EP0674520A1 - Verwendung von carbamazepin und oxcarbazepin zur behandlung von traumatischen neurologischen schädungen - Google Patents

Verwendung von carbamazepin und oxcarbazepin zur behandlung von traumatischen neurologischen schädungen

Info

Publication number: EP0674520A1
Authority: EP; European Patent Office
Prior art keywords: treatment; oxcarbazepine; carbamazepine; neurological lesions; spinal
Prior art date: 1992-12-16
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.): Ceased

Application number

EP94902018A

Other languages

English (en)

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.)

1992-12-16

Filing date

1993-12-10

Publication date

1995-10-04

1993-12-10 Application filed by Rhone Poulenc Rorer SA filed Critical Rhone Poulenc Rorer SA

1995-10-04 Publication of EP0674520A1 publication Critical patent/EP0674520A1/de

Status Ceased legal-status Critical Current

Links

208000014674 injury Diseases 0.000 title claims abstract description 20
230000003902 lesion Effects 0.000 title claims abstract description 19
230000000926 neurological effect Effects 0.000 title claims abstract description 13
229960000623 carbamazepine Drugs 0.000 title claims description 12
FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 title claims description 12
229960001816 oxcarbazepine Drugs 0.000 title claims description 12
CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 title claims description 12
230000008736 traumatic injury Effects 0.000 title abstract 2
150000003839 salts Chemical class 0.000 claims abstract description 11
230000008733 trauma Effects 0.000 claims description 17
239000001961 anticonvulsive agent Substances 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
229960003965 antiepileptics Drugs 0.000 claims description 8
238000000034 method Methods 0.000 claims description 8
230000001773 anti-convulsant effect Effects 0.000 claims description 7
150000001875 compounds Chemical class 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 7
206010019196 Head injury Diseases 0.000 claims description 3
239000002671 adjuvant Substances 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
230000008569 process Effects 0.000 claims description 2
229940079593 drug Drugs 0.000 claims 1
229940126701 oral medication Drugs 0.000 claims 1
FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 abstract 1
208000020339 Spinal injury Diseases 0.000 abstract 1
229960004181 riluzole Drugs 0.000 abstract 1
239000000203 mixture Substances 0.000 description 12
210000000278 spinal cord Anatomy 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
239000000523 sample Substances 0.000 description 5
241001465754 Metazoa Species 0.000 description 4
241000283973 Oryctolagus cuniculus Species 0.000 description 4
230000000694 effects Effects 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
230000007423 decrease Effects 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
239000002253 acid Substances 0.000 description 2
239000013543 active substance Substances 0.000 description 2
229940125681 anticonvulsant agent Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000008119 colloidal silica Substances 0.000 description 2
230000006835 compression Effects 0.000 description 2
238000007906 compression Methods 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
230000002008 hemorrhagic effect Effects 0.000 description 2
WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
239000003701 inert diluent Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
230000007971 neurological deficit Effects 0.000 description 2
230000037361 pathway Effects 0.000 description 2
230000009467 reduction Effects 0.000 description 2
210000004761 scalp Anatomy 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
-1 theophillin- acetate Chemical compound 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
229930003347 Atropine Natural products 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
208000001738 Nervous System Trauma Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
206010033892 Paraplegia Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010037714 Quadriplegia Diseases 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
208000020307 Spinal disease Diseases 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
230000003556 anti-epileptic effect Effects 0.000 description 1
208000008784 apnea Diseases 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
229960000396 atropine Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
230000036471 bradycardia Effects 0.000 description 1
208000006218 bradycardia Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000006378 damage Effects 0.000 description 1
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
239000000835 fiber Substances 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
238000002684 laminectomy Methods 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
210000003041 ligament Anatomy 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
230000001338 necrotic effect Effects 0.000 description 1
208000013435 necrotic lesion Diseases 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001936 parietal effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
210000003497 sciatic nerve Anatomy 0.000 description 1
230000001953 sensory effect Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000008719 thickening Effects 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
229940072690 valium Drugs 0.000 description 1
239000002966 varnish Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

