WO2019245512A2 - Combinaison comprenant du fingolimod et au moins un agent anti-épileptique - Google Patents

Combinaison comprenant du fingolimod et au moins un agent anti-épileptique Download PDF

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Publication number
WO2019245512A2
WO2019245512A2 PCT/TR2019/050471 TR2019050471W WO2019245512A2 WO 2019245512 A2 WO2019245512 A2 WO 2019245512A2 TR 2019050471 W TR2019050471 W TR 2019050471W WO 2019245512 A2 WO2019245512 A2 WO 2019245512A2
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical combination
tablets
combination according
fingolimod
gabapentin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/TR2019/050471
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English (en)
Other versions
WO2019245512A3 (fr
Inventor
Ali Turkyilmaz
Merve PEKER
Emine TUNCAY
Erkin Ozturk
Muge ULUSOY BOZYEL
Yavuz Dedeoglu
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.)
Sanovel Ilac Sanayi ve Ticaret AS
Original Assignee
Sanovel Ilac Sanayi ve Ticaret AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanovel Ilac Sanayi ve Ticaret AS filed Critical Sanovel Ilac Sanayi ve Ticaret AS
Priority to EP19822106.1A priority Critical patent/EP3810274A4/fr
Publication of WO2019245512A2 publication Critical patent/WO2019245512A2/fr
Publication of WO2019245512A3 publication Critical patent/WO2019245512A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the present invention relates to a pharmaceutical combination comprising fingolimod or a pharmaceutically acceptable salt thereof and at least one anti-epileptic agent.
  • MS Multiple Sclerosis
  • CNS central nervous system
  • Myelin provides a covering or insulation for nerves, improves the conduction of impulses along the nerves and also is important for maintaining the health of the nerves.
  • inflammation causes the myelin to disappear. So, the electrical impulses become slower.
  • the nerves themselves are damaged. Patient suffers from a range of symptoms which affect their health-related quality of life such as pain, muscle spasticity and spasm, bladder problems and sleep disturbance.
  • Fingolimod is a sphingosine-1 -phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. Fingolimod is used in the treatment of the relapsing form of multiple sclerosis. May also be used in chronic inflammatory demyelinating polyneuropathy.
  • Fingolimod is marketed by Novartis under the brand name Gilenya® for the treatment of multiple sclerosis.
  • Gilenya® is presented as immediate-release hard gelatin capsules containing 0.56 mg of fingolimod hydrochloride as the active substance corresponding to 0.5 mg of fingolimod.
  • fingolimod 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1 ,3-diol. Fingolimod is shown as Formula I.
  • fingolimod derivatives are firstly disclosed in US5604229.
  • the use of fingolimod derivatives as immune depressant and a preventive or remedy for autoimmune diseases is disclosed in EP0627406 (B1).
  • the use of fingolimod derivatives in the prevention or treatment of chronic rejection in a recipient of organ or tissue alio- or xeno-transplant is disclosed in EP0941082 (B1).
  • the strategy to improve the current state of MS treatment is to combine therapies.
  • fingolimod with at least one anti-epileptic agent, in the prior art.
  • Anti-epileptic agents are the main type of treatment for most people with epilepsy.
  • the treatment of epilepsy generally is directed toward reducing the frequency of seizures.
  • An accurate diagnosis of the form of epilepsy is critical to selection of the drug most likely to be effective.
  • the medicaments currently used for the prevention and/or treatment of epilepsy are fundamentally based on (voltage and neuronal receptor-associated) ion channel inhibitor compounds.
  • the anti-epileptic agents are selected from the group comprising gabapentin or pregabalin or phenytoin or phenobarbital or carbamazepine or oxcarbazepine or stiripentol or eslicarbazepine acetate or paramethadione or brivaracetam or etiracetam or levetiracetam or seletracetam or progabide or tiagabine or valproate or vigabatrin or combinations thereof .
  • gabapentin l-(aminomethyl)-cyclohexaneocetic acid
  • Formula II Formula II
  • Gabapentin was designed as a GABA analog that would cross the blood-brain barrier. Gabapentin was found to have anticonvulsant and anti-spastic activity with extremely low toxicity in human. Gabapentin is presently marketed under the trademark Neurontin as adjunctive therapy in the treatment of partial seizures in patients with epilepsy.
  • pregabalin which is an analog of gamma-aminobutyric acid (GABA). Its chemical designation is (S)-3-(aminomethyl)-5-methyl hexanoic acid, with the chemical structure illustrated below with Formula III.
  • pregabalin binds to the auxiliary sub-unit of voltage-sensitive calcium channels in the central nervous system, thereby replacing the [3H]-gabapentin. It also reduces the release of many neurotransmitters, including pregabalin glutamate, noradrenaline and the substance P. It is used for the treatment of epilepsy, simple or complex partial convulsion, either accompanied or not by secondary generalized convulsions, and of neuropathic pain.
  • combining more than one molecule in one dosage form increases the patient’s compliance.
  • this combination increases the patients’ quality of life, combining more than one molecule in one dosage form also reduces undesired multiple sclerosis symptoms which can be pain.
  • the antiepileptic agents are gabapentin or pregabalin or mixtures thereof.
  • the main object of the present invention is to combine fingolimod with at least one anti epileptic agent to eliminate multiple sclerosis symptoms, to provide rapid and effective treatment and to bring additional advantages over the relevant prior art.
  • Another object of the present invention is to obtain a stable combination formulation with synergistic effect for use in multiple sclerosis.
