MXPA06008790A - Nueva forma cristalina iii de agomelatina, un proceso para su preparacion y composiciones farmaceuticas que la contienen. - Google Patents
Nueva forma cristalina iii de agomelatina, un proceso para su preparacion y composiciones farmaceuticas que la contienen.Info
- Publication number
- MXPA06008790A MXPA06008790A MXPA06008790A MXPA06008790A MXPA06008790A MX PA06008790 A MXPA06008790 A MX PA06008790A MX PA06008790 A MXPA06008790 A MX PA06008790A MX PA06008790 A MXPA06008790 A MX PA06008790A MX PA06008790 A MXPA06008790 A MX PA06008790A
- Authority
- MX
- Mexico
- Prior art keywords
- disorders
- agomelatine
- crystalline form
- pharmaceutical compositions
- form iii
- Prior art date
Links
- YJYPHIXNFHFHND-UHFFFAOYSA-N agomelatine Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(OC)=CC=C21 YJYPHIXNFHFHND-UHFFFAOYSA-N 0.000 title claims description 17
- 229960002629 agomelatine Drugs 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 238000010586 diagram Methods 0.000 claims abstract description 4
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000000634 powder X-ray diffraction Methods 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 230000007170 pathology Effects 0.000 claims description 7
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 6
- 206010022437 insomnia Diseases 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000019116 sleep disease Diseases 0.000 claims description 4
- 208000027559 Appetite disease Diseases 0.000 claims description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 3
- 229910052802 copper Inorganic materials 0.000 claims description 3
- 239000010949 copper Substances 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 210000002249 digestive system Anatomy 0.000 claims description 3
- 208000012672 seasonal affective disease Diseases 0.000 claims description 3
- 208000000044 Amnesia Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000032683 aging Effects 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 230000004087 circulation Effects 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 230000001193 melatoninergic effect Effects 0.000 claims description 2
- 230000006984 memory degeneration Effects 0.000 claims description 2
- 208000023060 memory loss Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 230000035882 stress Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 206010033664 Panic attack Diseases 0.000 claims 1
- 239000003433 contraceptive agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 208000019906 panic disease Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- -1 7-methoxy-1-naphthyl Chemical group 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 229960001021 lactose monohydrate Drugs 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- GABLTKRIYDNDIN-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1CCC(=O)C2=CC(OC)=CC=C21 GABLTKRIYDNDIN-UHFFFAOYSA-N 0.000 description 1
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Anesthesiology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente invencion describe la forma cristalina III del compuesto de formula (I): (ver formula I), caracterizada por su diagrama de difraccion de rayos X de polvo. Medicamentos.
Description
NUEVA FORMA CRISTALINA lll DE AGOMELATINA, lÍN PROCESO PARA SU PREPARACIÓN Y COMPOSICIONES
FARMACÉUTICAS QUE LA CONTIENEN
La presente invención se relaciona con una nueva forma cristalina lll de la agomelatina, o N-[2-(7-metoxi-1 -naftil)etiI]-acetamida, de fórmula (l):
con un proceso para su preparación y con composiciones farmacéuticas que lo contienen. La agomelatina o N-[2-(7-metoxi-1 -naftil)eti!]acetamida tiene propiedades farmacológicas valiosas. Efectivamente tiene la doble característica de ser, por un lado, un agonista de los receptores del sistema melatoninérgico y, por otro lado, un antagonista del receptor de 5-HT2C. Estas propiedades le confieren actividad en el sistema nervioso central y, más especialmente, en el tratamiento de la depresión severa, trasíornos afecíivos eslacionales, trastornos del sueño, patologías cardiovasculares, patologías del sistema digestivo, insomnio y fafiga que resultan del desfase de horario, trastornos del apetito y la obesidad.
