CA2352324A1 - Derivatives of (-)-venlafaxine and methods of preparing and using the same - Google Patents

Derivatives of (-)-venlafaxine and methods of preparing and using the same Download PDF

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CA2352324A1
CA2352324A1 CA002352324A CA2352324A CA2352324A1 CA 2352324 A1 CA2352324 A1 CA 2352324A1 CA 002352324 A CA002352324 A CA 002352324A CA 2352324 A CA2352324 A CA 2352324A CA 2352324 A1 CA2352324 A1 CA 2352324A1
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human
pharmaceutically acceptable
treating
venlafaxine
stereoisomer
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CA2352324C (en
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Thomas P. Jerussi
Chrisantha H. Senanayake
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Sunovion Pharmaceuticals Inc
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    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/64—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

Methods of preparing, and compositions comprising, derivatives of (-)-venlafaxine are disclosed. Also disclosed are methods of treating and preventing diseases and disorders including, but not limited to, affective disorders such as depression, bipolar and manic disorders, attention deficit disorder, attention deficit disorder with hyperactivity, Parkinson's disease, epilepsy, cerebral function disorders, obesity and weight gain, incontinence, dementia and related disorders.

Claims (60)

1. A pharmaceutical composition which comprises (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer and a pharmaceutically acceptable carrier or excipient.
2. The pharmaceutical composition of claim 1 wherein the (-)-venlafaxine derivative is selected from the group consisting of (-)-O-desmethylvenlafaxine, (-)-N-desmethylvenlafaxine, (-)-N,O-didesmethylvenlafaxine, and (-)-N,N-didesmethylvenlafaxine.
3. The pharmaceutical composition of claim 2 wherein the (-)-venlafaxine derivative is (-)-O-desmethylvenlafaxine or (-)-N,O-didesmethylvenlafaxine.
4. The pharmaceutical composition of claim 1 adapted for intravenous infusion, transdermal delivery, or oral delivery.
5. The pharmaceutical composition of claim 1 wherein the amount of (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, comprises greater than about 90% by weight of the total amount of racemic venlafaxine derivative.
6. The pharmaceutical composition of claim 1 wherein the (-)-venlafaxine derivative comprises a hydrochloride salt thereof.
7. The pharmaceutical composition of claim 1 wherein said pharmaceutically acceptable excipient comprises lactose, croscarmellose sodium, microcrystalline cellulose, pre-gelatinized starch, and magnesium stearate.
8. The pharmaceutical composition of claim 1 wherein said pharmaceutical composition is substantially free of all mono- or di-saccharides.
9. The pharmaceutical composition of claim 8 wherein said pharmaceutical composition is lactose-free.
10. The pharmaceutical composition of claim 1 wherein the (-)-venlafaxine derivative is (-)-O-desmethylvenlafaxine and the excipient comprises lactose.
11. The pharmaceutical composition of claim 10 wherein the excipient further comprises microcrystalline cellulose, pre-gelatinized starch, magnesium stearate, and croscarmellose sodium.
12. A pharmaceutical dosage form which comprises a therapeutically effective amount of (-)-venlafaxine derivative or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, and a pharmaceutically acceptable carrier or excipient.
13. The dosage form of claim 12 wherein said dosage form is a tablet or a capsule.
14. The dosage form of claim 12 adapted for intravenous infusion, transdermal delivery, or oral delivery.
15. The dosage form of claim 14 wherein the therapeutically effective amount is from about 10 mg to about 1000 mg.
16. The dosage form of claim 15 wherein the therapeutically effective amount is from about 50 mg to about 500 mg.
17. The dosage form of claim 16 wherein the therapeutically effective amount is from about 75 mg to about 350 mg.
18. A method of preparing (-)-N-desmethylvenlafaxine which comprises contacting a compound of Formula 5:

with a reductant for a time and at a temperature sufficient to form (t)-N-desmethylvenlafaxine, and isolating (-)-N-desmethylvenlafaxine therefrom.
19. The method of claim 18 wherein the reductant is BH3~Me2S.
20. A method of preparing (-)-N,N-didesmethylvenlafaxine which comprises contacting a compound of Formula 2:

with a reductant for a time and at a temperature sufficient to form (~)-N,N-didesmethylvenlafaxine, and isolating (-)-N,N-didesmethylvenlafaxine therefrom.
21. The method of claim 20 wherein the reductant is CoCl2/NaBH4.
22. A method of preparing (-)-O-desmethylvenlafaxine which comprises contacting (~)-venlafaxine with lithium diphenylphosphide for a time and at a temperature sufficient to form (~)-O-desmethylvenlafaxine, and isolating (-)-O-desmethylvenlafaxine therefrom.
23. Substantially pure (-)-O-desmethylvenlafaxine and pharmaceutically acceptable salts, solvates, and clathrates thereof.
24. Substantially pure (-)-N,O-didesmethylvenlafaxine and pharmaceutically acceptable salts, solvates, and clathrates thereof.
25. (-)-N-desmethylvenlafaxine and pharmaceutically acceptable salts, solvates, and clathrates thereof.
26. (-)-N,N-didesmethylvenlafaxine and pharmaceutically acceptable salts, solvates, and clathrates thereof.
27. A method of treating an affective disorder in a human which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
28. The method of treating an affective disorder in a human according to claim 27 in which said amount of (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, is sufficient to alleviate the affective disorder but insufficient to cause adverse effects associated with the administration of racemic venlafaxine.
29. The method of claim 27 wherein the affective disorder is selected from the group consisting of depression, attention deficit disorder, and attention deficit disorder with hyperactivity.
30. A method for treating obesity or weight gain in a human which comprises administering to a human in need of a reduction or maintenance in weight, a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate obesity or weight gain.
31. The method for treating obesity or weight gain in a human according to claim 30 wherein said amount is sufficient to alleviate obesity or weight gain but insufficient to cause the adverse effects associated with administration of racemic venlafaxine.
32. A method of treating disorders ameliorated by inhibition of neuronal monoamine reuptake in a human which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate said disorders.
33. The method of treating disorders ameliorated by inhibition of neuronal monoamine reuptake in a human according to claim 32 in which said amount is sufficient to alleviate said disorders but insufficient to cause adverse effects associated with administration of racemic venlafaxine.
34. The method of treating disorders ameliorated by inhibition of neuronal monoamine reuptake in a human according to claim 33 wherein said monoamine is dopamine.
35. The method of treating disorders ameliorated by inhibition of neuronal monoamine reuptake in a human according to claim 33 wherein said disorder is Parkinson's disease or epilepsy.
36. A method for treating cerebral function disorders in humans which comprises administering to a human or therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate cerebral function disorders.
37. The method for treating cerebral function disorders in a human according to claim 36 wherein said amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable thereof, substantially free of its (+) stereoisomer, is sufficient to alleviate cerebral function disorders but insufficient to cause adverse effects associated with administration of racemic venlafaxine.
38. The method for treating cerebral function disorders in a human according to claim 36 wherein said disorder is caused by a cerebrovascular disease.
39. The method for treating cerebral function disorders in a human according to claim 38 wherein said cerebrovascular disease is selected from the group consisting of cerebral infarction, cerebral bleeding, cerebral arteriosclerosis, cerebral venous thrombosis and head injuries.
40. The method for treating cerebral function disorders in a human according to claim 38 wherein said cerebral function disorder is selected from the group consisting of senile dementia, Alzheimer's type dementia, memory loss and amnesia/amnestic syndrome.
41. A method for treating pain in humans which comprises administering to a human a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, said amount being sufficient to alleviate pain.
42. The method for treating pain in a human according to claim 41 wherein said amount of (-)-venlafaxine derivative, or a pharmaceutically acceptable thereof, substantially free of its (+) stereoisomer, is sufficient to alleviate pain but insufficient to cause adverse effects associated with administration of racemic venlafaxine.
43. The method for treating pain in a human according to claim 41 wherein the pain is chronic pain.
44. A method of treating an obsessive-compulsive disorder in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
45. A method of treating substance abuse in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
46. A method of treating or preventing pre-menstrual syndrome in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
47. A method of treating anxiety in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
48. A method of treating an eating disorder in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
49. A method of treating or preventing migraine, or migraine headaches, in a human, which comprises administering to a human in need of such therapy a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer.
50. A method for treating or preventing incontinence in a human which comprises administering to a human in need of such therapy, a therapeutically effective amount of a (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof substantially free of its (+) stereoisomer.
51. The method of claim 50 wherein said incontinence is selected from the group consisting fecal incontinence, overflow incontinence, passive incontinence, reflex incontinence, stress urinary incontinence, urge incontinence, urinary exertional incontinence, and incontinence of urine.
52. The method of claim 27 wherein the (-)-venlafaxine derivative is selected from the group consisting of (-)-O-desmethylvenlafaxine, (-)-N-desmethylvenlafaxine, (-)-N,O-didesmethylvenlafaxine, and (-)-N,N-didesmethylvenlafaxine.
53. The method of claim 52 wherein the (-)-venlafaxine derivative is (-)-O-desmethylvenlafaxine or (-)-N,O-didesmethylvenlafaxine.
54. The method of claim 27 wherein (-)-venlafaxine derivative is administered by intravenous infusion, transdermal delivery, or orally as a tablet or a capsule.
55. The method of claim 27 wherein the amount administered is from about 10 mg to about 1000 mg per day.
56. The method of claim 55 wherein the amount administered is from about 50 mg to about 500 mg per day.
57. The method of claim 56 wherein the amount administered is from about 75 mg to about 350 mg per day.
58. The method of claim 27 wherein the amount of (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, is greater than approximately 90%
by weight of the total amount of racemic venlafaxine derivative.
59. The method of claim 27 wherein the (-)-venlafaxine derivative, or a pharmaceutically acceptable salt thereof, substantially free of its (+) stereoisomer, is administered together with a pharmaceutically acceptable carrier.
60. The method of claim 27 wherein the (-)-venlafaxine derivative is administered as a hydrochloride salt.
CA2352324A 1998-12-01 1999-12-01 Derivatives of (-)-venlafaxine and methods of preparing and using the same Expired - Fee Related CA2352324C (en)

