SK279645B6 - Použitie karbamazepínu a oxkarbazepínu na prípravu - Google Patents
Použitie karbamazepínu a oxkarbazepínu na prípravu Download PDFInfo
- Publication number
- SK279645B6 SK279645B6 SK866-95A SK86695A SK279645B6 SK 279645 B6 SK279645 B6 SK 279645B6 SK 86695 A SK86695 A SK 86695A SK 279645 B6 SK279645 B6 SK 279645B6
- Authority
- SK
- Slovakia
- Prior art keywords
- carbamazepine
- oxcarbazepine
- disease
- preparation
- parkinsonian
- Prior art date
Links
- 229960000623 carbamazepine Drugs 0.000 title claims abstract description 9
- 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 abstract description 9
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 229960001816 oxcarbazepine Drugs 0.000 title claims abstract description 8
- 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 abstract description 8
- 208000018737 Parkinson disease Diseases 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 229940079593 drug Drugs 0.000 title abstract 2
- 239000001961 anticonvulsive agent Substances 0.000 claims abstract description 6
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 7
- 229960003965 antiepileptics Drugs 0.000 abstract description 2
- 208000027089 Parkinsonian disease Diseases 0.000 abstract 1
- 230000001773 anti-convulsant effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 12
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 8
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 8
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 210000001577 neostriatum Anatomy 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- 206010034010 Parkinsonism Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 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
- 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
- 229920002472 Starch Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 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
- 239000008101 lactose Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- -1 theophyl 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
- 239000000080 wetting agent Substances 0.000 description 2
- 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
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 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
- 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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 101710138657 Neurotoxin Proteins 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
- 239000005662 Paraffin oil Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 238000010165 Scheffé test Methods 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
- 239000000654 additive Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical group C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008393 encapsulating 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
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 239000004922 lacquer Substances 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
- 239000011707 mineral Substances 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 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
- 239000000377 silicon dioxide Substances 0.000 description 1
- HKQLYXRSURHCPY-UHFFFAOYSA-M sodium;ethanol;benzoate Chemical compound [Na+].CCO.[O-]C(=O)C1=CC=CC=C1 HKQLYXRSURHCPY-UHFFFAOYSA-M 0.000 description 1
- XXEGCVDKHPRBPJ-UHFFFAOYSA-M sodium;propane-1,2-diol;hydroxide Chemical compound [OH-].[Na+].CC(O)CO XXEGCVDKHPRBPJ-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 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
- 238000003756 stirring Methods 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
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 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
- A61K31/55—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
- 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
- A61K31/41—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
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines Containing Plant Substances (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Oblasť techniky
Vynález sa týka nového terapeutického použitia protikŕčových Činidiel karbamazepínu a oxkarbazepínu alebo farmaceutický prijateľných solí týchto zlúčenín.
Doterajší stav techniky
Karbamazepín a oxkarbazepín sa opísali ako protikŕčové činidlá a antiepileptiká v patentovom dokumente EP 50589.
Podstata vynálezu
Teraz sa zistilo, že tieto zlúčeniny sa môžu tiež použiť pri liečení Parkinsonovej choroby a Parkinsonových syndrómov.
Je známe, že neurotoxín MPTP (l-metyl-4-fenyl-l,2,3,6-tetrahydropyridín indukuje syndróm, ktorý je obdobný s Parkinsonovou chorobou. Tento syndróm je dôsledkom degenerácie nigrostriatálnych dopaminergných neurónov primátov (R.S.Bums a kol., Proc.Natl.Acad.Sci., 80, 4546 (1983), ľudí (J. W. Langston a kol., Science, 219, 979-980 (1983) a myší (R. E. Heikkila a kol., Science, 224, 1451-1453 (1984).
Účinnosť uvedených produktov sa demonštrovala u myšiach meraním zníženia hladín striatálneho dopamínu, kyseliny 3,4-dihydroxyfenyloctovej a kyseliny homovanilovej, indukovaných produktom MPTP v porovnaní so znížením uvedených hladín v kontrolnej skupine pokusných zvierat.
