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WO2010027340A1 - Compositions pharmaceutiques d'entacapone, de levodopa et de carbidoba - Google Patents

Compositions pharmaceutiques d'entacapone, de levodopa et de carbidoba Download PDF

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Publication number
WO2010027340A1
WO2010027340A1 PCT/TR2009/000112 TR2009000112W WO2010027340A1 WO 2010027340 A1 WO2010027340 A1 WO 2010027340A1 TR 2009000112 W TR2009000112 W TR 2009000112W WO 2010027340 A1 WO2010027340 A1 WO 2010027340A1
Authority
WO
WIPO (PCT)
Prior art keywords
levodopa
granule
entakapon
carbidopa
entacapone
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/TR2009/000112
Other languages
English (en)
Inventor
Ebrahimi Sirin
Badem Gulhan
Agcayazi Mehmet
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.)
DR F FRIK ILAC SANAYI VE TICARET AS
Original Assignee
DR F FRIK 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 DR F FRIK ILAC SANAYI VE TICARET AS filed Critical DR F FRIK ILAC SANAYI VE TICARET AS
Publication of WO2010027340A1 publication Critical patent/WO2010027340A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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

Definitions

  • Present invention is related with stabile complexes consisting of entakapan, levodapa, and karbidopa or pharmaceutically acceptable salts, aqueous forms thereof or any kind of physicochemical polymorphs thereof, their processes of preparation for treatment of Parkinson disease and their processes of preparation.
  • Entakapon is a inhibitor of katekol - O - methyl transferase (COMT), in which molecular weight is 305,3. It is described like this in US Patent 4.446.194. Levodopa is used for the treatment of Parkinson disease - together with the treatment of karbidopa. Enteral and parenteral application types are discussed in US Patent No. 5.446.194. It is called as (E) - alpha - cyano - 3 - (3,4 - dihydroxy - 5 - nitrophenil) x N, N - diethyl - 2 propenamide chemically. Its empirical formula is Ci 4 Hi 5 N 3 O 5 and its structural formulation is given below:
  • Karbidopa is a peripheral decarboxylase inhibitor, having molecular weight
  • Levodopa is an aromatic amine, with molecular weight of 197,2, metabolized with dopamine. It was seen as a light in Parkinson disease treatment in 1960s, when it was first introduced for treatment. It is called as (-) - L - ⁇ - amino - ⁇ - (3,4 - dihydroxybenzene) propanoic acid chemically. Its empirical formula is CgHnNO 4 and its structural formula is given below:
  • Entakapon, nitekapon or pharmaceutically acceptable entakapon and nitekapon salts and oral composition at least 6 % more of total composition by weight compated with crosscarmellose in a tablet form are described in US Patent No. US 6.599.530.
  • US Patent No. 20060222703 describes pharmaceutical compositions achieved by simultaneous mixing of microcrystalline cellulose and starch together with entakapon, levodapa and karbidopa, that is each of the their actives. It is specified that said compositions are prepared by compaction granulation.
  • wet granulation method effects stability of the composition negatively and the dissolution values of entakapon, levodopa and karbidopa are decreased in wet granulation application.
  • entakapon levodopa and kabidopa or acceptable salt
  • the aqueous forms of these molecules or composition comprising each of their physicochemical polymorphs is achieved by substantial amount of entakopo is separated from levodopa and karbidopa mixture and consists of microcrystalline cellulose.
  • One of the subjects of the invention is to achieve a composition consisting of entakapon, levodopa and karbidopa or the acceptable salts, the aqueous form of these molecules or each of their physicochemical polymorphs in a pharmaceutically stable dose while karbidopa and entakapon are a compound, and levodopa is completely separated.
  • the invention finds a solution to the classification of the sectional factor described as "substantial portion” in the technologies involved in the patents which their numbers are given in the paragraphs above. It makes the processes easier not by separating one of the 3 factors in the formulation as a “substantial portion”, but by completely separating.
  • None of the entakapon, levodopa and karbidopa or their acceptable salts, aqueous forms or compositions consisting of each of their physicochemical polymorphs or no parts of the said compounds in the scope of the invention contains microcrystalline cellulose.
  • Pharmaceutical compounds my include one or more of materials having characteristics such as filler, binder, lubricant, glidant or disperser. There may be one or more auxiliary materials having the same characteristics.
  • the invention accepts entakapon and karbidopa or acceptable salts, aqueous forms of these molecules or their physicochemical polymorphs as a granulation phase while accepting the phase including levodopa or acceptable salts, aqueous forms of this molecule or its physicochemical polymorphs as a separate granulation phase.
  • Granulation method is determined as wet granulation and applied as such.
  • the phase including entakapon and karbidopa or acceptable salts, aqueous forms of these molecules or their physicochemical polymorphs and the phase including levodopa or acceptable salts, aqueous forms of this molecule or its physicochemical polymorphs mentioned above may have individually any one or more auxiliary materials with filler, binder, lubricant, glidant or disperser characteristics. There may be more than one auxiliary material with the same characteristics.
