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WO2020122839A2 - Association comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire - Google Patents

Association comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire Download PDF

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Publication number
WO2020122839A2
WO2020122839A2 PCT/TR2019/050960 TR2019050960W WO2020122839A2 WO 2020122839 A2 WO2020122839 A2 WO 2020122839A2 TR 2019050960 W TR2019050960 W TR 2019050960W WO 2020122839 A2 WO2020122839 A2 WO 2020122839A2
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical combination
combination according
tablets
amount
fampridine
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/TR2019/050960
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English (en)
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WO2020122839A3 (fr
Inventor
Ahmet Toksoz
Zafer Toksoz
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 EP19894906.7A priority Critical patent/EP3893855A4/fr
Publication of WO2020122839A2 publication Critical patent/WO2020122839A2/fr
Publication of WO2020122839A3 publication Critical patent/WO2020122839A3/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
    • 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
    • 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
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • 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
    • A61K31/433—Thidiazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
    • 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
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

  • the present invention relates to a pharmaceutical combination comprising a multiple sclerosis agent and at least one muscle relaxant agent wherein the multiple sclerosis agent is teriflunomide or fampridine.
  • 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.
  • MS Multiple sclerosis
  • MS is the most common autoimmune disorder affecting the central nervous system.
  • Multiple sclerosis also known as disseminated sclerosis or encephalomyelitis disseminata
  • MS is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a wide range of signs and symptoms, including physical, mental and sometimes psychiatric problems.
  • MS takes several forms, with new symptoms either occurring in isolated attacks (relapsing forms) or building up over time (progressive forms). Between attacks, symptoms may disappear completely; however, permanent neurological problems often occur, especially as the disease advances.
  • Teriflunomide is a pirimidine synthesis inhibitor. Teriflunomide acts via the mechanism of a dihydroo rotate dehydrogenase inhibitor and it is an orally available immunomodulator used in the treatment of relapsing-remitting multiple sclerosis.
  • the chemical name of teriflunomide is (Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2enamide and its chemical structure is shown in Formula I.
  • Teriflunomide inhibits rapidly dividing cells including activated T cells that are believed to drive the disease process in MS and it may decrease the risk of infection thanks to its more limited effects on the immune system compared to chemotherapeutic agents.
  • EP0527736B1 is the first molecule patent that describes teriflonumide in prior art. It mentions the use of teriflunomide in the prophylaxis and/or treatment of rheumatic diseases and the possibility to administer the pharmaceuticals of the invention orally, topically, rectally and parenterally, if required.
  • Fampridine is a potassium channel blocker indicated for symptomatic improvement of walking in adults with multiple sclerosis, including relapsing remitting, secondary progressive, progressive relapsing and primary progressive.
  • the chemical name of fampridine is 1 ,4- dihydropyridin-4-imine and its chemical structure is shown in Formula II.
  • Muscle relaxants are used to relieve muscle spasms which may result from some conditions which affect the nervous system. Conditions which may cause muscle spasms include multiple sclerosis, motor neuron disease and cerebral palsy. Muscle spasms and tightness may also follow long-term injuries to the head or back. Muscle spasm can also occur as part of a more short-term condition or injury, such as low back pain or whiplash. Medication helps the muscles to relax, which may also reduce pain and discomfort.
  • the muscle relaxant agent is selected from the group comprising tolperisone or tizanidine or baclofen or thiocolchicoside or diazepam or metaxalone or methocarbamol or dantrolene or cyclobenzaprine or carisoprodol or tetrazepam or mixtures thereof.
  • Tolperisone is a centrally acting muscle relaxant that has been used for the symptomatic treatment of spasticity and muscle spasm. It acts as the reticular formation in the brain stem by blocking voltage-gated sodium and calcium channels and it is marketed under trade names including Biocalm, Muscodol, Mydeton, Mydocalm, Mydoflex, Myolax, Myoxan and Viveo.
  • tolperisone 2-methyl-1 -(4-methylphenyl)-3-piperidin-1 -ylpropan-1 - one and its chemical structure is shown in the Formula III.
  • One of the other preferred muscle relaxant agent is tizanidine. Its chemical structure is shown in Formula IV. Formula IV. Tizanidine
  • Tizanidine is a -adrenergic agonist and acts mainly at spinal and supraspinal levels to inhibit excitatory interneurons. It is used for the symptomatic relief of spasticity associated with multiple sclerosis or with spinal cord injury or disease.
  • the recommended dose of tizanidine is 2 mg, 4mg or 6 mg.
  • baclofen Another preferred muscle relaxant agent is baclofen.
  • the chemical name of baclofen is 4- amino-3-(4-chlorophenyl) butanoic acid and is generally represented as follows in Formula V;
  • a further preferred muscle relaxant agent is thiocolchicoside. It is a muscle relaxant with anti- inflammatory and analgesic effects and has been claimed to possess GABA-mimetic and glycinergic actions, in another way we can say that thiocolchicoside is a gamma-aminobutiric acid receptor agonist. Its chemical structure is shown in Formula VI.
