SK86795A3 - Application of riluzole in the treatment of parkinson's disease and parkinsonian syndromes - Google Patents
Application of riluzole in the treatment of parkinson's disease and parkinsonian syndromes Download PDFInfo
- Publication number
- SK86795A3 SK86795A3 SK867-95A SK86795A SK86795A3 SK 86795 A3 SK86795 A3 SK 86795A3 SK 86795 A SK86795 A SK 86795A SK 86795 A3 SK86795 A3 SK 86795A3
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- Slovakia
- Prior art keywords
- riluzole
- parkinson
- treatment
- disease
- pharmaceutically acceptable
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- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229960004181 riluzole Drugs 0.000 title claims abstract description 16
- 208000018737 Parkinson disease Diseases 0.000 title claims abstract description 9
- 208000027089 Parkinsonian disease Diseases 0.000 title abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 206010034010 Parkinsonism Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 229940079593 drug Drugs 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
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
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- 101710138657 Neurotoxin Proteins 0.000 description 4
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- 239000004480 active ingredient Substances 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- 239000002581 neurotoxin Substances 0.000 description 4
- 231100000618 neurotoxin Toxicity 0.000 description 4
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
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- 206010002091 Anaesthesia Diseases 0.000 description 1
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- 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
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- 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
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- 229910019142 PO4 Inorganic materials 0.000 description 1
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- 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
- 229920002472 Starch Polymers 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
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
- 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
- 239000003326 hypnotic agent Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 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
- 238000004811 liquid chromatography Methods 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
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- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 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
- 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
- 229940096364 riluzole 50 mg Drugs 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
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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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
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- 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)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Plant Substances (AREA)
Description
Použitie riluzolu pri liečení Parkinsonovej choroby a Parkinsonových syndrómov
Oblasť techniky
Vynález sa týka nového terapeutického použitia riluzolu (6-trifluórmetoxy-2-aminobenzotiazol) alebo farmaceutický prijateľných solí tejto zlúčeniny.
Doterajší stav techniky
Riluzol je použiteľný ako protikŕčové liečivo a ďalej ako anxiolytikum a hypnotikum (európsky patent EP 50551), pri liečení schizofrénie (európsky patent EP 305276), pri liečení porúch spánku a depresie (európsky patent EP 305277), pri liečení cerebrovaskulárnych porúch a ako anestetikum (európsky patent 282971).
Podstata vynálezu
Teraz sa zistilo, že táto zlúčenina sa môže tiež použiť pri liečení Parkinsonovej choroby a Parkinsonových syndrómov.
Je známe, že neurotoxín MPTP (l-metyl-4-fenyl-l,2,3,6tetrahydropyridín indukuje syndróm, ktorý je obdobný s Parkinsonovou chorobou. Tento syndróm je dôsledkom degenerácie nigrostriatálnych dopaminergných neurónov u primátov (R.S.Burns a kol., Proc.Natl.Acad.Sci., 80, 4546 (1983), u ľudí (J.W.Langston a kol., Science, 219, 979-980 (1983) a u myší (R.E.Heikkila a kol., Science, 224, 1451-1453 (1984).
Účinnosť riluzolu sa demonštrovala u myší meraním zníženej hladiny striatálneho a kortikálneho dopamínu indukovaného neurotoxínom MPTP a porovnaním získaných výsledkov s výsledkami získanými pre skupinu kontrolných pokusných zvierat.
Myšiam (C57BL/6) s telesnou hmotnosťou 20 až 25 g sa trikrát v dvojhodinovom intervale injikuje 15 mg/kg neurotoxínu MPTP. Tridsať minút pred prvou injekciou neurotoxínu MPTP a potom 2 hodiny a 30 minút, 5 hodín a 30 minút a 7 hodín a 30 minút po prvej injekcii neurotoxínu MPTP sa podá v závislosti na použitom produkte 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. Pokusné myši sa utratia 8 dní po injekcii MPTP. Myšiam sa odoberie striatum a frontálna mozgová kôra, ktoré sa potom prechovávajú pri teplote -70 °C až do okamžiku ich analýzy. Hladiny dopamínu sa merajú veľmi rýchlou kvapalinovou chromatografiou s použitím elektrochemickej detekcie. Štatistické analýzy sa urobia s použitím systému Anova a potom Scheffeovho testu.
Získané výsledky sú uvedené v nasledujúcej tabuľke.