Myšiam (C57BL/6) s telesnou hmotnosťou 20 až 25 g sa trikrát v dvojhodinových intervaloch injikuje 15 mg/kg produktu MPTP. Tridsať minút pred prvou injekciou a potom 2 hodiny a 30 minút, 5 hodín a 30 minút a 7 hodín a 30 minút po prvej injekcii MPTP sa podá podľa použitého produktu 1 až 40 mg/kg testovaného produktu. V priebehu nasledujúcich troch dní sa podáva dvakrát denne podľa použitého produktu 1 až 40 mg/kg testovaného produktu. 8 dní po injekcii produktu MPTP sa myši utratia. Vypreparované striatum sa prechováva pri teplote -70 °C až do okamihu jeho analýzy. Obsahy dopamínu, kyseliny 3,4-dihydroxyfenyloctovej a kyseliny homovanilovej sa určia veľmi rýchlou kvapalinovou chromatografiou s použitím elektrochemickej detekcie. Štatistické analýzy sa uskutočnia s použitím systému Anova a následného Scheffeho testu.
Výsledky získané pri použití dávok 20 mg/kg karbamazepínu sú uvedené v nasledujúcej tabuľke.
Tabuľka
| Hladina kyseliny* v 3,4-dihydroxyfenyloctovej v paol/mg v striate (v t vzhľadoa. na kontrolnú skupinu zvierat) | Hladina kyseliny hoaovanilovej v pmol/tng v striate (v » vzhľadom na kontrolnú skap, zvierat) | Hladina dopamínu v prtol/eg v striate (v t vzhľadom na kontrolnú skupinu zvierat) | |
| Kontrolná | |||
| skupina | 54+3 | 95+3 | 856+27 |
| svierat | |||
| Zvierati pri- 22+4 | 62+3 | 415+22 | |
| 1íma*tíXce | iba (-59 t) | (-35 %] | (-52 %) |
| MPTP | |||
| Zvierati | o*et- 4S±< | 90±6 | 7«5±30 |
| rend fcarbaaaze- (-12 t J | (-3 | (-11 |
plno
Z uvedenej tabuľky je zrejmé, že uvedené produkty sú schopné zabraňovať zníženiu hladín dopamínu, kyseliny 3,4-dihydroxyfenyloctovej a kyseliny homovanilovej, indukovanému produktom MPTP v striate.
Ako farmaceutický prijateľné soli sa môžu predovšetkým uviesť adičné soli s minerálnymi kyselinami, akými sú hydrochlorid, sulfát, nitrát, fosfát, alebo s organickými kyselinami, akými sú propionát, sukcinát, oxalát, benzoát, fumarát, maleát, metánsulfonát, izetionát, teofilín-acetát, salicylát, fenolftalinát, metylén-bis-beta-oxynaftoát alebo substitučné deriváty týchto derivátov.
Liečivá sa tvoria aspoň účinnou látkou vo voľnej forme alebo vo forme adičnej soli s farmaceutický prijateľnou kyselinou, v čistom stave alebo vo forme prostriedku, v ktorom jc účinná látka v kombinácii s ľubovoľným iným farmaceutický zlučiteľným produktom, ktoiý môže byť inertný alebo fyziologicky aktívny. Liečivá podľa vynálezu sa môžu použiť perorálne alebo parenterálne.
Ako pevné prostriedky na perorálne podanie sa môžu použiť tablety, pilulky, prášky (želatínové kapsuly, vrecúška) alebo granuly, V týchto prostriedkoch je účinná látka podľa vynálezu zmiešaná s jedným alebo niekoľkými inertnými riedidlami, akými sú škrob, celulóza, sacharóza, laktóza alebo silika, pričom uvedené miešanie sa realizuje pod prúdom argónu. Tieto prostriedky môžu tiež obsahovať iné látky než riedidlá, a to napríklad jedno alebo niekoľko mazív, akými sú stearát horečnatý’ alebo mastenec, farbivo, zapúzdrovaciu látku (dražé) alebo lak.
