WO2012147099A1 - Compositions pharmaceutiques de lévodopa, de carbidopa et d'entacapone - Google Patents

Compositions pharmaceutiques de lévodopa, de carbidopa et d'entacapone Download PDF

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Publication number
WO2012147099A1
WO2012147099A1 PCT/IN2012/000276 IN2012000276W WO2012147099A1 WO 2012147099 A1 WO2012147099 A1 WO 2012147099A1 IN 2012000276 W IN2012000276 W IN 2012000276W WO 2012147099 A1 WO2012147099 A1 WO 2012147099A1
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WO
WIPO (PCT)
Prior art keywords
entacapone
levodopa
carbidopa
pharmaceutically acceptable
hydrates
Prior art date
Application number
PCT/IN2012/000276
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English (en)
Inventor
Ravula Sayisiva Prasad
Original Assignee
Suven Nishtaa Pharma Pvt. Ltd.
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 Suven Nishtaa Pharma Pvt. Ltd. filed Critical Suven Nishtaa Pharma Pvt. Ltd.
Publication of WO2012147099A1 publication Critical patent/WO2012147099A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic 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
    • A61K31/198Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/275Nitriles; Isonitriles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2072Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/28Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806Coating materials
    • A61K9/2833Organic macromolecular compounds
    • A61K9/286Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs

Definitions

  • the present invention relates to the pharmaceutical composition
  • the pharmaceutical composition comprising Levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof and the process for preparing the same.
  • Levodopa an aromatic amino acid
  • Carbidopa an inhibitor of aromatic amino acid decarboxylation
  • Carbidopa is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (-)-L-(a-hydrazino-(a-methyl-P-(3,4-dihydroxybenzene) propanoic acid monohydrate. Its empirical formula is Ci 0 Hl 4 N 2 O 4 H 2 O, and its structural formula is
  • Levodopa and carbidopa are most commonly used drugs in the treatment of the Parkinson's disease.
  • Levodopa and carbidopa are commercially available as a combination with the trade name SINMET in the dosage form of tablets and marketed by Merck Sharp & Dohme limited in UK.
  • Entacapone an inhibitor of catechol-O-methyltransferase (COMT)
  • COMT catechol-O-methyltransferase
  • the chemical name of entacapone is (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2- propenamide. Its empirical formula is C 14H15N3O5 and its structural formula is
  • Entacapone is described in the European patent EP0444899 Bl as a Catechol-O- methyl- transferase (COMT) inhibitor.
  • the publication further discloses that for the treatment of the Parkinson's disease, entacapone is given with levodopa, in each of its own composition or combined in one composition.
  • the European patent EP1 1 12065 B 1 describes an oral compacted composition comprising a pharmaceutically effective amount of entacapone or a pharmaceutically acceptable salt thereof and a croslinked cellulose derivative.
  • Entacapone is commercially available with the trade name COMTESS in the dosage form of film coated tablets and marketed by Orion Corporation in UK.
  • European Patent EP 1 189608 Bl discloses an oral solid pharmaceutical composition comprising levodopa, carbidopa and entacapone or their pharmaceutically acceptable salts or hydrates thereof wherein the substantial portion of the carbidopa or pharmaceutically acceptable salt or hydrates thereof is separated from entacapone and levodopa or pharmaceutically acceptable salts or hydrates thereof in the tablet.
  • the applicants of this patent further states that it is very difficult to adjust the absorption of the three different active agents from one and the same oral solid composition.
  • WO2008053297 A2 describes the single oral composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts thereof, where in substantial portion of entacapone or a pharmaceutically acceptable salt or hydrate thereof is separated from the mixture of levodopa and carbidopa or pharmaceutically acceptable salts or hydrates thereof.
  • the present formulation poses a challenge to the formulator to formulate the dosage form comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof as the three active ingredients are highly desirable to be released from the oral solid composition , in a manner so as to achieve the targeted ranges of the pharmacokinetic parameters which in turn would ensure optimal therapeutic activity. It is very challenging to achieve the absorption of the three active ingredients to the therapeutic concentration. It is essential to achieve the desired dissolution profile in different pH media to get the desired absorption. So there is a need to develop a stable solid pharmaceutical composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates in order to achieve the desired release of the three active ingredients.
  • the present invention relates to pharmaceutical composition
  • pharmaceutical composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof and process for preparing the same.
  • the Present invention relates to the pharmaceutical composition comprising two discrete portions of the mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof.
  • the invention relates to a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the first discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules and the second discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the powder.
  • the invention relates to a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the first discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules and the second discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules.
  • the invention provides a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the ratio of mixtures levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof in the first discrete portion to the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof present in the second discrete portion is in the range of 0.01 : 1 to 1 :0.01.
  • the present invention relates to a process for the preparation of the pharmaceutical composition comprising two discrete portions of mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the said process comprises a) wet granulating the first discrete portion of mixture comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof with atleast one pharmaceutically excipients with a binder solution to form granules, b) drying and optionally milling said granules, c) mixing said granules with the second discrete portion of the mixture comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof and atleast one pharmaceutically excipients to form a blend, d) lubricating said blend with atleast one lubricant to form a final blend e) Compressing said final blend to form a tablet
  • the present invention further relates to a process of the pharmaceutical composition comprising two discrete portions of mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the said process comprises a) wet granulating the first discrete portion of the mixture of levodopa, carbidopa and entacapone or pharmaceutical salts thereof or hydrates thereof with atleast one pharmaceutically acceptable excipient with a binder solution to form granules, b) wet granulating the second discrete portion of the mixture of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof with atleast one pharmaceutically acceptable excipient with a binder solution to form the granules, c) mixing the granules of the first discrete portion granules and second discrete portion granules of step no a and b, d) lubricating the above mixture with
  • the present invention relates to pharmaceutical composition
  • pharmaceutical composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof and process for preparing the same.
  • discrete portion refers to a quantity of the mixture of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof being separated from the other mixture of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof.
  • the present invention relates to the pharmaceutical composition comprising two discrete portions of the mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof.
  • the invention relates to a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the first discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules and the second discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the powder.
  • the invention relates to a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the first discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules and the second discrete portion of the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is in the form of the granules.
  • the invention provides a pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the ratio of mixtures levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof in the first discrete portion to the mixture of the levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof present in the second discrete portion is in the range of 0.01 : 1 to 1 :0.01.