  • 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 muscle spasticity.
  • a multiple sclerosis agent especially teriflunomide or fampridine
  • at least one muscle relaxant agent preferably the muscle relaxant agents are tolperisone or tizanidine or baclofen or thiocolchicoside or mixtures thereof.
  • the main object of the present invention is to combine multiple sclerosis agent, teriflunomide or fampridine, with at least one muscle relaxant 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 effective amount of multiple sclerosis agent, teriflunomide or fampridine, and an effective amount of at least one muscle relaxant agent for use in treating a human afflicted with multiple sclerosis, wherein multiple sclerosis agent, teriflunomide or fampridine, and at least one muscle relaxant agent is administered simultaneously, separately or sequentially.
  • tolperisone refers to tolperisone in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • tizanidine refers to tizanidine in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • baclofen refers to baclofen in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • thiocolchicoside refers to thiocolchicoside in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates, esters or mixture thereof.
  • Muscle relaxants are medicines that are used to prevent and reduce muscle spasms and tightness (spasticity). Muscle spasms occur when there is an uncontrolled (involuntary) contraction of a group of muscles. The muscles usually shorten (contract) suddenly; this is often painful. Spasticity occurs when some muscles contract tightly and can then become stiff and harder to use.
  • the pharmaceutical combination comprises teriflunomide or fampridine and at least one muscle relaxant agent.
  • the muscle relaxant agent is selected from the group comprising tolperisone or tizanidine or baclofen or thiocolchicoside or diazepam or metaxalone or methocarbamol or dantrolene or cyclobenzaprine or carisoprodol or tetrazepam or mixtures thereof.
  • the muscle relaxant agent is tolperisone or tizanidine or baclofen or thiocolchicoside or mixtures thereof which is used as adjunctive therapy in pain control and muscle spasticity.
  • one embodiment of this present invention is to combine teriflunomide with tolperisone or tizanidine or baclofen or thiocolchicoside in a same and stable dosage form with desired dissolution profiles.
  • one embodiment of this present invention is to combine fampridine with tolperisone or tizanidine or baclofen or thiocolchicoside in a same and stable dosage form with desired dissolution profiles.
  • This invention provides a method of treating a human afflicted with multiple sclerosis comprising periodical administration of an effective amount of teriflunomide or fampridine and an effective amount of muscle relaxant agent to the subject together, wherein these effective amounts described below are effective to treat a human.
  • the pharmaceutical combination comprises teriflunomide and tolperisone.
  • the pharmaceutical combination comprises teriflunomide in an amount of between 10 mg and 30 mg and tolperisone in an amount of between 20 mg and 200 mg.
  • the weight ratio of teriflunomide to tolperisone is between 0.01 - 4.0, preferably 0.01 -2.0.
  • the pharmaceutical combination comprises teriflunomide and tizanidine.
  • the pharmaceutical combination comprises teriflunomide in an amount of between 10 mg and 30 mg and tizanidine in an amount of between 1 to 10 mg.
  • the weight ratio of teriflunomide to tizanidine is between 1 .0 - 30.0, preferably 2.0 - 10.0, more preferably 3.0 - 8.0.
  • the pharmaceutical combination comprises teriflunomide and baclofen.
  • the pharmaceutical combination comprises teriflunomide in an amount of between 10 mg and 30 mg and baclofen in an amount of between 5 to 20 mg.
  • the weight ratio of teriflunomide to baclofen is between 0.5 - 6.0, preferably 1.0 -2.0.
  • the pharmaceutical combination comprises teriflonomide and thiocolchicoside.
  • the pharmaceutical combination comprises teriflonomide in an amount of between 10 mg to 30 mg and thiocolchicoside in an amount of between 1 to 15 mg.
  • the weight ratio of teriflonomide to thiocolchicoside is between 0.5 - 30.0, preferably 1.0 - 6.0, more preferably 1 .0 - 4.0.
  • the pharmaceutical combination comprises fampridine and tolperisone.
  • the pharmaceutical combination comprises fampridine in an amount of between 5 mg and 20 mg and tolperisone in an amount of between 20 mg and 200 mg.
  • the weight ratio of fampridine to tolperisone is between 0.01 - 4.0, preferably 0.01 -1.0.
  • the pharmaceutical combination comprises fampridine and tizanidine.
  • the pharmaceutical combination comprises fampridine in an amount of between 5 mg and 20 mg and tizanidine in an amount of between 1 to 10 mg.
  • the weight ratio of fampridine to tizanidine is between 0.5 - 20.0, preferably 2.0 - 10.0, more preferably 2.0 -7.0.
  • the pharmaceutical combination comprises fampridine and baclofen.
  • the pharmaceutical combination comprises fampridine in an amount of between 5 mg and 20 mg and baclofen in an amount of between 5 to 20 mg.
  • the weight ratio of fampridine to baclofen is between 0.25 - 4.0, preferably 0.5 - 2.0.
  • the pharmaceutical combination comprises fampridine and thiocolchicoside.
  • the pharmaceutical combination comprises fampridine in an amount of between 5 mg to 20 mg and thiocolchicoside in an amount of between 1 to 15 mg.
  • the weight ratio of fampridine to thiocolchicoside is between 0.1 - 20.0, preferably 1.0 - 5.0, preferably 1.0 - 3.0.
  • 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, colouring 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, colouring 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, poloxamer 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 colouring 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; low substituted 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 a capsule.
  • the 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 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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Abstract