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US11048898P 1998-12-01 1998-12-01
US60/110,488 1998-12-01
US09/450,690 US6342533B1 (en) 1998-12-01 1999-11-30 Derivatives of (−)-venlafaxine and methods of preparing and using the same
US09/450,690 1999-11-30
PCT/US1999/028303 WO2000032556A1 (en) 1998-12-01 1999-12-01 Derivatives of (-)-venlafaxine and methods of preparing and using the same

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EP (2) EP1953136A1 (en)
JP (3) JP2003524613A (en)
AU (1) AU774408B2 (en)
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7208010B2 (en) 2000-10-16 2007-04-24 Conor Medsystems, Inc. Expandable medical device for delivery of beneficial agent
US6241762B1 (en) * 1998-03-30 2001-06-05 Conor Medsystems, Inc. Expandable medical device with ductile hinges
US6342533B1 (en) 1998-12-01 2002-01-29 Sepracor, Inc. Derivatives of (−)-venlafaxine and methods of preparing and using the same
US20020022662A1 (en) * 1999-06-15 2002-02-21 American Home Products Corporation Enantiomers of O-desmethyl venlafaxine
WO2000076955A1 (en) * 1999-06-15 2000-12-21 American Home Products Corporation Enantiomers of o-desmethyl venlafaxine
US20020035158A1 (en) * 1999-06-15 2002-03-21 American Home Products Corporation Enantiomers of N-desmethyl venlafaxine
WO2000076956A2 (en) * 1999-06-15 2000-12-21 American Home Products Corporation Enantiomers of n-desmethyl venlafaxine
US6348494B1 (en) 2000-11-21 2002-02-19 American Home Products Corporation Ethers of o-desmethyl venlafaxine
US7291646B2 (en) 1999-11-24 2007-11-06 Wyeth Ethers of O-desmethyl venlafaxine
CN1407890A (en) * 2000-03-07 2003-04-02 伊莱利利公司 Treatment of psoriasis
DE10042412B4 (en) * 2000-08-30 2005-12-22 Lts Lohmann Therapie-Systeme Ag Transceiver for bus subscriber of bus system of building system engineering, has two wires, where microcontroller is connected with receiver unit over connection on one hand, which is connected to two wires of bus system
WO2002032347A2 (en) 2000-10-16 2002-04-25 Conor Medsystems, Inc. Expandable medical device for delivery of beneficial agent
US20030232890A1 (en) 2000-11-01 2003-12-18 Sention, Inc. Methods for treating an impairment in memory consolidation
US7619005B2 (en) 2000-11-01 2009-11-17 Cognition Pharmaceuticals Llc Methods for treating cognitive impairment in humans with Multiple Sclerosis
US6828351B2 (en) 2000-11-01 2004-12-07 Sention, Inc. Methods and compositions for regulating memory consolidation
EP2319826A1 (en) * 2001-02-12 2011-05-11 Wyeth LLC Succinate salt of O-desmethyl-venlafaxin
US7842083B2 (en) * 2001-08-20 2010-11-30 Innovational Holdings, Llc. Expandable medical device with improved spatial distribution
UA80543C2 (en) * 2001-12-04 2007-10-10 Wyeth Corp Method for the preparation of o-desmethylvenlafaxine
US7005138B2 (en) * 2001-12-21 2006-02-28 Duramed Pharmaceuticals, Inc. Method of systematically delivering SSRIs
EP1474123A1 (en) * 2002-01-03 2004-11-10 LEK Pharmaceuticals D.D. Controlled release pharmaceutical formulation containing venlafaxine
AU2003226751A1 (en) 2002-03-28 2003-10-13 Synthon B.V. Low water-soluble venlafaxine salts
US6717015B2 (en) 2002-03-28 2004-04-06 Synthon Bv Venlafaxine besylate
EP1519720A4 (en) * 2002-06-10 2010-02-10 Wyeth Corp Novel formate salt of o-desmethyl-venlafaxine
WO2004006903A1 (en) * 2002-07-12 2004-01-22 Arakis Ltd. The treatment of emesis
CN1232501C (en) * 2002-11-29 2005-12-21 重庆凯林制药有限公司 Preparing technology for cyclohexanol derivatives used to prepare the intermediate of Venlafaxine
WO2004056335A2 (en) * 2002-12-23 2004-07-08 Osmotica Costa Rica Sociedad Anonima Delivery device containing venlafaxine and memantine and use method thereof