Ako kvapalné prostriedky na perorálne podanie sa môžu použiť roztoky, suspenzie, emulzie, sirupy a elixíry majúce farmaceutický prijateľný charakter a obsahujúce inertné riedidlá, akými sú voda, etanol, glycerol, rastlinné oleje alebo parafínový olej. Tieto prostriedky môžu obsahovať aj iné látky než riedidlá, a to napríklad namáčadlá, sladidlá, zhutňovadlá, aromatické látky a stabilizátory.
Ako sterilné prostriedky na parenterálne podanie sa môžu výhodne použiť vodné alebo nevodné roztoky, suspenzie alebo emulzie. Ako rozpúšťadlo alebo vehikulum sa môžu použiť voda, propylénglykol, polyetylénglykol, rastlinné oleje, najmä olivový olej, injikovateľné organické estery, napríklad etyloleát, alebo ďalšie vhodné organické rozpúšťadlá. Tieto prostriedky môžu tiež obsahovať prísady, najmä namáčadlá, izotonizujúce činidlá, emulgačné činidlá, dispergačné činidlá a stabilizátory. Sterilizácia sa môže uskutočniť niekoľkými spôsobmi, napríklad aseptizujúcou filtráciou, zavedením sterilizačného činidla, ožiarením alebo zohrievaním. Tieto prostriedky sa môžu taktiež pripraviť vo forme pevných sterilných prostriedkov, ktoré sa môžu rozpustiť bezprostredne pred podaním v sterilnej vode alebo v inom injikovateľnom sterilnom prostredí.
Dávky budú závisieť od požadovaného účinku, dobe liečenia a od použitého spôsobu podania. Tieto dávky všeobecne tvoria 50 až 400 mg denne pri perorálnom podaní dospelému pacientovi pri, použití jednotkových dávkových foriem od 25 do 200 mg účinnej látky.
Vhodné dávkovanie všeobecne určí lekár v závislosti od veku, hmotnosti a všetkých ostatných charakteristík liečeného pacienta.
Príklady uskutočnenia vynálezu
Príklad A
Zvyčajnou technikou sa pripravia tablety obsahujúce 50 mg účinnej látky s nasledujúcim zložením:
účinná látka 50mg manitol 64mg mikrokryštalická celulóza50 mg polyvidonový excipient12 mg nátriumkarboxymetylškrob16 mg mastenec 4mg stearát horečnatý 2mg bezvodná koloidná silika2 mg tický prijateľných solí týchto zlúčenín na prípravu liečiv určených na liečenie Parkinsonovej choroby a Parkinsonových syndrómov.
2. Použitie podľa nároku 1 na získanie liečiva obsahujúceho 25 až 200 mg karbamazepinu alebo oxkarbazepínu.
Koniec dokumentu zmes metylhydroxypropylcelulózy, polyetylénglykolu 6000 a oxidu titaničitého (72:3,5:24,5)-doplniť na hmotnosť finálnej zapuzdrenej tablety 245 mg.
Príklad B
Zvyčajnou technikou sa pripravia želatínové tobolky obsahujúce 50 mg účinnej látky s nasledujúcim zložením:
účinná látka 50mg celulóza18 mg laktóza 55mg koloidná silika 1mg nátriumkarboxymetylškrob 10 mg mastenec10 mg stearát horečnatý' 1mg.