La agomelatina, su preparación y su uso terapéutico han sido descritos en la Especificación de Patente Europea EP 0 447 285. En vista del valor farmacéutico de este compuesto, ha sido importante poder obtenerlo con excelente pureza, con una forma cristalina bien definida, perfectamente reproducible, que como resultado exhiba características valiosas en términos de formulación y suficientemenle esíable para permiíir su almacenamiento por periodos prolongados sin requerimientos particulares de íemperalura, luz, humedad o concentración de oxígeno. La Especificación de Patente EP 0 447 285 describe la preparación de agomelatina en ocho etapas, partiendo de 7-metoxi- 1 -tetralona. Sin embargo, ese documenío no especifica las condiciones para obtener agomelatina en una forma que exhiba estas características de una manera reproducible. La Solicitante ha desarrollado ahora un nuevo proceso de síntesis que permite que se obtenga agomelatina en una forma cristalina bien definida, perfectamente reproducible que exhibe especialmente caracterísficas valiosas para la formulación. Más específicamente, la presente invención se relaciona con la forma cristalina lll del compuesto de fórmula (I), caracterizada por el siguiente diagrama de difracción de rayos X de polvo, medido usando un difractómetro Siemens D5005 (anticátodo de cobre) y expresado en términos de distancia d inter-planar,
ángulo 2 tela de Bragg, intensidad e intensidad relativa (expresada como un porcentaje del rayo más intenso):
La invención se relaciona también con un proceso para la preparación de la forma cristalina lll del compuesto de fórmula (I), el proceso está caracterizado porque la agomelatina se calienta a 1 10° C hasta que la fusión es completa, y luego se enfría lentamente hasta cristalización. Una ventaja de obtener esta forma cristalina es que permite la preparación de formulaciones farmacéuticas que tienen una composición consistente y reproducible, la cual es
especialmente ventajosa cuando las formulaciones se van a usar para administración oral. Un estudio farmacológico de la forma lll así obtenida ha demostrado que tiene una actividad substancial respecto del sistema nervioso central y respecto de la microcirculación, permitiendo que se establezca que la forma cristalina lll de la agomelatina es útil en el tratamiento del estrés, trastornos del sueño, ansiedad, depresión severa, trastornos afectivos estacionales, patologías cardiovasculares, patologías del sistema digestivo, insomnio y faliga debidos al desfase de horario, esquizofrenia, aíaques de pánico, melancolía, trastornos del apetito, obesidad, insomnio, dolor, trastornos sicóticos, epilepsia, diabetes, enfermedad de Parkinson, demencia senil, diversos trastornos asociados con el envejecimiento normal o patológico, migraña, pérdida de memoria, enfermedad de Alzheimer y en trastornos de circulación cerebral. En otro campo de actividad, parece que la forma lll cristalina de la agomelatina se puede usar en el tratamiento de disfunciones sexuales, esto es, tiene propiedades inhibidoras de la ovulación e inmunomoduladoras y se presta para usarse en el tratamiento de cánceres. La forma cristalina ill de la agomelat?na preferentemente se usará en el tratamiento de la depresión severa, trastornos afectivos estacionales, trastornos del sueño, patologías cardiovasculares, insomnio y fatiga debidos al desfase de horario, trastornos del apetito y obesidad.
La invención se relaciona también con composiciones farmacéuticas que comprenden como ingrediente activo la forma cristalina lll de la agomelatina junto con uno o más excipientes apropiados, inertes, no tóxicos. Entre las composiciones farmacéuticas de acuerdo con la invención se pueden mencionar, más especialmeníe, aquellas que son adecuadas para administración oral, parenteral (intravenosa o subcutánea) o nasal, tablelas o grageas, granulos, tabletas sublinguales, cápsulas de gelatina, tableías con forma de rombo, suposiíorios, cremas, pomadas, geles dérmicos, preparaciones inyectables, suspensiones ingeribles y pastas que se pueden desintegrar. La dosificación útil se puede adaptar de acuerdo con la naturaleza y la severidad del trastorno, la ruta de administración y la edad y el peso del paciente. La dosificación varía desde 0.1 mg a 1 g por día en una o más administraciones. Los Ejemplos de abajo ilustran la invención pero no la limitan en modo alguno.
Eiemplo 1 : Forma cristalina lll de N-[2-(7-metoxi-1 -naftil)etil]- acetamida Se calentaron 100 g de N-[2-(7-metoxi-1 -naftil)etil]-acetamida a 1 10° C en una incubadora ventilada hasta que la fusión fue completa, y luego se enfriaron lentamenle hasta cristalización. La forma cristalina lll obtenida se caracterizó por el siguiente diagrama de difracción de rayos X de polvo, medido
usando un difractómetro Siemens D5005 (anticátodo de cobre) y expresado en términos de distancia d inter-planar, ángulo 2 teta de Bragg, intensidad e intensidad relativa (expresada como un porcentaje del rayo más intenso):
Eiemplo 2: Composición farmacéutica Formulación para la preparación de 1 ,000 tabletas, cada una contiene una dosis de 25 mg: Compuesto del Ejemplo 1 25 g Monohidrato de lacíosa 62 g Estearato de magnesio 1.3 g
Almidón de maíz 26 g Maltodextrinas 9 g Sílice coloidal anhidra 0.3 g Glicolato de almidón y sodio tipo A 4 g Ácido esteárico.... 2.6 g
Eiemplo 3: Composición farmacéutica Formulación para la preparación de 1 ,000 tabletas, cada una contiene una dosis de 25 mg: Compuesto del Ejemplo 1 25 g Monóhidrato de lactosa 62 g Estearato de magnesio 1.3 g Povidona 9 g Sílice coloidal anhidra 0.3 g Glicolato de celulosa y sodio 30 g Ácido esteárico 2.6 g
Claims (5)
1. Forma cristalina lli de agomelatina de fórmula (I): caracterizada por el siguiente el siguiente diagrama de difracción de rayos X de polvo, medido usando un difractómetro Siemens D5005 (anticátodo de cobre) y expresado en términos de distancia d inter-planar, ángulo 2 teta de Bragg, intensidad e intensidad relativa (expresada como un porcentaje del rayo más intenso):
2. Proceso para la preparación de la forma cristalina lll del compuesto de fórmula (I) según la reivindicación 1 , en donde la agomelatina se calienta a 1 10° C hasta que la fusión se completa, y luego se enfría lentamente hasta cristalización.