  • the separate phase specified in the scope of the invention, that is the phase including levodopa or acceptable salts, aqueous forms of this molecule or its physicochemical polymorphs may be in powder form or granules.
  • Compounds of the present invention are valid for single layer tablets, two layer tablets, mini tablets, tablets in capsules, granules in tablets, pellets, pellets in capsules, powder form, suspension and every other suitable pharmaceutical dose forms.
  • Owners of the invention proved that a single pharmaceutical form of a mixture of entakapon and karbidopa and levodopa as a substantially different phase can be formulated and produced to provide desired therapeutical effect without any stability problem.
  • microcrystalline celluse in the pharmaceutically stable composition containing entakapon, levodopa and karbidopa or acceptable salts, aqueous forms of these molecules or their physicochemical polymorphs and the phase including levodopa or acceptable salts, aqueous forms of this molecule or its physicochemical polymorphs.
  • entakapon levodopa and karbidopa or acceptable salts
  • phase including levodopa or acceptable salts, aqueous forms of this molecule or its physicochemical polymorphs.
  • composition is prepared in two phases.
  • the first phase is prepared as below: suitable filler material of entakapon and karbidopa is mixed with dispenser and binder until a homogeneous mixture is achieved, then formed into granules with the solution containing a suitable binder. Granules are dried and screened with a suitable filter.
  • the second phase is prepared as below: suitable filler material of levodopa is mixed with dispenser and binder in powder form until a homogeneous mixture is achieved, then formed into granules with the solution containing a suitable binder. Granules are dried and screened with a suitable filter.
  • granules are poured into a mixer and suitable amounts of dispenser, filler material and lubricant are added. Stirring is done until a homogeneous mixture is achieved.
  • granule mixture containing the three active materials, i.e. entakapon, levodopa and karbidopa which are turned into a pharmaceutical dosage form is prepared.
  • This mixture may be made as one layer tablets, two layer tablets, tablets, mini tablets, tablets in capsules, granules in capsules, pellets and pellets in capsules forms. Powder form and granule mixture is usually used in suspensions.
  • Suitable binders may be one or more from the group consisting of povidon and derivatives, starch and derivatives, stearic acid and derivatives, gums and derivatives, hydroxypropilmethyl cellulose etc.
  • Suitable filler materials may be one or more from the group consisting of lactose and derivatives, alcohol sugars (mannitol, xylitole, sorbitol, etc.) calcium phosphate, calcium sulphat, kaolin, granulated sugar etc.
  • Suitable lubricants may be one or more from the group consisting of magnesium stearate, zinc stearate, calcium stearate, stearic acid etc.
  • Suitable glidants may be one or more from the group consisting of talk, corn starch, etc.
  • Suitable dispensers may be one or more from the group consisting of starch, crosscarmellose sodium, crosspovidon, sodium starch glikolate and mixtures, etc.
  • Table 1 expresses the serial compounds of present invention.
  • composition related with finished product is prepared in two pieces.
  • entakapon, karbidopa, explotab, lactose, potato starch, and hydroxypropil cellulose are stirred in a mixer until a homogeneous mixture is achieved.
  • Wet granulation is applied to powder mixture by polyvinylpyrolidon. Then, it is dried and filtered.
  • levodopa, lactose and potato starch are weighted.
  • Wet granulation with polyvinylpyrolidon is applied. It is dried and filtered. Explotab and magnesium stearate is added. Then, the last dosage form is prepared after each of the two pieces combined by mixing.
  • the present invention is intended to use entakapon, levodopa and karbidopa or their pharmaceutically acceptable salts or hydrates for the production stage of a solid oral composition for Parkinson disease treatment and for the patients whom degradation is observed after the levodapo dosage has started to lost its effects.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (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)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Psychology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques stables d'entacapone, de levodopa et de carbidoba utilisées pour le traitement de la maladie de Parkinson. Lesdites compositions contiennent de l'entacapone, du levodopa et du carbidoba ou leurs sels pharmaceutiquement acceptables, des formes aqueuses de ces molécules, ainsi que toute forme de leurs polymorphes physicochimiques. L'invention concerne également la préparation de ces compositions.
PCT/TR2009/000112 2008-09-03 2009-09-03 Compositions pharmaceutiques d'entacapone, de levodopa et de carbidoba Ceased WO2010027340A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2008/06646A TR200806646A2 (tr) 2008-09-03 2008-09-03 Entakapon, levodopa ve karbidoba içeren farmasötik kombinasyonlar
TR2008/06646 2008-09-03

Publications (1)

Publication Number Publication Date
WO2010027340A1 true WO2010027340A1 (fr) 2010-03-11

Family

ID=41314610

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2009/000112 Ceased WO2010027340A1 (fr) 2008-09-03 2009-09-03 Compositions pharmaceutiques d'entacapone, de levodopa et de carbidoba

Country Status (2)