Príklad C
Pripraví sa injikovateľný roztok obsahujúci 10 mg účinnej látky s nasledujúcim zložením:
mg mg
0,06 cm^ mg
0,4 crrĎ mg
1,6 cm^ účinná látka kyselina benzoová benzylalkohol benzoát sodný etanol (95%) hydroxid sodný propylénglykol voda doplniť do 4 cmÁ
Vynález sa tiež týka spôsobu prípravy liečiv použiteľných pri liečení Parkinsonovej choroby a Parkinsonových syndrómov, ktorého podstata tkvie v tom, že sa protikŕčové činidlo zvolené z množiny zahŕňajúcej karbamazepín a oxkarbazepín alebo farmaceutický prijateľné soli týchto zlúčenín zmiešajú s jedným alebo niekoľkými kompatibilnými a farmaceutický prijateľnými riedidlami a/alebo s jednou alebo niekoľkými kompatibilnými a farmaceutický prijateľnými prísadami.
Vynález sa tiež týka spôsobu liečenia cicavca, najmä človeka trpiaceho Parkinsonovou chorobou alebo Parkinsonovými syndrómami, ktorého podstata tkvie v tom, že sa podá účinné množstvo karbamazepinu alebo oxkarbazepínu alebo farmaceutický prijateľných solí týchto zlúčenín.
Claims (1)
- PATENTOVÉ NÁROKY1. Použitie protikŕčových činidiel zvolených z množiny zahŕňajúcej karbamazepín a oxkarbazepín alebo farmaceu-
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9300074A FR2700117B1 (fr) | 1993-01-07 | 1993-01-07 | Application d'anticonvulsivants dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens. |
| PCT/FR1994/000004 WO1994015610A1 (fr) | 1993-01-07 | 1994-01-03 | Application de la carbamazepine et de l'oxcarbazepine dans le traitement de la maladie de parkinson et des syndromes parkinsoniens |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK86695A3 SK86695A3 (en) | 1996-05-08 |
| SK279645B6 true SK279645B6 (sk) | 1999-01-11 |
Family
ID=9442862
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK866-95A SK279645B6 (sk) | 1993-01-07 | 1994-01-03 | Použitie karbamazepínu a oxkarbazepínu na prípravu |
| SK867-95A SK279758B6 (sk) | 1993-01-07 | 1994-01-03 | Parkinsonovejchoroby a parkinsonových syndrómov |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK867-95A SK279758B6 (sk) | 1993-01-07 | 1994-01-03 | Parkinsonovejchoroby a parkinsonových syndrómov |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US5658900A (sk) |
| EP (2) | EP0678023B1 (sk) |
| JP (2) | JPH08505379A (sk) |
| KR (2) | KR100298807B1 (sk) |
| AT (2) | ATE144420T1 (sk) |
| AU (3) | AU677279B2 (sk) |
| CA (2) | CA2153341A1 (sk) |
| CZ (2) | CZ284928B6 (sk) |
| DE (2) | DE69400799T2 (sk) |
| DK (2) | DK0678026T3 (sk) |
| ES (2) | ES2091689T3 (sk) |
| FR (1) | FR2700117B1 (sk) |
| GR (2) | GR3020975T3 (sk) |
| HU (2) | HUT72074A (sk) |
| IL (3) | IL108285A0 (sk) |
| MX (2) | MX9307885A (sk) |
| NO (2) | NO307495B1 (sk) |
| PL (2) | PL309594A1 (sk) |
| RU (1) | RU2221563C2 (sk) |
| SK (2) | SK279645B6 (sk) |
| UA (1) | UA29464C2 (sk) |
| WO (3) | WO1994015610A1 (sk) |
| ZA (3) | ZA9426B (sk) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6119094A (en) * | 1996-02-29 | 2000-09-12 | Electronic Data Systems Corporation | Automated system for identifying alternate low-cost travel arrangements |
| US6417210B1 (en) * | 1998-01-09 | 2002-07-09 | Mor-Research Applications Ltd. | Treatment of dyskinesias and Parkinson's disease with riluzole and levodopa |
| AU1780699A (en) * | 1998-01-09 | 1999-07-26 | Mor Research Applications Ltd. | Treatment of dyskinesias |