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 application
Carbamazepine and oxcarbazepine or the pharmaceutically acceptable salts of these compounds are described as anticonvulsants and antiepileptics in particular in patent EP 50589.
these compounds can also be used in the treatment of neurological lesions linked to traumas and, in particular, to spinal, cranial or cranio-spinal traumas.
carbamazepine and oxcarbazepine decrease 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). 5 This reduction is generally equal to or greater than 5%.
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 products are injected intraperitoneally once a day for 5 days, at doses between 1 and 8 mg / kg.
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.
carbamazepine and oxcarbazepine make it possible to reduce 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%.
carbamazepine and oxcarbazepine improve the neurological score of animals that have suffered a head injury and reduce necrotic lesions. This reduction is generally equal to or greater than 5%.
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- ⁇ -oxynaphthoate 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- ⁇ -oxynaphthoate or substitution derivatives of these derivatives.
the medicaments consist of at least one anticonvulsant chosen from carbamazepine and oxcarbazepine 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 pharmaceutically compatible product, which may be 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 may be used pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs containing inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
inert diluents such as water, ethanol, glycerol, vegetable oils or oil paraffin.
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 an anticonvulsant chosen from carbamazepine and oxcarbazepine or the pharmaceutically acceptable salts of these compounds with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
an anticonvulsant chosen from carbamazepine and oxcarbazepine or the pharmaceutically acceptable salts of these compounds with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants.
the invention also relates to a method of treating a mammal and, in particular a man, presenting neurological lesions linked to traumas and, in particular, to spinal, cranial or craniospinal traumas, comprising the administration of a effective amount of an anticonvulsant selected from carbamazepine and oxcarbazepine or the pharmaceutically acceptable salts of this compound.

Landscapes

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

EP94902018A 1992-12-16 1993-12-10 Verwendung von carbamazepin und oxcarbazepin zur behandlung von traumatischen neurologischen schädungen Ceased EP0674520A1 (de)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9215148A FR2699077B1 (fr)	1992-12-16	1992-12-16	Application d'anticonvulsivants dans le traitement de lésions neurologiques liées à des traumatismes.
FR9215148		1992-12-16
PCT/FR1993/001228 WO1994013298A1 (fr)	1992-12-16	1993-12-10	Application de la carbamazepine et de l'oxcarbazepine dans le traitement de lesions neurologiques liees a des traumatismes

Publications (1)

Publication Number	Publication Date
EP0674520A1 true EP0674520A1 (de)	1995-10-04

Family

ID=9436652

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
EP94902019A Expired - Lifetime EP0674512B1 (de)	1992-12-16	1993-12-10	Verwendung von riluzole zur behandlung von traumatischen neurologischen-schädigungen
EP94902018A Ceased EP0674520A1 (de)	1992-12-16	1993-12-10	Verwendung von carbamazepin und oxcarbazepin zur behandlung von traumatischen neurologischen schädungen
EP94902802A Withdrawn EP0674518A1 (de)	1992-12-16	1993-12-10	Verwendung von lamotrigin zur behandlung von traumatischen neurologischen schädungen

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
EP94902019A Expired - Lifetime EP0674512B1 (de)	1992-12-16	1993-12-10	Verwendung von riluzole zur behandlung von traumatischen neurologischen-schädigungen

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
EP94902802A Withdrawn EP0674518A1 (de)	1992-12-16	1993-12-10	Verwendung von lamotrigin zur behandlung von traumatischen neurologischen schädungen

Country Status (23)

Country	Link
US (1)	US5830907A (de)
EP (3)	EP0674512B1 (de)
JP (3)	JPH08504428A (de)
KR (3)	KR100298808B1 (de)
AT (1)	ATE164067T1 (de)
AU (3)	AU678795B2 (de)
CA (3)	CA2151603A1 (de)
CZ (3)	CZ154695A3 (de)
DE (1)	DE69317578T2 (de)
DK (1)	DK0674512T3 (de)
ES (1)	ES2113635T3 (de)
FR (1)	FR2699077B1 (de)
GR (1)	GR3026403T3 (de)
HU (3)	HU217133B (de)
IL (3)	IL108052A0 (de)
MX (3)	MX9307884A (de)
NO (3)	NO307027B1 (de)
PL (3)	PL309346A1 (de)
RU (1)	RU2142800C1 (de)
SK (3)	SK78795A3 (de)
UA (1)	UA41906C2 (de)
WO (3)	WO1994013296A1 (de)
ZA (3)	ZA939400B (de)