US20070077301A1 (en) * 2002-12-23 2007-04-05 Meyer Glenn A Venlafaxine osmotic device formulation
US7470435B2 (en) * 2003-11-17 2008-12-30 Andrx Pharmaceuticals, Llc Extended release venlafaxine formulation
ES2515092T3 (en) * 2003-12-11 2014-10-29 Sunovion Pharmaceuticals Inc. Combination of a sedative and a neurotransmitter modulator and methods of improving sleep quality and treating depression
CA2554559A1 (en) * 2004-02-06 2005-08-25 Wyeth Multiparticulate o-desmethylvenlafaxine salts and uses thereof
US7417009B2 (en) * 2004-03-26 2008-08-26 Nalco Company Paraffin inhibitors
US7776358B2 (en) 2004-07-22 2010-08-17 Synthon Ip Inc. Extended release venlafaxine besylate tablets
US20060228413A1 (en) * 2005-02-28 2006-10-12 Penwest Pharmaceuticals Co. Controlled release venlafaxine formulations
MX2008000248A (en) * 2005-07-06 2008-03-19 Sepracor Inc Combinations of eszopiclone and an antidepressant.
MX2008000249A (en) * 2005-07-06 2008-03-18 Sepracor Inc Combinations of eszopiclone and o-desmethylvenlafaxine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders.
GT200600397A (en) * 2005-09-07 2007-08-28 TOPIC FORMULAS CONTAINING O-DESMETIL VENLAFAXINA (ODV) OR ITS SALTS
WO2007047972A2 (en) * 2005-10-19 2007-04-26 Teva Pharmaceutical Industries Ltd. Process for the preparation of highly pure 1-[2-dimethylamino-(4-methoxyphenyl) ethyl]cyclohexanol hydrochloride
CA2632561C (en) * 2005-12-19 2015-01-27 The University Of Liverpool Substituted propofol derivatives as analgesics
WO2007071404A1 (en) 2005-12-20 2007-06-28 Synthon B.V. Process for making desvenlafaxine
EP1980271A4 (en) * 2006-01-27 2012-04-25 Asahi Kasei Pharma Corp Medicine for transnasal administration
TW200806282A (en) * 2006-05-05 2008-02-01 Wyeth Corp Solid dosage formulations
US20080081067A1 (en) * 2006-10-03 2008-04-03 Gupta Manishkumar Sustained release pharmaceutical compositions of venlafaxine and process for preparation thereof
CA2674034A1 (en) * 2007-01-09 2008-07-17 Pharmathen S.A. Improved process for the preparation of phenethylamine derivatives
CN101663263A (en) * 2007-02-21 2010-03-03 塞普拉柯公司 Solid forms comprising (-) o-desmethylvenlafaxine and uses thereof
CN101938998A (en) * 2007-10-16 2011-01-05 阿尔法制药有限公司 Controlled-release pharmaceutical formulation
AU2008315740A1 (en) 2007-10-26 2009-04-30 Generics [Uk] Limited Process for preparing O-desmethylvenlafaxine
EP2074993A1 (en) 2007-12-19 2009-07-01 Biovail Laboratories International S.r.l. Venlafaxine-containing film-coated modified-release tablets
WO2009084037A2 (en) * 2007-12-20 2009-07-09 Calyx Chemicals And Pharmaceuticals Ltd. Novel process for preparation of o-desmethylvenlafaxine
WO2009144517A1 (en) * 2008-04-14 2009-12-03 Egis Gyógyszergyár Nyilvánosan Müködö Process for the preparation of cyclohexanol derivatives
WO2010090991A1 (en) * 2009-02-04 2010-08-12 Supernus Pharmaceuticals, Inc. Formulations of desvenlafaxine
CZ303249B6 (en) 2010-04-06 2012-06-20 Zentiva, K.S. Process for preparing 4-(2-(substituted)-1-(1-hydroxycyclohexyl)ethyl)phenols by O-demethylation of their methyl ethers using odor free aromatic thiols
US8933123B2 (en) 2010-10-08 2015-01-13 Cadila Healthcare Limited Polymorphic forms of O-desmethyl-venlafaxine succinate
CN104529797A (en) * 2014-12-05 2015-04-22 南昌市博泽康医药科技有限公司 Preparation of venlafaxine hydrochloride chiral crystal form
CN106692118A (en) * 2016-11-18 2017-05-24 广州军区广州总医院 Application of venlafaxine to preparation of medicine for preventing or treating cognition function impairment after mTBI (mild traumatic brain injury)