| FR2774592B1 (fr) * | 1998-02-06 | 2000-03-17 | Rhone Poulenc Rorer Sa | Application du 2-amino-6-trifluoromethoxybenzothiazole pour la prevention ou le traitement des dysfonctionnements du cervelet |
| FR2777781B1 (fr) * | 1998-04-24 | 2004-04-09 | Rhone Poulenc Rorer Sa | Associations riluzole et l-dopa pour le traitement de la maladie de parkinson |
| FR2787028B1 (fr) | 1998-12-15 | 2002-10-18 | Aventis Pharma Sa | Utilisation du riluzole dans le traitement des traumatismes acoustiques |
| US6506378B1 (en) * | 1998-12-16 | 2003-01-14 | Arch Development Corporation | Vesicular monoamine transporter gene therapy in Parkinson's disease |
| FR2801793B1 (fr) * | 1999-12-01 | 2003-07-04 | Aventis Pharma Sa | Association d'une ergoline et de riluzole et son utilisation comme medicament |
| JP2004526706A (ja) * | 2001-02-12 | 2004-09-02 | テバ ファーマシューティカル インダストリーズ リミティド | オクスカルバゼピンの新しい結晶形態及びそれらの調製方法 |
| US20050070524A1 (en) * | 2003-06-06 | 2005-03-31 | Pharmacia Corporation | Compositions of a cyclooxygenase-2 selective inhibitor and an anticonvulsant agent for the treatment of central nervous system disorders |
| WO2005037276A1 (en) * | 2003-10-09 | 2005-04-28 | Aventis Pharma S.A. | Use of riluzole for the treatment of essential tremor |
| CA2471666C (en) * | 2004-06-18 | 2009-10-13 | Apotex Pharmachem Inc. | An improved process for the preparation of oxcarbazepine and related intermediates |
| EP1924326B1 (en) | 2005-08-25 | 2016-10-12 | Steven Michael Weiss | Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption in coronary blood flow |
| US20070248684A1 (en) * | 2006-01-31 | 2007-10-25 | Sigal Blau | Pharmaceutical formulations of oxcarbazepine and methods for its preparation |
| AU2006337141A1 (en) * | 2006-01-31 | 2007-08-09 | Teva Pharmaceutical Industries Ltd. | Oxcarbazepine pharmaceutical formulation and its method of preparation, wherein oxcarbazepine has a broad and multi-modal particle size distribution |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| ES2360423T3 (es) * | 2006-04-26 | 2011-06-03 | Supernus Pharmaceuticals, Inc. | Preparaciones de liberación controlada de oxcarbazepina que tienen perfil de liberación sigmoidal. |
| US20110002972A1 (en) * | 2007-09-14 | 2011-01-06 | Scil Technology Gmbh | Neuroendocrine factors for treatment of degenerative diseases |
| EP3006024B1 (en) | 2009-01-20 | 2019-03-20 | Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center | Benzoic acid or salts thereof to enhance the activity of a neuropharmaceutical |
| WO2011017319A1 (en) | 2009-08-03 | 2011-02-10 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Methods of treating disorders associated with protein polymerization |
| US9072772B2 (en) | 2009-11-05 | 2015-07-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | Methods of treating disorders associated with protein aggregation |
| US8809617B2 (en) * | 2009-11-05 | 2014-08-19 | The University of Pittsburgh—Of the Commonwealth System of Higher Education | Automated high-content live animal drug screening using C. elegans |
| US9463186B2 (en) | 2013-04-15 | 2016-10-11 | Northwestern University | Treatment for dopaminergic disorders |
| CN109563024B (zh) | 2016-06-13 | 2023-06-06 | 心悦生医股份有限公司 | 苯甲酸锂的共晶及其用途 |