  • the stabilizer useful in the pharmaceutical composition of the present invention is acidic substance or alkaline substance or mixtures thereof.
  • the acidic substances used as the stabilizers in the stable pharmaceutical composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is selected from the group consisting of citric acid, tartaric acid, malic acid and mixtures thereof. Out of these citric acid is most preferred acidic substance used as a stabilizer.
  • the alkaline substances used as the stabilizers the stable pharmaceutical composition comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof is selected from the group consisting of sodium carbonate, ammonium carbonate, anhydrous sodium carbonate, sodium carbonate monohydrate, sodium tartrate, sodium potassium tartrate, sodium citrate, sodium hydroxide, calcium acetate, sodium acetate, dibasic sodium phosphate, anhydrous dibasic sodium phosphate, di ammonium hydrogen phosphate, sodium pyrophosphate and mixtures thereof.
  • di basic sodium phosphate, sodium citrate, ammonium carbonate and the mixtures thereof are most preferred alkaline substances used as a stabilizer.
  • the pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof preferably contains the stabilizer from 0.5% to 10% by .weight of the total solid dosage form. Most preferably, the composition contains the stabilizer from 1 to 5% by weight of the total solid dosage form (e.g. 1 to 5% of the total tablet weight).
  • the stabilizer is present in the first discrete portion of the pharmaceutical composition of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof.
  • suitable fillers may include one or more of the microcrystalline cellulose and dibasic calcium phosphate.
  • the filler used in the stable pharmaceutical composition of levodopa, carbidopa, and entacapone or pharmaceutically acceptable salts or hydrates thereof is microcrystalline cellulose.
  • the microcrystalline cellulose is present in the range from about 5%. to 50% w/w of the total pharmaceutical composition. Most preferably the microcrystalline cellulose may be present in the range from about 10% to 30% w/w of the total pharmaceutical composition.
  • Microcrystalline cellulose is present both in the first and second discrete portion preferably in the range in the range of 4: 1 and more preferably in the range of 3 : 1.
  • Suitable binders may include one or more of povidone, starch, stearic acid, gums, hydroxy propyl methyl cellulose and the like.
  • Suitable lubricants may include one or more of magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oil and the like.
  • Suitable disintegrants may include one or more of crospovidone, sodium starch glycolate and Amberlite I P-88.
  • the present invention relates to a process for the preparation of the pharmaceutical composition comprising two discrete portions of mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the said process comprises a) wet granulating the first discrete portion of mixture comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof with atleast one pharmaceutically excipients with a binder solution to form granules, b) drying and optionally milling said granules, c) mixing said ⁇ granules with the second discrete portion of the mixture comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof and atleast one pharmaceutically excipients to form a blend, d)
  • the present invention further relates to a process of the pharmaceutical composition comprising two discrete portions of mixtures of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof wherein the said process comprises a) wet granulating the first discrete portion of the mixture of levodopa, carbidopa and entacapone or pharmaceutical salts thereof or hydrates thereof with atleast one pharmaceutically acceptable excipient with a binder solution to form granules, b) wet granulating the second discrete portion of the mixture of levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof with atleast one pharmaceutically acceptable excipient with a binder solution to form the granules, c) mixing the granules of the first discrete portion granules and second discrete portion granules of step no a and b, d) lubricating the above mixture with
  • Table- 1 provides the composition of the tablet comprising levodopa, carbidopa and entacapone or pharmaceutically acceptable salts or hydrates thereof where all the active ingredients are wet granulated at the same time and compacted into the tablets
  • the pharmaceutical composition is prepared by mixing the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone with the microcrystalline cellulose, citric acid, aerosil in ' a double cone blender.
  • the blended mixture is wet granulated with the binder solution comprising the hydroxypropyl methyl cellulose in isopropyl alchol and dichloro methane in the rapid mixture granulator.
  • the granules are dried in the tray dryer and milled through the sieve #40.
  • the granules prepared are mixed with the second discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone, microcrystalline cellulose, crospovidone in a double cone blender and lubricated with magnesium stearate.
  • the lubricated blend is compressed into the tablets and further film coated with the film coating solution.
  • Table-3 provides the composition of the present invention Table-3
  • the pharmaceutical composition is prepared by mixing the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone with the microcrystalline cellulose, citric acid, aerosil in a double cone blender.
  • the blended mixture is wet granulated with the binder solution comprising the hydroxypropyl methyl cellulose in purified water in the rapid mixture granulator.
  • the granules are dried in the tray dryer and milled through the sieve #40.
  • the granules prepared are mixed with the second discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone, microcrystalline cellulose, crospovidone in a double cone blender and lubricated with magnesium stearate.
  • the lubricated blend is compressed into the tablets and further film coated with the film coating solution.
  • the pharmaceutical composition is prepared by mixing the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone with the microcrystalline cellulose, citric acid, aerosil in a double cone blender.
  • the blended mixture is wet granulated with the binder solution comprising the hydroxypropyl methyl cellulose in isopropyl alchol and dichloro methane in the rapid mixture granulator to form the granules of the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone.
  • the granules of the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone are dried in the tray dryer and milled through the sieve #40.
  • the second discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone with the microcrystalline cellulose and crospovidone is wet granulated with the binder solution comprising the hydroxy propyl methyl cellulose in isopropyl alchol and dichloro methane in the rapid mixture granulator to form the granules of the second discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone.
  • the granules of the second discrete portion of the mixture levodopa, carbidopa monohydrate and levodopa are dried in the tray dryer and milled through sieve #60.
  • the granules comprising the first discrete portion of the mixture of levodopa, carbidopa monohydrate and entacapone and the granules comprising the second discrete portion of the mixture of the mixture of levodopa, carbidopa monohydrate and entacapone are mixed in the double cone blender and lubricated with the magnesium stearate to form the lubricated blend.
  • the above lubricated blend is compressed into the tablets and further film coated with the film coating solution.
  • CD Carbidopa