  • This invention also provides a pharmaceutical combination comprising an amount of fingolimod and an amount of an anti-epileptic agent, especially gabapentin or pregabalin, for use in treating a human afflicted with multiple sclerosis, wherein fingolimod and an anti epileptic agent are administered simultaneously, separately or sequentially.
  • an anti-epileptic agent especially gabapentin or pregabalin
  • fingolimod refers to fingolimod in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • gabapentin refers to gabapentin in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • pregabalin refers to pregabalin in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • the pharmaceutical combination comprises fingolimod and at least one anti-epileptic agent.
  • the anti-epileptic agent is selected from the group comprising gabapentin or pregabalin or phenytoin or phenobarbital or carbamazepine or oxcarbazepine or stiripentol or eslicarbazepine acetate or paramethadione or brivaracetam or etiracetam or levetiracetam or seletracetam or progabide or tiagabine or valproate or vigabatrin or combinations thereof.
  • the anti-epileptic agent is gabapentin or pregabalin or combinations thereof which is used as adjunctive therapy in pain control.
  • an embodiment of this present invention is to combine fingolimod with gabapentin or pregabalin in a same and stable dosage form with desired dissolution profiles.
  • the pharmaceutical combination comprises fingolimod and gabapentin.
  • This invention provides a method of treating a human afflicted with multiple sclerosis comprising periodical administration of an amount of fingolimod and an amount of anti epileptic agent to the subject together, wherein these amounts described below are effective to treat a human.
  • the pharmaceutical combination comprises fingolimod in an amount of between 0.05 and 20 mg and gabapentin in an amount of between 100 and 400 mg.
  • the weight ratio of fingolimod to gabapentin is between 0.000125 - 2.0, preferably 0.001 -1.0, preferably 0.001 - 0.2.
  • the pharmaceutical combination comprises fingolimod and pregabalin.
  • the pharmaceutical combination comprises fingolimod in an amount of between 0.05 to 20 mg and pregabalin in an amount of between 80 to 200 mg.
  • the weight ratio of fingolimod to pregabalin is between 0.0001 - 2.0, preferably 0.001 -1.0, more preferably 0.001 - 0.25.
  • said combination further comprises at least one pharmaceutically acceptable excipient which is selected from fillers, binders, disintegrants, solvents and co-solvents, rate controlling polymers, direct compression agent, surfactants, lubricants, glidants, sweeteners, stabilizers, coating agents, coloring agents, inert agents or mixtures thereof.
  • at least one pharmaceutically acceptable excipient which is selected from fillers, binders, disintegrants, solvents and co-solvents, rate controlling polymers, direct compression agent, surfactants, lubricants, glidants, sweeteners, stabilizers, coating agents, coloring agents, inert agents or mixtures thereof.
  • Suitable fillers are selected from the group comprising microcrystalline cellulose, mannitol, spray-dried mannitol, lactose, lactose monohydrate, starch, dextrose, sucrose, fructose, maltose, sorbitol, xylitol, inositol, kaolin, inorganic salts, calcium salts, polysaccharides, dicalcium phosphate, sodium chloride, dextrates, lactitol, maltodextrin, sucrose-maltodextrin mixture, trehalose, sodium carbonate, sodium bicarbonate, calcium carbonate or mixtures thereof.
  • Suitable binders are selected from the group comprising polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, starch, pregelatinized starch, glucose, glucose syrup, natural gums, sucrose, sodium alginate, cellulose derivatives such as hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxy methyl cellulose, methyl cellulose, gelatin, carrageenan, guar gum, carbomer, polymethacrylates, methacrylate polymers, collagens, proteins like gelatin, agar, alginate, alginic acid, xanthan gum, hyaluronic acid, pectin, polysaccharides, carbomer, poloxamer, polyacrylamide, aluminium hydroxide, laponit, bentonit, polyoxyethylene-alkyl ether, polydextrose, polyethylene oxide or mixtures thereof.
  • Suitable disintegrants are selected from the group comprising polyvinil pyrrolidone (crospovidone), povidone, cross-linked carboxymethyl cellulose (croscarmellose sodium), low-substituted hydroxypropyl cellulose, pregelatinized starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, docusate sodium, guar gum, low substituted hydroxypropyl cellulose, polyacryline potassium, sodium alginate, corn starch, sodium starch glycolate, alginic acid, alginates, ion-exchange resins, magnesium aluminium silica, sodium dodesyl sulphate, poloxamer, sodium glycine carbonate, sodium lauryl sulphate or mixtures thereof.
  • polyvinil pyrrolidone crospovidone
  • povidone povidone
  • croscarmellose sodium cross-linked carboxymethyl cellulose
  • low-substituted hydroxypropyl cellulose pregelatinized
  • Suitable solvents or co-solvents are selected from the group comprising water, propylene glycol, glycerin, ethanol, polyethylene glycol or mixtures thereof.
  • Suitable rate controlling polymers are selected from the group comprising ethyl acrylate, ethyl methacrylate copolymer, ethylcellulose, methylcellulose, hypromellose phthalate, polydextrose, polyvinylacetate phthalate, zein, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose E4M, hydroxypropyl methylcellulose K100MCR, hydroxyethyl cellulose, hydroxymethyl cellulose, gelatin, polyethylene oxide, acacia, dextrin, starch, polyhydroxyethylmethacrylate, sodium carboxymethylcellulose, carboxymethyl cellulose, sodium alginate, alginic acid, pectin, polyglucoronic acid, polygalacturonic acid, chondroitic sulfate, carrageenan, lambda carregeenan, io
  • Suitable direct compression agents are selected from the group comprising calcium hydrogen phosphate sodium alginate, pregelatinized starch, calcium citrate or mixtures thereof.