| CN109563018A (zh) | 2016-06-13 | 2019-04-02 | 心悦生医股份有限公司 | 苯甲酸钠的共晶及其用途 |
| US11369579B2 (en) | 2016-10-24 | 2022-06-28 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
| US10336679B2 (en) | 2016-10-24 | 2019-07-02 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
| US10322114B2 (en) | 2017-07-31 | 2019-06-18 | Above And Beyond Nb, Llc | Formulation of a riluzole solution with beta-cyclodextrins |
| US10098861B1 (en) | 2017-10-24 | 2018-10-16 | Syneurx International (Taiwan) Corp. | Pharmaceutical composition comprising sodium benzoate compound and clozapine, and uses thereof |
| CA3151459A1 (en) * | 2019-09-20 | 2021-03-25 | Ana PEREIRA | Controlled release formulations of riluzole and their uses |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2948718A (en) * | 1960-08-09 | New n-heterocyclic compounds | ||
| CH500196A (de) * | 1969-03-10 | 1970-12-15 | Ciba Geigy Ag | Verfahren zur Herstellung von neuen Azepinderivaten |
| 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 |
| DE4118740A1 (de) * | 1991-06-05 | 1992-12-10 | Schering Ag | Neue kombinationspraeparate zur behandlung des morbus parkinson |
| FR2699077B1 (fr) * | 1992-12-16 | 1995-01-13 | Rhone Poulenc Rorer Sa | Application d'anticonvulsivants dans le traitement de lésions neurologiques liées à des traumatismes. |
-
1993
- 1993-01-07 FR FR9300074A patent/FR2700117B1/fr not_active Expired - Lifetime
- 1993-12-13 MX MX9307885A patent/MX9307885A/es not_active IP Right Cessation
-
1994
- 1994-01-03 SK SK866-95A patent/SK279645B6/sk unknown
- 1994-01-03 DE DE69400799T patent/DE69400799T2/de not_active Expired - Lifetime
- 1994-01-03 WO PCT/FR1994/000004 patent/WO1994015610A1/fr active IP Right Grant
- 1994-01-03 DK DK94903936.6T patent/DK0678026T3/da active
- 1994-01-03 DK DK94903935.8T patent/DK0678023T3/da active
- 1994-01-03 CA CA002153341A patent/CA2153341A1/fr not_active Abandoned
- 1994-01-03 EP EP94903935A patent/EP0678023B1/fr not_active Expired - Lifetime
- 1994-01-03 WO PCT/FR1994/000003 patent/WO1994015601A1/fr active IP Right Grant
- 1994-01-03 PL PL94309594A patent/PL309594A1/xx unknown
- 1994-01-03 KR KR1019950702793A patent/KR100298807B1/ko not_active IP Right Cessation
- 1994-01-03 ES ES94903936T patent/ES2091689T3/es not_active Expired - Lifetime
- 1994-01-03 CA CA002153340A patent/CA2153340C/fr not_active Expired - Lifetime
- 1994-01-03 CZ CZ951764A patent/CZ284928B6/cs not_active IP Right Cessation
- 1994-01-03 UA UA95073383A patent/UA29464C2/uk unknown
- 1994-01-03 AU AU58189/94A patent/AU677279B2/en not_active Ceased
- 1994-01-03 AU AU58188/94A patent/AU684059B2/en not_active Expired
- 1994-01-03 DE DE69400435T patent/DE69400435T2/de not_active Expired - Fee Related
- 1994-01-03 AT AT94903935T patent/ATE144420T1/de active
- 1994-01-03 EP EP94903936A patent/EP0678026B1/fr not_active Expired - Lifetime
- 1994-01-03 ES ES94903935T patent/ES2092890T3/es not_active Expired - Lifetime
- 1994-01-03 CZ CZ951765A patent/CZ284363B6/cs unknown
- 1994-01-03 HU HU9502065A patent/HUT72074A/hu unknown
- 1994-01-03 US US08/446,735 patent/US5658900A/en not_active Expired - Fee Related
- 1994-01-03 SK SK867-95A patent/SK279758B6/sk not_active IP Right Cessation
- 1994-01-03 HU HU9502063A patent/HU217136B/hu unknown