3. Composiciones farmacéuticas que comprenden como ingrediente activo la forma cristalina lll de agomelatina según la reivindicación 1 , en combinación con uno o más portadores farmacéuticamente aceptables, inertes y no tóxicos.
4. Composiciones farmacéuticas según la reivindicación 3, para usarse en la manufactura de un medicamento para el tratamiento de trastornos melatoninérgicos.
5. Composiciones farmacéuticas según la reivindicación 3, para usarse en la manufactura de un medicamento para el tratamiento de trastornos del sueño, estrés, ansiedad, trastornos afectivos estacionales o depresión severa, patologías cardiovasculares, patologías del sislema digestivo, insomnio y fatiga debidos al desfase de horario, esquizofrenia, ataques de pánico, melancolía, trastornos del apetito, obesidad, insomnio, trastornos sicóticos, epilepsia, diabetes, enfermedad de Parkinson, demencia senil, diversos trastornos asociados con el envejecimiento normal o patológico, migraña, pérdida de memoria, enfermedad de Alzheimer, trastornos de circulación cerebral y también en disfunciones sexuales, como inhibidores de la ovulación, inmunomoduladores y cánceres.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0508276A FR2889521B1 (fr) | 2005-08-03 | 2005-08-03 | Nouvelle forme cristalline iii de l'agomelatine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06008790A true MXPA06008790A (es) | 2008-02-04 |
Family
ID=36587257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06008790A MXPA06008790A (es) | 2005-08-03 | 2006-08-03 | Nueva forma cristalina iii de agomelatina, un proceso para su preparacion y composiciones farmaceuticas que la contienen. |
Country Status (35)
| Country | Link |
|---|---|
| EP (3) | EP1752445A1 (es) |
| JP (1) | JP4580370B2 (es) |
| CN (1) | CN100450995C (es) |
| AR (1) | AR057713A1 (es) |
| AU (1) | AU2006203336B2 (es) |
| BR (1) | BRPI0603074A (es) |
| CA (1) | CA2555117A1 (es) |
| CY (1) | CY1118637T1 (es) |
| DK (1) | DK2210872T3 (es) |
| EA (1) | EA011031B1 (es) |
| ES (1) | ES2614934T3 (es) |
| FR (1) | FR2889521B1 (es) |
| GE (1) | GEP20094576B (es) |
| GT (1) | GT200600347A (es) |
| HR (1) | HRP20170095T1 (es) |
| HU (1) | HUE030506T2 (es) |
| JO (1) | JO3360B1 (es) |
| LT (1) | LT2210872T (es) |
| MA (1) | MA28449B1 (es) |
| ME (1) | ME02689B (es) |
| MX (1) | MXPA06008790A (es) |
| MY (1) | MY142856A (es) |
| NO (1) | NO337010B1 (es) |
| NZ (1) | NZ548862A (es) |
| PE (1) | PE20070213A1 (es) |
| PL (1) | PL2210872T3 (es) |
| PT (1) | PT2210872T (es) |
| RS (1) | RS55499B1 (es) |
| SA (1) | SA06270253B1 (es) |
| SG (1) | SG130112A1 (es) |
| SI (1) | SI2210872T1 (es) |
| TW (1) | TWI389873B (es) |
| UA (1) | UA83719C2 (es) |
| WO (1) | WO2007015003A2 (es) |
| ZA (1) | ZA200606454B (es) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2934856B1 (fr) * | 2008-08-05 | 2010-08-13 | Servier Lab | Nouveau procede d'obtention de la forme cristalline v de l'agomelatine |
| CN101585779B (zh) * | 2009-03-10 | 2014-04-02 | 上海医药工业研究院 | 阿戈美拉汀的晶型vi及其制备方法和应用 |
| WO2011006387A1 (zh) * | 2009-07-11 | 2011-01-20 | 浙江华海药业股份有限公司 | 阿戈美拉汀的制备方法、阿戈美拉汀晶形及其制备方法 |
| CN102001959B (zh) * | 2009-09-01 | 2014-07-02 | 北京本草天源药物研究院 | 一种药物晶体及其制备方法和用途 |