La présente invention concerne une association pharmaceutique comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire, l'agent contre la sclérose en plaques étant le tériflunomide ou la fampridine.
PCT/TR2019/050960 2018-12-12 2019-11-15 Association comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire Ceased WO2020122839A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19894906.7A EP3893855A4 (fr) 2018-12-12 2019-11-15 Association comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2018/19202A TR201819202A2 (tr) 2018-12-12 2018-12-12 Bi̇r multi̇pl skleroz ajani ve en az bi̇r kas relaksan ajan i̇çeren bi̇r kombi̇nasyon
TR2018/19202 2018-12-12

Publications (2)

Publication Number Publication Date
WO2020122839A2 true WO2020122839A2 (fr) 2020-06-18
WO2020122839A3 WO2020122839A3 (fr) 2021-02-18

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PCT/TR2019/050960 Ceased WO2020122839A2 (fr) 2018-12-12 2019-11-15 Association comprenant un agent contre la sclérose en plaques et au moins un agent relaxant musculaire

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EP (1) EP3893855A4 (fr)
TR (1) TR201819202A2 (fr)
WO (1) WO2020122839A2 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016073510A1 (fr) 2014-11-04 2016-05-12 Adamas Pharmaceuticals, Inc. Méthodes d'administration de compositions d'amantadine

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* Cited by examiner, † Cited by third party
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