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Abstract

La présente invention concerne une composition pharmaceutique comprenant deux parties distinctes de mélanges de lévodopa, de carbidopa et d'entacapone ou de leurs sels ou leurs hydrates pharmaceutiquement acceptables. L'invention porte en outre sur le procédé de préparation de ladite composition.
PCT/IN2012/000276 2011-04-25 2012-04-17 Compositions pharmaceutiques de lévodopa, de carbidopa et d'entacapone WO2012147099A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN168/CHE/2011 2011-04-25
IN3559/CHE/2010 2011-04-25
IN168CH2011 2011-04-25
IN3559CH2010 2011-04-25

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WO2012147099A1 true WO2012147099A1 (fr) 2012-11-01

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016036308A1 (fr) 2014-09-04 2016-03-10 Lobsor Pharmaceuticals Aktiebolag Compositions pharmaceutiques comprenant de la lévodopa, un inhibiteur de la dopamine décarboxylase et un inhibiteur de la comt, et leur procédé d'administration
WO2019182506A1 (fr) 2018-03-23 2019-09-26 Lobsor Pharmaceuticals Aktiebolag Administration continue d'une composition pharmaceutique pour le traitement de troubles neurodégénératifs
US10555922B2 (en) 2015-09-04 2020-02-11 Lobsor Pharmaceuticals Aktiebolag Method of treating a dopamine related disorder in a subject by administering levodopa, in combination with a dopamine decarboxylase inhibitor and a catechol-o-methyltransferase inhibitor

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EP0444899B1 (fr) 1990-02-27 1997-02-05 Orion-Yhtymà„ Oy Dérivés du catéchol, ses sels, esters physiologiquement acceptables et leur utilisation pour le traitement du dammage du tissu induit par la peroxidation de la graisse
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EP1112065A1 (fr) 1998-09-14 2001-07-04 Orion Corporation Composition pharmaceutique comprenant une entacapone ou nitecapone, de meme qu'un derive de cellulose reticule
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WO2008053297A2 (fr) 2006-10-30 2008-05-08 Wockhardt Research Centre Compositions pharmaceutiques comprenant l'entacapone, la lévodopa, et la carbidopa
US20080118556A1 (en) * 1998-11-02 2008-05-22 Elan Corporation, Plc Modified Release of Compositions Containing a Combination of Carbidopa, Levodopa and Entacapone
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WO2011107653A2 (fr) * 2010-03-04 2011-09-09 Orion Corporation Méthode de traitement de la maladie de parkinson

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EP1112065A1 (fr) 1998-09-14 2001-07-04 Orion Corporation Composition pharmaceutique comprenant une entacapone ou nitecapone, de meme qu'un derive de cellulose reticule
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WO2008053297A2 (fr) 2006-10-30 2008-05-08 Wockhardt Research Centre Compositions pharmaceutiques comprenant l'entacapone, la lévodopa, et la carbidopa
WO2010020969A1 (fr) * 2008-08-22 2010-02-25 Wockhardt Research Centre Composition pharmaceutique à libération prolongée d’entacapone ou de sels correspondants
WO2011107653A2 (fr) * 2010-03-04 2011-09-09 Orion Corporation Méthode de traitement de la maladie de parkinson

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016036308A1 (fr) 2014-09-04 2016-03-10 Lobsor Pharmaceuticals Aktiebolag Compositions pharmaceutiques comprenant de la lévodopa, un inhibiteur de la dopamine décarboxylase et un inhibiteur de la comt, et leur procédé d'administration
US10071069B2 (en) 2014-09-04 2018-09-11 Lobsor Pharmaceuticals Aktiebolag Pharmaceutical compositions comprising levodopa, a dopamine decarboxylase inhibitor and a COMT inhibitor and method of administration thereof
US10786472B2 (en) 2014-09-04 2020-09-29 Lobsor Pharmaceuticals Aktiebolag Pharmaceutical compositions comprising levodopa, a dopamine decarboxylase inhibitor and a COMT inhibitor and method of administration thereof
EP3782617A1 (fr) 2014-09-04 2021-02-24 LobSor Pharmaceuticals Aktiebolag Compositions pharmaceutiques sous forme de gel comprenant de la lévodopa, carbidopa et entacapone
US11413262B2 (en) 2014-09-04 2022-08-16 Intrance International Ab Pharmaceutical compositions comprising levodopa, a dopamine decarboxylase inhibitor and a COMT inhibitor and method of administration thereof
EP4356907A1 (fr) 2014-09-04 2024-04-24 LobSor Pharmaceuticals Aktiebolag Compositions pharmaceutiques comprenant de la lévodopa, un inhibiteur de la dopamine décarboxylase et un inhibiteur de la comt, et leur procédé d'administration
US10555922B2 (en) 2015-09-04 2020-02-11 Lobsor Pharmaceuticals Aktiebolag Method of treating a dopamine related disorder in a subject by administering levodopa, in combination with a dopamine decarboxylase inhibitor and a catechol-o-methyltransferase inhibitor
WO2019182506A1 (fr) 2018-03-23 2019-09-26 Lobsor Pharmaceuticals Aktiebolag Administration continue d'une composition pharmaceutique pour le traitement de troubles neurodégénératifs
US11547689B2 (en) 2018-03-23 2023-01-10 Intrance International Ab Continuous administration of pharmaceutical composition for treatment of neurodegenerative disorders

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