| CN102050755B (zh) * | 2009-10-29 | 2014-11-05 | 重庆医药工业研究院有限责任公司 | 阿戈美拉汀的晶型及其制备方法 |
| CN101709036B (zh) * | 2009-12-17 | 2012-07-04 | 天津药物研究院 | 阿戈美拉汀中间体2-(7-甲氧基-1-萘基)乙胺的制备 |
| CN101781226B (zh) * | 2009-12-23 | 2012-03-28 | 天津泰普药品科技发展有限公司 | 阿戈美拉汀及其药物组合物 |
| CN101774937B (zh) * | 2010-02-05 | 2014-01-08 | 天津市汉康医药生物技术有限公司 | N-[2-(7-甲氧基-1-萘基)乙基]乙酰胺及其组合物 |
| CL2011001405A1 (es) | 2010-06-10 | 2012-03-30 | Gador S A Conicet | Procedimiento para la preparacion de n-[2-(7-metoxi-1-naftil)etil]acetamida, agometalina. |
| CZ303787B6 (cs) * | 2011-01-21 | 2013-05-02 | Zentiva, K.S. | Metastabilní krystalové formy agomelatinu a jejich farmaceutické kompozice |
| CN102690209A (zh) * | 2011-03-23 | 2012-09-26 | 上海医药工业研究院 | 阿戈美拉汀的混晶(形式-ⅷ)、其制备方法、应用和包含其的药物组合物 |
| CN102690210A (zh) * | 2011-03-23 | 2012-09-26 | 上海医药工业研究院 | 阿戈美拉汀的新晶型ⅶ、其制备方法、应用和包含其的药物组合物 |
| FR2978916B1 (fr) | 2011-08-10 | 2013-07-26 | Servier Lab | Composition pharmaceutique solide pour administration buccale d'agomelatine |
| EP2771312B1 (en) | 2011-11-30 | 2017-05-31 | ratiopharm GmbH | Agomelatine-urea complex and crystalline forms thereof |
| CZ2012108A3 (en) | 2012-02-15 | 2013-02-27 | Zentiva Ks | A method for the manufacture of a polymorphously stable pharmaceutical composition containing agomelatine |
| EP2934502A1 (en) | 2012-12-21 | 2015-10-28 | Laboratorios Lesvi S.L. | Process for prepararing n-(2-(7-methoxy-1-naphthalenyl)ethyl) acetamide and solid forms thereof |
| FR3001894A1 (fr) | 2013-02-08 | 2014-08-15 | Servier Lab | Composition pharmaceutique solide pour administration buccale d'agomelatine |
| ES2645223T3 (es) | 2013-06-06 | 2017-12-04 | Zentiva, K.S. | Formulaciones de agomelatina que comprenden agomelatina en forma de co-cristales |
| EP2810647A1 (en) | 2013-06-06 | 2014-12-10 | Zentiva, a.s. | Pharmaceutical formulations comprising agomelatine in the form of agomelatine co-crystal with an organic acid |
| CZ2013621A3 (cs) | 2013-08-13 | 2015-02-25 | Zentiva, K.S. | Termodynamicky stabilní tuhý roztok agomelatinu pro použití ve farmaceutické formulaci |
| WO2015124496A1 (en) | 2014-02-19 | 2015-08-27 | Synthon B.V. | Pharmaceutical composition comprising amorphous agomelatine |
| ES2959460T3 (es) | 2015-03-31 | 2024-02-26 | Fis Fabbrica Italiana Sintetici Spa | Forma sólida de agomelatina |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| FR2866336B1 (fr) * | 2004-02-13 | 2006-03-24 | Servier Lab | Nouveau procede de synthese du (7-methoxy-3,4-dihydro-1-naphtalenyl) acetonitrile et application a la synthese de l'agomelatine |
| FR2866335B1 (fr) * | 2004-02-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'agomelatine |
-
2005
- 2005-08-03 FR FR0508276A patent/FR2889521B1/fr active Active
-
2006
- 2006-07-19 PE PE2006000866A patent/PE20070213A1/es not_active Application Discontinuation
- 2006-07-24 MA MA29210A patent/MA28449B1/fr unknown
- 2006-07-24 JO JOP/2006/0245A patent/JO3360B1/ar active
- 2006-07-31 GT GT200600347A patent/GT200600347A/es unknown
- 2006-08-01 SG SG200605175-9A patent/SG130112A1/en unknown
- 2006-08-01 NZ NZ548862A patent/NZ548862A/en not_active IP Right Cessation
- 2006-08-01 SA SA06270253A patent/SA06270253B1/ar unknown