Families Citing this family (78)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2700117B1 (fr) *	1993-01-07	1995-02-03	Rhone Poulenc Rorer Sa	Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens.
GB9424766D0 (en) *	1994-12-07	1995-02-08	Wellcome Found	Pharmaceutical composition
FR2733684B1 (fr)	1995-05-03	1997-05-30	Cird Galderma	Utilisation de retinoides dans une composition cosmetique ou pour la fabrication d'une composition pharmaceutique
GB9512854D0 (en) *	1995-06-23	1995-08-23	Wellcome Found	Novel formulation
CO4920215A1 (es) *	1997-02-14	2000-05-29	Novartis Ag	Tabletas de oxacarbazepina recubiertas de una pelicula y metodo para la produccion de estas formulaciones
US20020022056A1 (en)	1997-02-14	2002-02-21	Burkhard Schlutermann	Oxacarbazepine film-coated tablets
ATE281458T1 (de)	1997-09-05	2004-11-15	Glaxo Group Ltd	Pharmazeutische zusammensetzung, enthaltend 2,3- diaryl-pyrazolo(1,5-b)pyridazin derivate
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 (fr) *	1998-12-15	2002-10-18	Aventis Pharma Sa	Utilisation du riluzole dans le traitement des traumatismes acoustiques
US6239156B1 (en) *	1999-04-29	2001-05-29	Centre National De La Recherche Scientifique Cnrs	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
RU2240113C1 (ru) *	2003-01-23	2004-11-20	Государственное образовательное учреждение высшего профессионального образования Московская медицинская академия им. И.М.Сеченова	Способ экстренной медикаментозной помощи при острой травме спинного мозга
US20060252745A1 (en)	2005-05-06	2006-11-09	Almeida Jose L D	Methods of preparing pharmaceutical compositions comprising eslicarbazepine acetate and methods of use
EP1924326B1 (de)	2005-08-25	2016-10-12	Steven Michael Weiss	Reduzierung von myokard-schaden und inzidenz von arrhythmien durch verlust, verringerung oder unterbrechung des koronaren blutflusses
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
JP2015522531A (ja)	2012-05-07	2015-08-06	セリックスビオプライヴェートリミテッド	神経筋疾患及び神経変性疾患の治療のための組成物及び方法
WO2013167990A1 (en)	2012-05-07	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of depression
US9738631B2 (en)	2012-05-07	2017-08-22	Cellix Bio Private Limited	Compositions and methods for the treatment of neurological disorders
US9309233B2 (en)	2012-05-08	2016-04-12	Cellix Bio Private Limited	Compositions and methods for the treatment of blood clotting disorders
US9403826B2 (en)	2012-05-08	2016-08-02	Cellix Bio Private Limited	Compositions and methods for the treatment of inflammatory disorders
US9266823B2 (en)	2012-05-08	2016-02-23	Cellix Bio Private Limited	Compositions and methods for the 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
US9434704B2 (en)	2012-05-08	2016-09-06	Cellix Bio Private Limited	Compositions and methods for the treatment of neurological degenerative disorders
WO2013168002A1 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of neurological conditions
WO2013168011A1 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of chronic pain
US9315461B2 (en)	2012-05-10	2016-04-19	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
US9321775B2 (en)	2012-05-10	2016-04-26	Cellix Bio Private Limited	Compositions and methods for the treatment of moderate to severe pain
SG11201407318UA (en)	2012-05-10	2014-12-30	Cellix Bio Private Ltd	Compositions and methods for the treatment of metabolic syndrome
US9242939B2 (en)	2012-05-10	2016-01-26	Cellix Bio Private Limited	Compositions and methods for the treatment of respiratory disorders
WO2013167997A2 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of metabolic syndrome
WO2013168000A1 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of severe pain
WO2013168004A2 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of fibromyalgia pain
US9339484B2 (en)	2012-05-10	2016-05-17	Cellix Bio Private Limited	Compositions and methods for the treatment of restless leg syndrome and fibromyalgia
WO2013168015A1 (en)	2012-05-10	2013-11-14	Mahesh Kandula	Compositions and methods for the treatment of asthma and allergy
US9499526B2 (en)	2012-05-10	2016-11-22	Cellix Bio Private Limited	Compositions and methods for the treatment of neurologic diseases
WO2013175347A2 (en)	2012-05-23	2013-11-28	Mahesh Kandula	Compositions and methods for the treatment of respiratory disorders
WO2013175376A2 (en)	2012-05-23	2013-11-28	Mahesh Kandula	Compositions and methods for the treatment of local pain
WO2013175344A2 (en)	2012-05-23	2013-11-28	Mahesh Kandula	Compositions and methods for the treatment of periodontitis and rheumatoid arthritis
US9498461B2 (en)	2012-05-23	2016-11-22	Cellix Bio Private Limited	Compositions and methods for the treatment of inflammatory bowel disease
AU2013264820A1 (en)	2012-05-23	2014-11-27	Cellixbio Private Limited	Compositions and methods for treatment of mucositis
AU2013264896A1 (en)	2012-05-23	2014-11-27	Cellixbio Private Limited	Compositions and methods for the treatment of multiple sclerosis
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
US9624168B2 (en)	2012-09-06	2017-04-18	Cellix Bio Private Limited	Compositions and methods for the treatment inflammation and lipid disorders
CA2873029A1 (en)	2012-09-08	2014-03-13	Cellixbio Private Limited	Compositions and methods for the 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
SG11201509782TA (en)	2013-06-04	2015-12-30	Cellix Bio Private Ltd	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
EP3240779B1 (de)	2014-09-26	2020-10-28	Cellixbio Private Limited	Zusammensetzungen und verfahren zur behandlung von epilepsie- und lipidstörungen
ES2799309T3 (es)	2014-09-29	2020-12-16	Cellix Bio Private Ltd	Compuestos y composiciones para el tratamiento de esclerosis múltiple
CA2965449C (en)	2014-10-27	2020-11-10	Cellix Bio Private Limited	Three component salts of fumaric acid monomethyl ester with piperazine or ethylene diamine for the treatment of multiple sclerosis
US10208014B2 (en)	2014-11-05	2019-02-19	Cellix Bio Private Limited	Compositions and methods for the treatment of neurological disorders
US9150557B1 (en)	2014-11-05	2015-10-06	Cellix Bio Private Limited	Compositions and methods for the treatment of hyperglycemia
US9173877B1 (en)	2014-11-05	2015-11-03	Cellix Bio Private Limited	Compositions and methods for the treatment of local pain
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
US9175008B1 (en)	2014-11-05	2015-11-03	Cellix Bio Private Limited	Prodrugs of anti-platelet agents
US9284287B1 (en)	2014-11-05	2016-03-15	Cellix Bio Private Limited	Compositions and methods for the suppression of carbonic anhydrase activity
CN107207411A (zh)	2014-12-01	2017-09-26	塞尔利克斯生物私人有限公司	用于治疗多发性硬化的组合物和方法
US9206111B1 (en)	2014-12-17	2015-12-08	Cellix Bio Private Limited	Compositions and methods for the treatment of neurological diseases
ES2905771T3 (es)	2015-01-06	2022-04-12	Cellix Bio Private Ltd	Composiciones y procedimientos para el tratamiento de la inflamación y del dolor
CN108283000B (zh)	2015-09-23	2021-04-13	凯瑞康宁生物工程（武汉）有限公司	γ-羟基丁酸的前药及其组合物和用途
KR102510784B1 (ko) *	2017-03-30	2023-03-15	엑스더블유파마 리미티드	이환형 헤테로아릴 유도체 및 이의 제조 및 용도
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 (zh)	2018-09-30	2022-02-15	凯瑞康宁生物工程（武汉）有限公司	作为神经元组胺受体-3拮抗剂的化合物及其用途
WO2021127461A1 (en)	2019-12-20	2021-06-24	Xw Laboratories Limited	Methods of synthesizing 4-valyloxybutyric acid
KR102982616B1 (ko)	2020-06-18	2026-06-26	엑스더블유파마 리미티드	수용성 원료의약품의 약학적 과립화제
AU2021292406B2 (en)	2020-06-18	2024-03-14	XWPharma Ltd.	Controlled release granulations of water-soluble active pharmaceutical ingredients
WO2022020621A1 (en)	2020-07-24	2022-01-27	XWPharma Ltd.	Pharmaceutical compositions and pharmacokinetics of a gamma-hydroxybutyric acid derivative
AU2021357705B2 (en)	2020-10-05	2024-09-26	XWPharma Ltd.	Modified release compositions of a gamma-hydroxybutyric acid derivative
DK4308086T3 (da)	2021-03-19	2025-11-17	Xwpharma Ltd	Farmakokinetik af formuleringer med kombineret frigivelse af et gamma-hydroxysmørsyrederivat
WO2025216887A1 (en)	2024-04-11	2025-10-16	Dow Global Technologies Llc	High internal phase emulsion
US12605388B2 (en)	2024-09-25	2026-04-21	Azurity Pharmaceuticals Ireland Limited	Lamotrigine salts, co-crystals, and compositions

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL124029B1 (en) *	1979-06-01	1982-12-31	Wellcome Found	Process for preparing novel derivatives of 1,2,4-triazine
FR2492258A1 (fr) *	1980-10-17	1982-04-23	Pharmindustrie	Nouveau medicament a base d'amino-2 trifluoromethoxy-6 benzothiazole
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
EP0940139B1 (de) *	1991-02-08	2005-02-02	Scion Pharmaceuticals, Inc.	Substituierte Guanidine und Derivate hiervon als Modulatoren der Freisetzung von Neurotransmittern und neue Methode zur Identifizierung von Inhibitoren der Neurotransmitter-Freisetzung
FR2688138B1 (fr) *	1992-03-06	1995-05-05	Rhone Poulenc Rorer Sa	Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement de la sclerose laterale amyotrophique.

1992
- 1992-12-16 FR FR9215148A patent/FR2699077B1/fr not_active Expired - Fee Related
1993
- 1993-12-10 JP JP6513878A patent/JPH08504428A/ja active Pending
- 1993-12-10 KR KR1019950702460A patent/KR100298808B1/ko not_active Expired - Fee Related
- 1993-12-10 CZ CZ951546A patent/CZ154695A3/cs unknown
- 1993-12-10 WO PCT/FR1993/001227 patent/WO1994013296A1/fr not_active Ceased
- 1993-12-10 KR KR1019950702458A patent/KR950703965A/ko not_active Withdrawn
- 1993-12-10 UA UA95062798A patent/UA41906C2/uk unknown
- 1993-12-10 WO PCT/FR1993/001229 patent/WO1994013288A1/fr not_active Ceased
- 1993-12-10 US US08/424,529 patent/US5830907A/en not_active Expired - Lifetime
- 1993-12-10 EP EP94902019A patent/EP0674512B1/de not_active Expired - Lifetime
- 1993-12-10 PL PL93309346A patent/PL309346A1/xx unknown
- 1993-12-10 HU HU9501751A patent/HU217133B/hu not_active IP Right Cessation
- 1993-12-10 AU AU56540/94A patent/AU678795B2/en not_active Ceased
- 1993-12-10 KR KR1019950702459A patent/KR950703968A/ko not_active Withdrawn
- 1993-12-10 DE DE69317578T patent/DE69317578T2/de not_active Expired - Lifetime
- 1993-12-10 CA CA002151603A patent/CA2151603A1/fr not_active Abandoned
- 1993-12-10 SK SK787-95A patent/SK78795A3/sk unknown
- 1993-12-10 AT AT94902019T patent/ATE164067T1/de active
- 1993-12-10 PL PL93309347A patent/PL309347A1/xx unknown
- 1993-12-10 CZ CZ951547A patent/CZ154795A3/cs unknown
- 1993-12-10 AU AU56539/94A patent/AU5653994A/en not_active Abandoned
- 1993-12-10 JP JP6513879A patent/JPH08504429A/ja active Pending
- 1993-12-10 CZ CZ951545A patent/CZ284420B6/cs not_active IP Right Cessation
- 1993-12-10 EP EP94902018A patent/EP0674520A1/de not_active Ceased
- 1993-12-10 SK SK785-95A patent/SK78595A3/sk unknown
- 1993-12-10 EP EP94902802A patent/EP0674518A1/de not_active Withdrawn
- 1993-12-10 PL PL93309348A patent/PL309348A1/xx unknown
- 1993-12-10 SK SK786-95A patent/SK279759B6/sk not_active IP Right Cessation
- 1993-12-10 JP JP51388094A patent/JP3712239B2/ja not_active Expired - Fee Related
- 1993-12-10 DK DK94902019.2T patent/DK0674512T3/da active
- 1993-12-10 HU HU9501752A patent/HUT71839A/hu unknown
- 1993-12-10 WO PCT/FR1993/001228 patent/WO1994013298A1/fr not_active Ceased
- 1993-12-10 HU HU9501753A patent/HUT71812A/hu unknown
- 1993-12-10 CA CA002151601A patent/CA2151601A1/fr not_active Abandoned
- 1993-12-10 AU AU57020/94A patent/AU5702094A/en not_active Abandoned
- 1993-12-10 CA CA002151604A patent/CA2151604C/fr not_active Expired - Fee Related
- 1993-12-10 ES ES94902019T patent/ES2113635T3/es not_active Expired - Lifetime
- 1993-12-10 RU RU95114405A patent/RU2142800C1/ru not_active IP Right Cessation
- 1993-12-13 MX MX9307884A patent/MX9307884A/es unknown
- 1993-12-13 MX MX9307883A patent/MX9307883A/es unknown
- 1993-12-13 MX MX9307882A patent/MX9307882A/es not_active Application Discontinuation
- 1993-12-15 ZA ZA939400A patent/ZA939400B/xx unknown
- 1993-12-15 ZA ZA939399A patent/ZA939399B/xx unknown
- 1993-12-15 ZA ZA939401A patent/ZA939401B/xx unknown
- 1993-12-16 IL IL10805293A patent/IL108052A0/xx unknown
- 1993-12-16 IL IL10805393A patent/IL108053A0/xx unknown
- 1993-12-16 IL IL10805193A patent/IL108051A/en not_active IP Right Cessation
1995
- 1995-06-06 NO NO952230A patent/NO307027B1/no not_active IP Right Cessation
- 1995-06-06 NO NO952228A patent/NO952228L/no unknown
- 1995-06-06 NO NO952229A patent/NO952229L/no unknown
1998
- 1998-03-19 GR GR970403094T patent/GR3026403T3/el unknown