  • Suitable surfactants are selected from the group comprising sodium docusate, glyceryl monooleate, polyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, sorbic acid, sorbitan fatty acid ester, nonoxynol, polyoxyethylene stearates, polyethylene glycol, leucine, polaxomer 407, sodium benzoate, docusate sodium, alpha tocopherol, ascorbyl palmitate, citric acid, polyethoxylated fatty acid esters, polyoxyethylene hydrogenated castor oil or mixtures thereof.
  • Suitable lubricants are selected from the group comprising from magnesium stearate, colloidal silicon dioxide, calcium stearate, zinc stearate, talc, waxes, boric acid, hydrogenated vegetable oil, sodium chlorate, magnesium lauryl sulfate, sodium oleate, sodium acetate, sodium benzoate, polyethylene glycol, stearic acid, fatty acid, fumaric acid, glyseryl palmito sulphate, sodium stearyl fumarate, sodium lauryl sulphate or mixtures thereof.
  • Suitable glidants are selected from the group comprising colloidal silicon dioxide, corn starch, talc or mixtures thereof.
  • Suitable sweeteners are selected from the group comprising aspartame, potassium acesulfame, sodium saccharinate, neohesperidine dihydrochalcone, sucralose, saccharin, sugars such as sucrose, glucose, lactose, fructose or sugar alcohols such as mannitol, sorbitol, xylitol, erythritol or mixtures thereof.
  • Suitable stabilizers are selected from the group comprising citric acid, fumaric acid, tartaric acid, sodium citrate, sodium benzoate, sodium dihydrogen phosphate, calcium carbonate, magnesium carbonate, arginine, lysine, meglamine, ascorbic acid, gallic acid esters or the mixtures thereof, and preferably, citric acid, fumaric acid, arginine or mixtures thereof.
  • Suitable coating agents are selected from the group comprising polymethacrylates, polyalkylacrylates copolymers, hydroxyl propyl methyl cellulose, lactose monohydrate, hydroxypropyl cellulose, polyvinyl alcohol, polyethylene glycol, talc, polyvinyl alcohol- polyethylene glycol copolymers (Kollicoat® IR), ethylcellulose dispersions (Surelease®), polyvinylprolidone, polyvinylprolidone-vinyl acetate copolymer (PVP-VA), all kinds of Opadry®, pigments, dyes, titanium dioxide, iron oxide or mixtures thereof.
  • Suitable coloring agents are selected from the group comprising ferric oxide, titanium dioxide, Food, Drug & Cosmetic (FD&C) dyes (such as; FD&C blue, FD&C green, FD&C red, FD&C yellow, FD&C lakes), poncau, indigo Drug & Cosmetic (D&C) blue, indigotine FD&C blue, carmoisine indigotine (indigo Carmine); iron oxides (such as; iron oxide red, yellow, black), quinoline yellow, flaming red, carmine, carmoisine, sunset yellow or mixtures thereof.
  • FD&C Food, Drug & Cosmetic
  • Suitable inert agents between the two molecules are selected from starch, lactose, sugar alcohol like D-mannitol, erythritol; lowsubstituted hydroxypropyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, methylcellulose, hydroxyethyl methylcellulose or mixtures thereof.
  • the pharmaceutical combination is administered orally.
  • the pharmaceutical combination is in the form of tablets, capsules, strips, syrups, powders, pastilles, sachets, effervescent compositions, pills, coated bead systems, granules, microspheres, dragees, films, orally administrable films, solutions, solids, suspensions or emulsions.
  • the pharmaceutical combination is in the form of tablets or capsules.
  • the pharmaceutical combination is in the form of a tablet.
  • the pharmaceutical combination is formulated as tablets comprising film-coated tablets, bilayer tablets, inlay tablets, orally disintegrating tablets, compressed tablets, coated or uncoated tablets, multilayer tablets, mini tablets, buccal tablets, sublingual tablets, effervescent tablets, gastric disintegrating tablets, chewable tablets, dispersing tablets or lozenges.
  • the pharmaceutical combination is in the form of tablets or capsules.
  • the pharmaceutical combination is in the form of a capsule.
  • the pharmaceutical combination further comprises a vitamin.
  • the said vitamin is selected from the group comprising vitamin A, vitamin B1 , vitamin B2, vitamin B3, vitamin B4, vitamin B5, vitamin B6, vitamin B7, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K.
  • the vitamin is cobalamin (vitamin B12).
  • the pharmaceutical combination comprises vitamin B12 in an amount of between 0.05 to 10 mg.
  • the pharmaceutical combination comprises fingolimod and gabapentin wherein the dosage form of this combination provides immediate release.
  • modified release dosage form is selected from the group comprising controlled release, sustained release, delayed release, extended release, repeat action system or mixtures thereof.
  • modified release dosage form is prepared using rate controlling polymers.
  • the pharmaceutical combination comprises fingolimod and pregabalin wherein the combination provides both immediate release and modified release.
  • the combination may comprise vitamin B12.
  • the pharmaceutical combination subjected to the invention is composed of at least two parts wherein at least one part provides modified and at least one part provides immediate release in an oral administration.
  • the combination is prepared using direct compression, wet or dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion, spheronization, slugging, spray drying or solvent evaporation.
  • the combination is for use in the treatment of multiple sclerosis in human.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une combinaison pharmaceutique comprenant du fingolimod ou un sel pharmaceutiquement acceptable de celui-ci et au moins un agent anti-épileptique.
PCT/TR2019/050471 2018-06-21 2019-06-19 Combinaison comprenant du fingolimod et au moins un agent anti-épileptique Ceased WO2019245512A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19822106.1A EP3810274A4 (fr) 2018-06-21 2019-06-19 Combinaison comprenant du fingolimod et au moins un agent anti-épileptique