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3536809A (en) 1969-02-17 1970-10-27 Alza Corp Medication method
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4008719A (en) 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
US4535186A (en) * 1983-04-19 1985-08-13 American Home Products Corporation 2-Phenyl-2-(1-hydroxycycloalkyl or 1-hydroxycycloalk-2-enyl)ethylamine derivatives
IE56324B1 (en) 1982-12-13 1991-06-19 American Home Prod Phenethylamine derivatives and intermediates therefor
US4761501A (en) 1983-10-26 1988-08-02 American Home Products Corporation Substituted phenylacetamides
DE3583307D1 (en) * 1984-05-10 1991-08-01 Ciba Geigy Ag Benzo-(pyrano und thiopyrano)-pyridine.
IE58110B1 (en) 1984-10-30 1993-07-14 Elan Corp Plc Controlled release powder and process for its preparation
US5073543A (en) 1988-07-21 1991-12-17 G. D. Searle & Co. Controlled release formulations of trophic factors in ganglioside-lipsome vehicle
GB8902209D0 (en) 1989-02-01 1989-03-22 Wyeth John And Brother Limited Preparation of cyclohexanol derivatives and novel thioamide intermediates
IT1229203B (en) 1989-03-22 1991-07-25 Bioresearch Spa USE OF 5 METHYLTHETRAHYDROPHOLIC ACID, 5 FORMYLTHETRAHYDROPHOLIC ACID AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS FOR THE PREPARATION OF PHARMACEUTICAL COMPOSITIONS IN THE FORM OF CONTROLLED RELEASE ACTIVE IN THE THERAPY OF MENTAL AND ORGANIC DISORDERS.
US5120548A (en) 1989-11-07 1992-06-09 Merck & Co., Inc. Swelling modulated polymeric drug delivery device
US5733566A (en) 1990-05-15 1998-03-31 Alkermes Controlled Therapeutics Inc. Ii Controlled release of antiparasitic agents in animals
US5281624A (en) 1991-09-27 1994-01-25 Eli Lilly And Company N-alkyl-3-phenyl-3-(2-substituted phenoxy) propylamines and pharmaceutical use thereof
US5580578A (en) 1992-01-27 1996-12-03 Euro-Celtique, S.A. Controlled release formulations coated with aqueous dispersions of acrylic polymers
WO1994000047A1 (en) 1992-06-23 1994-01-06 Sepracor Inc. Methods and compositions for treating depression and other disorders using optically pure (+) sibutramine
JPH08500093A (en) 1992-06-23 1996-01-09 セプラコア インコーポレーテッド Methods and compositions for treating depression and other disorders using optically pure (-) sibutramine
US5591767A (en) 1993-01-25 1997-01-07 Pharmetrix Corporation Liquid reservoir transdermal patch for the administration of ketorolac
DE69434872T2 (en) 1993-06-28 2007-04-05 Wyeth New treatments using phenethyl derivatives
TW344661B (en) 1993-11-24 1998-11-11 Lilly Co Eli Pharmaceutical composition for treatment of incontinence
EP0737189B1 (en) * 1993-12-28 1999-07-28 PHARMACIA & UPJOHN COMPANY Heterocyclic compounds for the treatment of cns and cardiovascular disorders