Country Link
TR (1) TR200806646A2 (fr)
WO (1) WO2010027340A1 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011107653A3 (fr) * 2010-03-04 2011-11-03 Orion Corporation Méthode de traitement de la maladie de parkinson
EP2656856A2 (fr) 2012-04-25 2013-10-30 Ali Raif Ilaç Sanayi ve Ticaret Anonim Sirketi Formulation de comprimé comprenant de la lévodopa, de la carbidopa, de l'entacapone assurant une libération prolongée
US11331293B1 (en) 2020-11-17 2022-05-17 Neuroderm, Ltd. Method for treatment of Parkinson's disease
US20230047847A1 (en) * 2013-03-13 2023-02-16 Neuroderm, Ltd. Method for treatment of parkinson's disease
US11844754B2 (en) 2020-11-17 2023-12-19 Neuroderm, Ltd. Methods for treatment of Parkinson's disease
US12161612B2 (en) 2023-04-14 2024-12-10 Neuroderm, Ltd. Methods and compositions for reducing symptoms of Parkinson's disease

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001001984A1 (fr) * 1999-06-30 2001-01-11 Orion Corporation Preparation pharmaceutique a base de levodopa/carbidopa/entacapone
WO2006051154A1 (fr) * 2004-11-10 2006-05-18 Orion Corporation Traitement du syndrome des jambes sans repos
US20060222703A1 (en) * 2005-04-01 2006-10-05 Iprbox Oy Pharmaceutical composition and preparation method thereof
WO2006131591A2 (fr) * 2005-06-08 2006-12-14 Orion Corporation Forme posologique destinee a etre administree par voie orale
WO2008053297A2 (fr) * 2006-10-30 2008-05-08 Wockhardt Research Centre Compositions pharmaceutiques comprenant l'entacapone, la lévodopa, et la carbidopa
WO2009098661A1 (fr) * 2008-02-06 2009-08-13 Wockhardt Research Centre Compositions pharmaceutiques d'entacapone, de lévodopa et de carbidopa à biodisponibilité améliorée

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001001984A1 (fr) * 1999-06-30 2001-01-11 Orion Corporation Preparation pharmaceutique a base de levodopa/carbidopa/entacapone
US20030017201A1 (en) * 1999-06-30 2003-01-23 Matti Virkki Pharmaceutical composition comprising entracapone, levodopa, and carbidopa
WO2006051154A1 (fr) * 2004-11-10 2006-05-18 Orion Corporation Traitement du syndrome des jambes sans repos
US20060222703A1 (en) * 2005-04-01 2006-10-05 Iprbox Oy Pharmaceutical composition and preparation method thereof
WO2006131591A2 (fr) * 2005-06-08 2006-12-14 Orion Corporation Forme posologique destinee a etre administree par voie orale
WO2008053297A2 (fr) * 2006-10-30 2008-05-08 Wockhardt Research Centre Compositions pharmaceutiques comprenant l'entacapone, la lévodopa, et la carbidopa
WO2009098661A1 (fr) * 2008-02-06 2009-08-13 Wockhardt Research Centre Compositions pharmaceutiques d'entacapone, de lévodopa et de carbidopa à biodisponibilité améliorée

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011107653A3 (fr) * 2010-03-04 2011-11-03 Orion Corporation Méthode de traitement de la maladie de parkinson
AU2011222856B2 (en) * 2010-03-04 2015-10-15 Orion Corporation Use of levodopa, carbidopa and entacapone for treating Parkinson's disease
EA026419B1 (ru) * 2010-03-04 2017-04-28 Орион Корпорейшн Применение леводопы, карбидопы и энтакапона для лечения болезни паркинсона
US10857120B2 (en) 2010-03-04 2020-12-08 Orion Corporation Use of levodopa, carbidopa and entacapone for treating Parkinson's disease
US11771675B2 (en) 2010-03-04 2023-10-03 Orion Corporation Use of levodopa, carbidopa and entacapone for treating Parkinson's disease
EP2656856A2 (fr) 2012-04-25 2013-10-30 Ali Raif Ilaç Sanayi ve Ticaret Anonim Sirketi Formulation de comprimé comprenant de la lévodopa, de la carbidopa, de l'entacapone assurant une libération prolongée
EP2656856A3 (fr) * 2012-04-25 2014-07-09 Ali Raif Ilaç Sanayi ve Ticaret Anonim Sirketi Formulation de comprimé comprenant de la lévodopa, de la carbidopa, de l'entacapone assurant une libération prolongée
US20230047847A1 (en) * 2013-03-13 2023-02-16 Neuroderm, Ltd. Method for treatment of parkinson's disease
US11331293B1 (en) 2020-11-17 2022-05-17 Neuroderm, Ltd. Method for treatment of Parkinson's disease
US11458115B2 (en) 2020-11-17 2022-10-04 Neuroderm, Ltd. Method for treatment of Parkinson's disease
US11844754B2 (en) 2020-11-17 2023-12-19 Neuroderm, Ltd. Methods for treatment of Parkinson's disease
US12161612B2 (en) 2023-04-14 2024-12-10 Neuroderm, Ltd. Methods and compositions for reducing symptoms of Parkinson's disease

Also Published As

Publication number Publication date
TR200806646A2 (tr) 2009-06-22

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