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2018/08815 2018-06-21
TR201808815 2018-06-21

Publications (2)

Publication Number Publication Date
WO2019245512A2 true WO2019245512A2 (fr) 2019-12-26
WO2019245512A3 WO2019245512A3 (fr) 2020-06-04

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PCT/TR2019/050471 Ceased WO2019245512A2 (fr) 2018-06-21 2019-06-19 Combinaison comprenant du fingolimod et au moins un agent anti-épileptique

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EP (1) EP3810274A4 (fr)
WO (1) WO2019245512A2 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018082814A1 (fr) 2016-11-07 2018-05-11 Metriopharm Ag Utilisation de 5-amino-2,3-dihydro-1,4-phthalazinedione dans le traitement de la sclérose en plaques progressive chronique

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PE20100371A1 (es) * 2008-10-31 2010-06-01 Lexicon Pharmaceuticals Inc Agonistas del receptor s1p para el tratamiento de malaria cerebral
US20140308244A1 (en) * 2011-08-08 2014-10-16 The Board Of Trustees Of The Leland Stanford Junior University Combination Therapy for Treatment of Inflammatory Demyelinating Disease
WO2013190151A1 (fr) * 2013-05-13 2013-12-27 Synthon B.V. Composition pharmaceutique contenant du fingolimod

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018082814A1 (fr) 2016-11-07 2018-05-11 Metriopharm Ag Utilisation de 5-amino-2,3-dihydro-1,4-phthalazinedione dans le traitement de la sclérose en plaques progressive chronique

Also Published As

Publication number Publication date
EP3810274A2 (fr) 2021-04-28
WO2019245512A3 (fr) 2020-06-04
EP3810274A4 (fr) 2022-03-16

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