29 2017-09-26 塞尔利克斯生物私人有限公司 Composition and method for treating multiple sclerosis
AU2014414316B2 (en) 2014-10-27 2020-04-09 Cellix Bio Private Limited Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis
US9173877B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
US9150557B1 (en) 2014-11-05 2015-10-06 Cellix Bio Private Limited Compositions and methods for the treatment of hyperglycemia
US9284287B1 (en) 2014-11-05 2016-03-15 Cellix Bio Private Limited Compositions and methods for the suppression of carbonic anhydrase activity
US9175008B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Prodrugs of anti-platelet agents
US9290486B1 (en) 2014-11-05 2016-03-22 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy
US9321716B1 (en) 2014-11-05 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
US10208014B2 (en) 2014-11-05 2019-02-19 Cellix Bio Private Limited Compositions and methods for the treatment of neurological disorders
US9932294B2 (en) 2014-12-01 2018-04-03 Cellix Bio Private Limited Compositions and methods for the treatment of multiple sclerosis
US9206111B1 (en) 2014-12-17 2015-12-08 Cellix Bio Private Limited Compositions and methods for the treatment of neurological diseases
JP6679616B2 (en) 2015-01-06 2020-04-22 セリックス バイオ プライヴェート リミテッドＣｅｌｌｉｘ Ｂｉｏ Ｐｒｉｖａｔｅ Ｌｉｍｉｔｅｄ Compositions and methods for the treatment of inflammation and pain
EP4119539A1 (en) 2015-09-23 2023-01-18 XWPharma Ltd. Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof
EP3601235A4 (en) 2017-03-30 2020-11-18 XW Laboratories Inc. Bicyclic heteroaryl derivatives and preparation and uses thereof
US10322114B2 (en) 2017-07-31 2019-06-18 Above And Beyond Nb, Llc Formulation of a riluzole solution with beta-cyclodextrins
US20200289476A1 (en) * 2017-11-28 2020-09-17 University Of Houston System Liquid formulations of riluzole for oral and intravenous use
CN114042070A (en) 2018-09-30 2022-02-15 凯瑞康宁生物工程（武汉）有限公司 Compounds as neuronal histamine receptor-3 antagonists and uses thereof
TW202136194A (en) 2019-12-20 2021-10-01 香港商凱瑞康寧有限公司 Methods of synthesizing 4-valyloxybutyric acid
KR20230008190A (en) 2020-06-18 2023-01-13 엑스더블유파마 리미티드 Pharmaceutical granulating agent for water-soluble drug substances
AU2021292406B2 (en) 2020-06-18 2024-03-14 XWPharma Ltd. Controlled release granulations of water-soluble active pharmaceutical ingredients
US11896573B2 (en) 2020-07-24 2024-02-13 XWPharma Ltd. Pharmaceutical compositions and pharmacokinetics of a gamma-hydroxybutyric acid derivative
WO2022076466A1 (en) 2020-10-05 2022-04-14 XWPharma Ltd. Modified release compositions of a gamma-hydroxybutyric acid derivative
EP4308086A1 (en) 2021-03-19 2024-01-24 XWPharma Ltd. Pharmacokinetics of combined release formulations of a gamma-hydroxybutyric acid derivative

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK153787C (en) * 1979-06-01 1989-01-16 Wellcome Found METHOD OF ANALOGUE FOR THE PREPARATION OF SUBSTITUTED 3,5-DIAMINO-6-PHENYL-1,2,4-TRIAZINES AND ALFA-CYANOBENZYLIDEEN-AMINOGUANIDE COMPOUNDS FOR USE AS INTERMEDIATES
FR2492258A1 (en) * 1980-10-17 1982-04-23 Pharmindustrie NEW AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE-BASED MEDICINAL PRODUCT
US4431641A (en) * 1980-10-17 1984-02-14 Ciba-Geigy Corporation Pharmaceutical compositions having antiepileptic and antineuralgic action
GB8613183D0 (en) * 1986-05-30 1986-07-02 Wellcome Found Triazine salt
US4826860A (en) * 1987-03-16 1989-05-02 Warner-Lambert Company Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents
US4918090A (en) * 1988-01-25 1990-04-17 Warner-Lambert Company Substituted 2-aminbenzothiazoles and derivatives useful as cerebrovascular agents
US5240948A (en) * 1989-12-13 1993-08-31 Rhone-Poulenc Rorer Pharmaceuticals Inc. 3-(3-alkylthiopropyl)benzothiazoline derivatives, their preparation and the medicament containing them
GB9012312D0 (en) * 1990-06-01 1990-07-18 Wellcome Found Pharmacologically active cns compounds
PT100115B (en) * 1991-02-08 1999-06-30 Cambridge Neuroscience Inc SUBSTITUTED GUANIDINES AND ITS UTILITY DERIVATIVES AS NEUROTRANSMITOR RELEASE MODULATORS AND TRACEABILITY ASSAYS FOR NEUROTRANSMITTER RELEASE BLOCKERS
FR2688138B1 (en) * 1992-03-06 1995-05-05 Rhone Poulenc Rorer Sa APPLICATION OF AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE TO OBTAIN A MEDICINE FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9413296A1 *