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9413298A1 *

Also Published As

Publication number	Publication date
CZ154795A3 (en)	1995-11-15
AU5653994A (en)	1994-07-04
PL309348A1 (en)	1995-10-02
ATE164067T1 (de)	1998-04-15
US5830907A (en)	1998-11-03
FR2699077A1 (fr)	1994-06-17
MX9307882A (es)	1994-06-30
AU5702094A (en)	1994-07-04
NO307027B1 (no)	2000-01-31
KR100298808B1 (ko)	2001-11-22
NO952230D0 (no)	1995-06-06
NO952229D0 (no)	1995-06-06
CZ154595A3 (en)	1995-11-15
HU217133B (hu)	1999-11-29
NO952228D0 (no)	1995-06-06
AU678795B2 (en)	1997-06-12
NO952230L (no)	1995-06-06
SK279759B6 (sk)	1999-03-12
CA2151601A1 (fr)	1994-06-23
IL108053A0 (en)	1994-04-12
NO952228L (no)	1995-06-06
NO952229L (no)	1995-06-06
EP0674512A1 (de)	1995-10-04
IL108052A0 (en)	1994-04-12
DE69317578T2 (de)	1998-07-23
MX9307884A (es)	1994-06-30
IL108051A (en)	1999-05-09
ZA939399B (en)	1994-08-22
HUT71839A (en)	1996-02-28
DK0674512T3 (da)	1998-05-25
FR2699077B1 (fr)	1995-01-13
CA2151604A1 (fr)	1994-06-23
HU9501751D0 (en)	1995-08-28
KR950703954A (ko)	1995-11-17
CZ154695A3 (en)	1995-11-15
KR950703968A (ko)	1995-11-17
EP0674512B1 (de)	1998-03-18
JP3712239B2 (ja)	2005-11-02
JPH08504428A (ja)	1996-05-14
RU2142800C1 (ru)	1999-12-20
ZA939400B (en)	1994-08-19
AU5654094A (en)	1994-07-04
SK78795A3 (en)	1996-05-08
DE69317578D1 (de)	1998-04-23
JPH08504429A (ja)	1996-05-14
HUT71814A (en)	1996-02-28
JPH08504430A (ja)	1996-05-14
IL108051A0 (en)	1994-04-12
HU9501753D0 (en)	1995-08-28
CA2151603A1 (fr)	1994-06-23
SK78595A3 (en)	1996-05-08
HU9501752D0 (en)	1995-08-28
CA2151604C (fr)	2005-09-20
MX9307883A (es)	1994-06-30
WO1994013298A1 (fr)	1994-06-23
WO1994013296A1 (fr)	1994-06-23
ZA939401B (en)	1994-08-19
GR3026403T3 (en)	1998-06-30
PL309347A1 (en)	1995-10-02
HUT71812A (en)	1996-02-28
KR950703965A (ko)	1995-11-17
CZ284420B6 (cs)	1998-11-11
UA41906C2 (uk)	2001-10-15
EP0674518A1 (de)	1995-10-04
ES2113635T3 (es)	1998-05-01
PL309346A1 (en)	1995-10-02
SK78695A3 (en)	1996-05-08
WO1994013288A1 (fr)	1994-06-23