- 1994-01-03 WO PCT/FR1994/000005 patent/WO1994015607A1/fr active Application Filing
- 1994-01-03 PL PL94309596A patent/PL309596A1/xx unknown
- 1994-01-03 JP JP6515743A patent/JPH08505379A/ja active Pending
- 1994-01-03 AT AT94903936T patent/ATE141792T1/de not_active IP Right Cessation
- 1994-01-03 US US08/446,734 patent/US5674885A/en not_active Expired - Lifetime
- 1994-01-03 JP JP06515742A patent/JP3120153B2/ja not_active Expired - Fee Related
- 1994-01-03 RU RU2000127693/15A patent/RU2221563C2/ru active
- 1994-01-03 AU AU58190/94A patent/AU5819094A/en not_active Abandoned
- 1994-01-04 ZA ZA9426A patent/ZA9426B/xx unknown
- 1994-01-04 ZA ZA9432A patent/ZA9432B/xx unknown
- 1994-01-04 ZA ZA9428A patent/ZA9428B/xx unknown
- 1994-01-05 MX MX9400287A patent/MX9400287A/es unknown
- 1994-01-06 IL IL10828594A patent/IL108285A0/xx unknown
- 1994-01-06 IL IL10828494A patent/IL108284A/en not_active IP Right Cessation
- 1994-01-06 IL IL10828694A patent/IL108286A0/xx unknown
-
1995
- 1995-06-12 NO NO952309A patent/NO307495B1/no not_active IP Right Cessation
- 1995-06-12 NO NO952310A patent/NO952310D0/no unknown
- 1995-07-06 KR KR1019950702794A patent/KR960700059A/ko not_active Application Discontinuation
-
1996
- 1996-09-11 GR GR960400811T patent/GR3020975T3/el unknown
- 1996-10-24 GR GR960401906T patent/GR3021438T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK279645B6 (sk) | Použitie karbamazepínu a oxkarbazepínu na prípravu | |
| EP0385517B1 (en) | Medicaments for the treatment of emesis | |
| RU2110260C1 (ru) | Средство для лечения латерального амиотрофического склероза | |
| RU2260428C2 (ru) | Фармацевтическая композиция, содержащая производное бензамида и обладающая повышенной растворимостью и поглощаемостью при оральном применении | |
| KR0164435B1 (ko) | 비만증 치료용 약제학적 조성물 | |
| US20020197318A1 (en) | Compositions | |
| SK107595A3 (en) | Use of anticonvulsive agents for treating aids-related neural disorders | |
| CA2370834C (en) | Use of saredutant and the pharmaceutically acceptable salts thereof to produce medicaments used to treat or prevent mood disorders, adjustment disorders or mixed anxiety-depression disorders | |
| JP3585045B2 (ja) | ミトコンドリア疾病の処置におけるリルゾールの適用 | |
| EP1408977B1 (en) | A combination therapy for the treatment of heart failure | |
| US4906638A (en) | Dextromethorphan potentiator for anticonvulsant composition and method | |
| US6534500B2 (en) | Use of cyamemazine in the treatment of abrupt benzodiazephine withdrawal | |
| US4312879A (en) | Clonidine and lofexidine as antidiarrheal agents | |
| US20060287353A1 (en) | Method for preventing or treating ischemia-or hemorrhage-induced brain damage using a macrolide compound | |
| EP0605723A1 (en) | Blood lipid metabolism ameliorant | |
| HU206623B (en) | Process for producing pharmaceutical compositions containing imidazo-pyrrolo-benzodiazepine as antipsychotic active component | |
| JPH03502802A (ja) | 抗嘔吐性エルゴリン誘導体 | |
| EP0071563A1 (en) | Trans-dihyldrolisuride antipsychotic | |
| US4956362A (en) | Use of carpipramine for the treatment of anxiety and sleep disorders | |
| KR960011773B1 (ko) | 궤양의 예방 및 치료용 의약 조성물 | |
| JPS6254769B2 (sk) | ||
| FR2700114A1 (fr) | Application de la lamotrigine dans le traitement de la maladie de Parkinson et des syndromes parkinsoniens. |