Also Published As

Publication number Publication date
PL309348A1 (en) 1995-10-02
KR100298808B1 (en) 2001-11-22
SK78795A3 (en) 1996-05-08
PL309347A1 (en) 1995-10-02
JPH08504430A (en) 1996-05-14
KR950703954A (en) 1995-11-17
NO307027B1 (en) 2000-01-31
NO952230L (en) 1995-06-06
SK78695A3 (en) 1996-05-08
AU5653994A (en) 1994-07-04
MX9307883A (en) 1994-06-30
IL108051A0 (en) 1994-04-12
NO952228L (en) 1995-06-06
ZA939400B (en) 1994-08-19
NO952228D0 (en) 1995-06-06
JPH08504429A (en) 1996-05-14
AU678795B2 (en) 1997-06-12
NO952230D0 (en) 1995-06-06
NO952229L (en) 1995-06-06
JP3712239B2 (en) 2005-11-02
CA2151601A1 (en) 1994-06-23
GR3026403T3 (en) 1998-06-30
EP0674520A1 (en) 1995-10-04
CZ154795A3 (en) 1995-11-15
HUT71812A (en) 1996-02-28
PL309346A1 (en) 1995-10-02
MX9307882A (en) 1994-06-30
DK0674512T3 (en) 1998-05-25
AU5654094A (en) 1994-07-04
DE69317578D1 (en) 1998-04-23
SK279759B6 (en) 1999-03-12
CZ284420B6 (en) 1998-11-11
US5830907A (en) 1998-11-03
CA2151604A1 (en) 1994-06-23
HU9501752D0 (en) 1995-08-28
WO1994013296A1 (en) 1994-06-23
RU2142800C1 (en) 1999-12-20
KR950703965A (en) 1995-11-17
CA2151604C (en) 2005-09-20
IL108052A0 (en) 1994-04-12
NO952229D0 (en) 1995-06-06
WO1994013298A1 (en) 1994-06-23
FR2699077A1 (en) 1994-06-17
HU9501753D0 (en) 1995-08-28
CZ154595A3 (en) 1995-11-15
KR950703968A (en) 1995-11-17
EP0674512B1 (en) 1998-03-18
MX9307884A (en) 1994-06-30
IL108051A (en) 1999-05-09
CZ154695A3 (en) 1995-11-15
FR2699077B1 (en) 1995-01-13
AU5702094A (en) 1994-07-04
HU9501751D0 (en) 1995-08-28
WO1994013288A1 (en) 1994-06-23
HUT71839A (en) 1996-02-28
HU217133B (en) 1999-11-29
IL108053A0 (en) 1994-04-12
JPH08504428A (en) 1996-05-14
CA2151603A1 (en) 1994-06-23
UA41906C2 (en) 2001-10-15
SK78595A3 (en) 1996-05-08
EP0674512A1 (en) 1995-10-04
ZA939399B (en) 1994-08-22
DE69317578T2 (en) 1998-07-23
HUT71814A (en) 1996-02-28
ES2113635T3 (en) 1998-05-01
ZA939401B (en) 1994-08-19
ATE164067T1 (en) 1998-04-15

Similar Documents

Publication Publication Date Title
CA2151604C (en) Application of riluzole in the treatment of neurological lesions associated with traumas
EP0678023B1 (en) Application of riluzole in the treatment of parkinson's disease and parkinsonian syndromes
WO1994020103A1 (en) Use of riluzole for treating aids-related neural disorders
DE69906969T2 (en) USE OF ARYL (OR HETEROARYL) AZOLYLCARBINOL DERIVATIVES IN THE PRODUCTION OF MEDICATIONS FOR TREATING NEUROGEN INFLAMMATION
FR2619713A1 (en) APPLICATION OF AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE TO OBTAIN MEDICINE FOR THE TREATMENT OF SLEEP AND DEPRESSION DISORDERS
FR2699078A1 (en) Use of riluzole to treat neurological lesions
FR2699079A1 (en) Use of riluzole to treat neurological lesions
EP1052989B1 (en) Use of 2-amino-6- trifluoromehthoxy- benzothiazole for preventing or treating cerebellum dysfunction
EP0678022B1 (en) Application of riluzole as a radiorestorer
DE60118924T2 (en) USE OF THE RILUZOL OR ITS SALTS FOR PHOPHYLAXIS AND TREATMENT OF ADRENOLEUKODYSTROPHY
FR2700114A1 (en) Use of the anticonvulsant lamotrigin and its salts
EP0374042A2 (en) Use of carbipramine in the preparation of a medicament for the treatment of anxiety and sleeping disorders
NL7908286A (en) PREPARATION FOR TREATING PHYSIOLOGICAL DISORDERS IN MAMMALIA SPECIES CHARACTERIZED BY ABERRANT HIGH-FREQUENCY DISCHARGE OF NERVE FIBERS.
FR2700115A1 (en) Use of anticonvulsants carbamazepine and oxcarbazepine
EP0863756A1 (en) Use of 2-iminobenzothiazolines for treating parkinson's disease and parkinsonian syndromes

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19950602

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT SE

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19970701