Tabuľka
Hladina dopamínu v pmol/mg v striate (v % vzhľadom ku kontrolným zvieratám)
Hladina dopamínu v pmol/mg vo frontálnej kôre (v % vzhľ. ku kontrolným zvieratám)
| Kontrolná skupina | 876±64 | 2,486±0,290 |
| Zvieratá prijíma- | 219+18 | 1,481+0,180 |
| júce iba MPTP | (-75 %) | (-40 %) |
| Zvieratá ošetrené | 378+39 | 2,359+0,185 |
| riluzolom | (-57 %) | (-5 %) |
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 tvorí aspoň riluzol vo voľnej forme alebo vo forme adičnej soli s farmaceutický prijateľnou kyselinou, v čistom stave alebo vo forme prostriedku, v ktorom je riluzol v kombinácii s ľubovoľným iným farmaceutický zlúčiteľným produktom, ktorý môže byt 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 kapsule, vrecúška) alebo granule. 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 zahrievaním. 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 na požadovanom účinku, dobe liečenia a na použitom spôsobe 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 na veku, hmotnosti a všetkých ostatných charakteristikách liečeného pacienta.
Nasledujúce príklady ilustrujú liečivá podľa vynálezu.
Príklad A
Obvyklou technikou sa pripravia tablety obsahujúce 50 mg účinnej látky s nasledujúcim zložením:
| riluzol | 50 mg |
| manitol | 64 mg |
| mikrokryštalická celulóza | 50 mg |
| polyvidonový excipient | 12 mg |
| nátriumkarboxymetylškrob | 16 mg |
| mastenec | 4 mg |
| stearát horečnatý | 2 mg |
| bezvodná koloidná silika | 2 mg |
zmes metylhydroxypropylcelulózy, polyetylénglykolu 6000 a oxidu titaničitého (72:3,5:24,5)-doplniť na hmotnosť finálnej zapúzdrenej tablety
245 mg.
Príklad B
Obvyklou technikou sa pripravia želatínové tobolky obsahujúce 50 mg účinnej látky s nasledujúcim zložením:
riluzol mg
| celulóza | 18 mg | |
| laktóza | 55 mg | |
| koloidná silika | 1 mg | |
| a | nátriumkarboxymetylškrob | 10 mg |
| mastenec | 10 mg | |
| • | stearát horečnatý | 1 mg. |
Príklad C
Pripraví sa injikovateľný roztok obsahujúci 10 mg účinnej látky s nasledujúcim zložením:
riluzol mg
| kyselina benzoová | 80 mg |
| benzylalkohol | 0,06 cm |
| benzoát sodný | 80 mg |
| etanol (95%) | 0,4 cm3 |
| hydroxid sodný | 24 mg |
| propylénglykol | 1,6 cm3 |
| voda doplniť do | 4 vm3. |
Vynález sa tiež týka spôsobu výroby liečiv použiteľných pri liečení Parkinsonovej choroby a Parkinsonových syndrómov, ktorého podstata spočíva v tom, že sa riluzol alebo farmaceutický prijateľné soli tejto zlúčeniny zmiešajú s jedným alebo niekoľkými farmaceutický prijateľnými riedidlami alebo/a s jednou alebo niekoľkými kompatibilnými a farmaceutický prijateľnými prísadami.
Vynález sa tiež týka spôsobu liečenia cicavca a najmä človeka postihnutého Parkinsonovou chorobou alebo Parkinsonovými syndrómami, ktorého podstata spočíva v tom, že sa podá účinné množstvo riluzolu alebo farmaceutický prijateľných solí tejto zlúčeniny.
Claims (3)
1. Použitie riluzolu alebo farmaceutický prijateľných solí tejto zlúčeniny na výrobu liečiva určeného na liečenie Parkinsonove j choroby a Parkinsonových syndrómov.
Λ •
2. Použitie podľa nároku 1 na získanie liečiva obsahujúce- • ho 25 až 200 mg riluzolu.
3. Spôsob výroby liečiva použiteľného na liečenie Parkinsonove j choroby a Parkinsonových syndrómov, vyznačený tým, že sa riluzol alebo farmaceutický prijateľné soli tejto zlúčeniny zmiešajú s jedným alebo niekoľkými kompatibilnými a farmaceutický prijateľnými riedidlami alebo/a s jednou alebo niekoľkými kompatibilnými a farmaceutický prijateľnými prísadami.