Legal Events

Date	Code	Title	Description
1995-08-18	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
1995-10-04	17P	Request for examination filed	Effective date: 19950602
1995-10-04	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
1996-03-29	GRAG	Despatch of communication of intention to grant	Free format text: ORIGINAL CODE: EPIDOS AGRA
1996-05-15	17Q	First examination report despatched	Effective date: 19960402
1996-12-19	STAA	Information on the status of an ep patent application or granted ep patent	Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED
1997-02-05	18R	Application refused	Effective date: 19960921

Publication	Publication Date	Title
EP0674512B1 (de)	1998-03-18	Verwendung von riluzole zur behandlung von traumatischen neurologischen-schädigungen
EP0678023B1 (de)	1996-10-23	Verwendung von riluzol zur behandlung von parkinson und den parkinson-syndromen
WO1994020103A1 (fr)	1994-09-15	Application du riluzole dans le traitement du neuro-sida
FR2619713A1 (fr)	1989-03-03	Application de l'amino-2 trifluoromethoxy-6 benzothiazole pour obtenir un medicament destine au traitement des troubles du sommeil et de la depression
DE69906969T2 (de)	2003-12-11	Verwendung von aryl(oder heteroaryl)-azolylcarbinolderivaten in der herstellung von medikamenten zur behandlung von neurogenen entzündungen
FR2699079A1 (fr)	1994-06-17	Application d'anticonvulsivants dans le traitement de lésions neurologiques liées à des traumatismes.
FR2699078A1 (fr)	1994-06-17	Application de la lamotrigine dans le traitement de lésions neurologiques liées à des traumatismes.
EP1212119A1 (de)	2002-06-12	Verwendung von cyamemazin zur behandlung von entwöhnungserscheinungen der benzodiazepinbehandlung
EP1052989B1 (de)	2003-07-30	Verwendung von 2-amino-6-trifluoromethoxybenzothiazol zur herstellung eines arzneimittels zur vorbeugung oder behandlung von zerebellumkrankheiten
EP0374042A2 (de)	1990-06-20	Verwendung von Carbipramin zur Herstellung eines Medikaments zur Behandlung von Angstzuständen und von Schlafstörungen
EP0678022B1 (de)	1996-11-13	Verwendung von riluzol zum schutz gegen strahlenschäden
FR2700114A1 (fr)	1994-07-08	Application de la lamotrigine dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens.
FR2700115A1 (fr)	1994-07-08	Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens.
NL7908286A (nl)	1980-05-16	Preparaat voor het behandelen van fysiologische aandoe- ningen bij mammaliaspecies, die worden gekenmerkt door aberrante hoogfrequentieontlading van zenuwvezels.