EP1245228A3 (en) * 1994-02-14 2002-10-09 Wyeth Medicament for the inducement of cognition enhancement
IT1270594B (en) 1994-07-07 1997-05-07 Recordati Chem Pharm CONTROLLED RELEASE PHARMACEUTICAL COMPOSITION OF LIQUID SUSPENSION MOGUISTEIN
US5506270A (en) * 1995-01-30 1996-04-09 American Home Products Corporation Venlafaxine in the treatment of hypothalamic amenorrhea in non-depressed women
US5554383A (en) 1995-04-06 1996-09-10 Trustees Of Tufts College Veterinary method for clinically modifying the behavior of dogs exhibiting canine affective aggression
US5541199A (en) * 1995-06-02 1996-07-30 American Home Products Corporation Chroman-2-ylmethylamino derivatives
JPH08333340A (en) * 1995-06-06 1996-12-17 Fujirebio Inc Production of aminoethylpiperidine derivative
US6274171B1 (en) * 1996-03-25 2001-08-14 American Home Products Corporation Extended release formulation of venlafaxine hydrochloride
ATE227278T1 (en) * 1996-04-19 2002-11-15 Akzo Nobel Nv SUBSTITUTED BENZYLAMINE DERIVATIVES AND THEIR USE FOR TREATING DEPRESSION
AU3075197A (en) 1996-05-21 1997-12-09 United States Of America, Represented By The Secretary, Department Of Health And Human Services, The Novel methods of o-demethylation and n-deprotection
WO1999016417A1 (en) 1997-10-01 1999-04-08 Flemington Pharmaceutical Corporation Buccal, polar and non-polar spray or capsule
US6342533B1 (en) * 1998-12-01 2002-01-29 Sepracor, Inc. Derivatives of (−)-venlafaxine and methods of preparing and using the same
US6197828B1 (en) 1998-12-01 2001-03-06 Sepracor, Inc. Derivatives of (+)-venlafaxine and methods of preparing and using the same
NZ514612A (en) 1999-04-06 2004-01-30 Sepracor Inc Derivatives of venlafaxine and methods of preparing and using the same
ES2250141T5 (en) 1999-05-27 2009-11-05 Acusphere, Inc. POROUS MATRICES OF DRUGS AND METHODS TO MANUFACTURE THEM.
WO2000076955A1 (en) 1999-06-15 2000-12-21 American Home Products Corporation Enantiomers of o-desmethyl venlafaxine
US20020022662A1 (en) * 1999-06-15 2002-02-21 American Home Products Corporation Enantiomers of O-desmethyl venlafaxine
WO2000078955A1 (en) 1999-06-18 2000-12-28 Biotherapies, Inc. Epithelial cell growth inhibitors
EP2319826A1 (en) * 2001-02-12 2011-05-11 Wyeth LLC Succinate salt of O-desmethyl-venlafaxin
UA80543C2 (en) * 2001-12-04 2007-10-10 Wyeth Corp Method for the preparation of o-desmethylvenlafaxine
EP1519720A4 (en) * 2002-06-10 2010-02-10 Wyeth Corp Novel formate salt of o-desmethyl-venlafaxine
TWI306092B (en) * 2003-03-11 2009-02-11 Wyeth Corp Process for preparation of phenethylamine derivatives
CA2554559A1 (en) * 2004-02-06 2005-08-25 Wyeth Multiparticulate o-desmethylvenlafaxine salts and uses thereof

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