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/FR1994/000003 WO1994015601A1 (fr) | 1993-01-07 | 1994-01-03 | Application du riluzole dans le traitement de la maladie de parkinson et des syndromes parkinsoniens |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK86795A3 true SK86795A3 (en) | 1995-11-08 |
| SK279758B6 SK279758B6 (sk) | 1999-03-12 |
Family
ID=9442862
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK867-95A SK279758B6 (sk) | 1993-01-07 | 1994-01-03 | Parkinsonovejchoroby a parkinsonových syndrómov |
| SK866-95A SK279645B6 (sk) | 1993-01-07 | 1994-01-03 | Použitie karbamazepínu a oxkarbazepínu na prípravu |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK866-95A SK279645B6 (sk) | 1993-01-07 | 1994-01-03 | Použitie karbamazepínu a oxkarbazepínu na prípravu |
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| EP (2) | EP0678026B1 (sk) |
| JP (2) | JPH08505379A (sk) |
| KR (2) | KR100298807B1 (sk) |
| AT (2) | ATE141792T1 (sk) |
| AU (3) | AU677279B2 (sk) |
| CA (2) | CA2153340C (sk) |
| CZ (2) | CZ284928B6 (sk) |
| DE (2) | DE69400799T2 (sk) |
| DK (2) | DK0678023T3 (sk) |
| ES (2) | ES2091689T3 (sk) |
| FR (1) | FR2700117B1 (sk) |
| GR (2) | GR3020975T3 (sk) |
| HU (2) | HU217136B (sk) |
| IL (3) | IL108285A0 (sk) |
| MX (2) | MX9307885A (sk) |
| NO (2) | NO307495B1 (sk) |
| PL (2) | PL309596A1 (sk) |
| RU (1) | RU2221563C2 (sk) |
| SK (2) | SK279758B6 (sk) |
| UA (1) | UA29464C2 (sk) |
| WO (3) | WO1994015610A1 (sk) |
| ZA (3) | ZA9432B (sk) |
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| US6119094A (en) * | 1996-02-29 | 2000-09-12 | Electronic Data Systems Corporation | Automated system for identifying alternate low-cost travel arrangements |
| WO1999034785A2 (en) * | 1998-01-09 | 1999-07-15 | Mor-Research Applications Ltd. | Treatment of dyskinesias |
| US6417210B1 (en) | 1998-01-09 | 2002-07-09 | Mor-Research Applications Ltd. | Treatment of dyskinesias and Parkinson's disease with riluzole and levodopa |
| 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 |
| HUP0303154A3 (en) * | 2001-02-12 | 2009-08-28 | Teva Pharma | New crystal forms of oxcarbazepine and processes for their preparation |
| 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 |
| 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 |
| EP1815849A1 (en) * | 2006-01-31 | 2007-08-08 | Teva Pharmaceutical Industries Ltd | Oxcarbazepine pharmaceutical formulation and its method of preparation, wherein oxcarbazepine has a broad and multi-modal particle size distribution |
| US20070248684A1 (en) * | 2006-01-31 | 2007-10-25 | Sigal Blau | Pharmaceutical formulations of oxcarbazepine and methods for its preparation |
| GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
| ATE496623T1 (de) * | 2006-04-26 | 2011-02-15 | Supernus Pharmaceuticals Inc | Oxcarbazepin-zubereitungen für kontrollierte freisetzung mit sigmoidalem freisetzungsprofil |
| WO2009033715A2 (en) * | 2007-09-14 | 2009-03-19 | Scil Technology Gmbh | Neuroendocrine factors for treatment of degenerative diseases |
| DK3006024T3 (da) | 2009-01-20 | 2019-06-03 | Los Angeles Biomedical Res Inst Harbor Ucla Medical Ct | Benzoesyre eller salte deraf til forstærkning af aktiviteten af et neurofarmaceutisk lægemiddel |
| 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 |
| 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 |
| 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 |
| US9463186B2 (en) | 2013-04-15 | 2016-10-11 | Northwestern University | Treatment for dopaminergic disorders |
| CA3027297A1 (en) | 2016-06-13 | 2017-12-21 | Syneurx International (Taiwan) Corp. | Co-crystals of sodium benzoate and uses thereof |
| RU2022101542A (ru) | 2016-06-13 | 2022-02-03 | Сайньюрекс Интернэшнл (Тайвань) Корп. | Сокристаллы бензоата лития и их применения |
| US10336679B2 (en) | 2016-10-24 | 2019-07-02 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
| US11369579B2 (en) | 2016-10-24 | 2022-06-28 | Syneurx International (Taiwan) Corp. | Polymorphic forms of sodium benzoate and uses thereof |
| WO2018228692A1 (en) * | 2017-06-14 | 2018-12-20 | Birgit Liss | Antagonists of cav2.3 r-type calcium channels for the treatment of neurodegenerative diseases |
| 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 |
| WO2021055890A1 (en) * | 2019-09-20 | 2021-03-25 | Icahn School Of Medicine At Mount Sinai | Controlled release formulations of riluzole and their uses |
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|---|---|---|---|---|
| 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. |
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1994
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