- 2006-08-02 SI SI200632141A patent/SI2210872T1/sl unknown
- 2006-08-02 HU HUE10003436A patent/HUE030506T2/en unknown
- 2006-08-02 UA UAA200608688A patent/UA83719C2/ru unknown
- 2006-08-02 DK DK10003436.2T patent/DK2210872T3/en active
- 2006-08-02 RS RS20161179A patent/RS55499B1/sr unknown
- 2006-08-02 MY MYPI20063735A patent/MY142856A/en unknown
- 2006-08-02 TW TW095128299A patent/TWI389873B/zh not_active IP Right Cessation
- 2006-08-02 EA EA200601274A patent/EA011031B1/ru not_active IP Right Cessation
- 2006-08-02 ES ES10003436.2T patent/ES2614934T3/es active Active
- 2006-08-02 PL PL10003436T patent/PL2210872T3/pl unknown
- 2006-08-02 EP EP06291253A patent/EP1752445A1/fr not_active Withdrawn
- 2006-08-02 PT PT100034362T patent/PT2210872T/pt unknown
- 2006-08-02 NO NO20063516A patent/NO337010B1/no not_active IP Right Cessation
- 2006-08-02 ME MEP-2017-33A patent/ME02689B/me unknown
- 2006-08-02 EP EP10003436.2A patent/EP2210872B1/fr active Active
- 2006-08-02 EP EP08017458A patent/EP2008993A1/fr not_active Withdrawn
- 2006-08-02 AR ARP060103364A patent/AR057713A1/es not_active Application Discontinuation
- 2006-08-02 WO PCT/FR2006/001868 patent/WO2007015003A2/fr active Application Filing
- 2006-08-02 GE GEAP20069558A patent/GEP20094576B/en unknown
- 2006-08-02 LT LTEP10003436.2T patent/LT2210872T/lt unknown
- 2006-08-03 MX MXPA06008790A patent/MXPA06008790A/es active IP Right Grant
- 2006-08-03 JP JP2006211620A patent/JP4580370B2/ja not_active Expired - Fee Related
- 2006-08-03 CN CNB2006101083967A patent/CN100450995C/zh not_active Expired - Fee Related
- 2006-08-03 CA CA002555117A patent/CA2555117A1/fr not_active Abandoned
- 2006-08-03 BR BRPI0603074-2A patent/BRPI0603074A/pt not_active Application Discontinuation
- 2006-08-03 ZA ZA200606454A patent/ZA200606454B/xx unknown
- 2006-08-03 AU AU2006203336A patent/AU2006203336B2/en not_active Ceased
-
2017
- 2017-01-20 HR HRP20170095TT patent/HRP20170095T1/hr unknown
- 2017-02-10 CY CY20171100190T patent/CY1118637T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MXPA06008790A (es) | Nueva forma cristalina iii de agomelatina, un proceso para su preparacion y composiciones farmaceuticas que la contienen. | |
| AU2006203340B2 (en) | New crystalline form IV of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| US8067639B2 (en) | Crystalline form VI of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| AU2006203342B2 (en) | New crystalline form V of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| US7358395B2 (en) | Crystalline form V of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| US7939566B2 (en) | Crystalline form III of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| US7910625B2 (en) | Crystalline form IV of agomelatine, a process for its preparation and pharmaceutical compositions containing it | |
| KR100904116B1 (ko) | 아고멜라틴의 ⅴ 결정형, 이의 제조 방법 및 이를 함유하는 약제 조성물 | |
| KR20070017019A (ko) | 아고멜라틴의 결정질 형태 ⅲ, 이의 제조 방법 및 이를함유하는 약제 조성물 | |
| KR20070017020A (ko) | 아고멜라틴의 결정질 형태 ⅳ, 이의 제조 방법 및 이를함유하는 약제 조성물 | |
| HK1098130B (en) | New crystalline form iii of agomelatine, a process for its preparation and pharmaceutical compositions containing it |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |