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WO2012028834A1 - Use of bupropion in treating sexual dysfunction - Google Patents

Use of bupropion in treating sexual dysfunction Download PDF

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Publication number
WO2012028834A1
WO2012028834A1 PCT/GB2010/001649 GB2010001649W WO2012028834A1 WO 2012028834 A1 WO2012028834 A1 WO 2012028834A1 GB 2010001649 W GB2010001649 W GB 2010001649W WO 2012028834 A1 WO2012028834 A1 WO 2012028834A1
Authority
WO
WIPO (PCT)
Prior art keywords
patient
bupropion
sexual desire
acid addition
desire
Prior art date
Application number
PCT/GB2010/001649
Other languages
French (fr)
Inventor
Marcel Petrus Maria Bartels
David Llewellyn
Original Assignee
Marcel Petrus Maria Bartels
David Llewellyn
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 Marcel Petrus Maria Bartels, David Llewellyn filed Critical Marcel Petrus Maria Bartels
Priority to PCT/GB2010/001649 priority Critical patent/WO2012028834A1/en
Publication of WO2012028834A1 publication Critical patent/WO2012028834A1/en

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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
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives

Definitions

  • the invention relates to the use of BUPROPION also known as
  • the compound ( ⁇ )-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one has been used as an antidepressant and lately as an anti smoking medication.
  • certain side effects came to light which included a heightening of sexual desire and ability to reach orgasm particularly in females.
  • Bupropion acts as a dopamine reuptake inhibitor ( DRI ) norepinephrine reuptake inhibitor ( RI ) and as a nicotinic acetylcholine receptor agonist. It is therefore well suited as an antidepressant for which it has been previously prescribed and as the anti smoking aid that it is presently prescribed for.
  • the instant invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders of sexual desire.
  • the invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of HYPOACTIVE SEXUAL DESIRE DISORDER, loss of sexual desire, lack of sexual desire, deaeased sexual desire, inhibited sexual desire, loss of libido, libido disturbance and frigidity.
  • BUPROPION optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of
  • the invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted add addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of HYPOACTIVE SEXUAL DESIRE DISORDER and loss of sexual desire,
  • BUPROPION optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of female sexual dysfunction is preferred.
  • BUPROPION can be optionally used in the form of pharmaceutically acceptable acid addition salts.
  • Suitable acid addition salts include, for example, those of the acids selected from, succinic acid, hydrobromic acid.acetic acid, fumaric acid, maleic acid, methanesuphonic acid, lactic acid, phosphoric acid, hydrochloric acid, sulphuric acid, tartaric acid, and citric acid. Mixtures of the above mentioned acid addition salts can also be used. From the aforementoned acid addition salts the hydrochloride and the hydrobromide, particulairly the hydrochloride, are preferred.
  • BUPROPION optionally used in the form of pharmaceutically acceptable acid addition salts may be incorporated into the conventional pharmaceutical preparation in solid liquid or spray form.
  • the composition may, for example, be presented in a form suitable for oral, rectal, parental administration, or for nasal inhalation.
  • Preferred forms include for example, capsules, tablets, coated tablets, ampoules, suppositories and nasal spray.
  • the active ingredient may be incorporated in excipients and carriers conventionally used in pharmaceutical compositions such as, for example, talc, arabic gum, lactose, gelatine, magnesium stearate, corn starch, aqueous or non-aqueous vehicles, polyvinyl pyrolidone, semi-synthetic glycerides of fatty acids, benzalconium chloride, sodium phosphate, EDTA, polysorbate 80.
  • the compositions- are advantageously formulated in doseage units each doseage unit being adapted to supply a single dose of the active ingredient.
  • the dosis range applicable per day is between 0.1 mg to 1000mg, preferably between 1.0mg and 900mg, more preferably between 10mg and 800mg.
  • Each doseage unit may conveniently contain from 0.25mg to 300mg, preferably 1 mg to 200mg.
  • Suitable tablets may be obtained, for example, by mixing the active substances with known excipients, for example inert diluents such as calcium carbonate, calcium phosphate, or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatine, lubricants such as magnesium stearate or talc and / oragents for delaying release such as carboxymethyl cellulose, cellulose acetate phthalate or polyvinyl acetate.
  • excipients for example inert diluents such as calcium carbonate, calcium phosphate, or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatine, lubricants such as magnesium stearate or talc and / oragents for delaying release such as carboxymethyl cellulose, cellulose acetate phthalate or polyvinyl acetate.
  • the tablets may also comprise several layers.
  • Coated tablets may be prepared accordingly by coating cores produced analogously to the tablets with substances normally used for tablet coatings, for example collidone or shellack, gum arabic, talc , titanium dioxide or sugar.
  • substances normally used for tablet coatings for example collidone or shellack, gum arabic, talc , titanium dioxide or sugar.
  • the core may also consist of a number of layers to achieve the delayed release, possibly using the excipients mentioned above for the tablets.
  • Syrups or elixirs containing the active substances or combinations thereof according to the invention may additionally contain a sweetener such as saccharin, cyclamate, glycerol or sugar and a flavour enhancer eg
  • flavouring such as vanilla or orange extract.
  • suspension adjuvants or thickeners such as sodium carboxymethyl cellulose, wetting agents such as, for example, condensation products of fatty alcohols
  • preservatives such as p-hydroxybenzoates or stabilisers such as alkali metal saltsof ethylenediamine tetra acetic acid, and transferred to into injection vials or ampoules.
  • Capsules containing one or more active substances may for example be prepared by mixing the active substances with inert carriers such as lactose or sorbitol and packing them into gelatine capsules.
  • Suitable suppositories may be made for example by mixing with carriers provided this purpose, such as neutral fats or polyethyleneglycol or the derivatives thereof.
  • the finely ground active substance, lactose and some of the corn starch are mixed together.
  • the mixture is screened, then moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet-granulated and dried.
  • the granules, the remaining corn starch and the magnesium stearate are screened and mixed together.
  • the mixture is compressed to produce tablets of a suitable shape and size.
  • the finely ground active substance, some of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is screened and workedwith the remaining corn starch and water to form a granulate which is dried and screened.
  • the sodium carboxymethyl starch and the magnesium stearate are added and mixed inand the mixture is compressed to form tablets of a suitable size.
  • the active substance, corn starch, lactose, and polyvinylpyrrolidone are thoroughly mixed and moistened with water.
  • the moist mass is pushed through a screenwith a 1mm mesh size, dried at 45 degrees C and the granules are then passed through the same screen.
  • convextablet cores with a diameter of 6mm are compressed in a tablet-making machine.
  • the tablet cores thus produced are coated in known manner with a covering consisting of sugar and talc.
  • the finished coated tablets are polished with wax.
  • the substance and corn starch are mixed and moistened with water.
  • the moist mass is screened and dried.
  • the dry granules are screened and mixed withmagnesium stearate.
  • the finished mixture is packed into size 1 hard gelatine capsules.
  • the active substance is dissolved in water at its own pH or optionally at pH 5.5 -6.5 and sodium chloride is added to make it isotonic.
  • the solution obtained is filtered free from pyrogens and the filtrate is transferred under
  • the hard fat is melted. At 40 degrees C the ground active substance is homogenously dispersed. It is cooled to 38 degrees C and poured into slightly chilled suppository moulds.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (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

The invention relates to the use of BUPROPION (±)-2-(tert-butylamino)-1 -(3- chlorophenyl)propan-1-one and its ( ++ ) and ( -- ) isomeric forms or a pharmaceutically acceptable acid addition salt thereof, for the treatment of disorders of sexual desire, especially, though not limited to, patients of the female gender. The invention relates to the physical improvement of orgasm in patients who until now may have had difficulty in achieving sexual satisfaction.

Description

USE OF BUPROPION IN TREATING SEXUAL DYSFUNCTION
FIELD OF THE INVENTION
The invention relates to the use of BUPROPION also known as
(±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one for the preparation of a medicament for the treatment of physical disorders of sexual desire.
BACKGROUND OF THE INVENTION
The compound (±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one has been used as an antidepressant and lately as an anti smoking medication. During testing of the compound certain side effects came to light which included a heightening of sexual desire and ability to reach orgasm particularly in females.
Bupropion acts as a dopamine reuptake inhibitor ( DRI ) norepinephrine reuptake inhibitor ( RI ) and as a nicotinic acetylcholine receptor agonist. It is therefore well suited as an antidepressant for which it has been previously prescribed and as the anti smoking aid that it is presently prescribed for.
DETAILED DESCRIPTION OF THE INVENTION
In studies of male and female patients suffering from sexual dysfunction it has been found that BUPROPION optionally in the form of the pharmalogically accepted acid addition salts thereof displays sexual enhancing properties. Accordingly , the instant invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders of sexual desire.
In a preferred embodiment the invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of HYPOACTIVE SEXUAL DESIRE DISORDER, loss of sexual desire, lack of sexual desire, deaeased sexual desire, inhibited sexual desire, loss of libido, libido disturbance and frigidity. Particularly preferred according to the invention is the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of
HYPOACTIVE SEXUAL DESIRE DISORDER, loss of sexual desire, lack of sexual desire, decreased sexual desire, and inhibited sexual desire,
In a particularily preferred embodiment the invention relates to the use of BUPROPION, optionally in form of the pharmalogically accepted add addition salts thereof for the preparation of a medicament for the treatment of disorders selected from the group consisting of HYPOACTIVE SEXUAL DESIRE DISORDER and loss of sexual desire,
The observed effects of BUPROPION can be achieved in both men and women.
However, according to a further aspect of the invention the use of BUPROPION, optionally in form of the pharmalogically accepted acid addition salts thereof for the preparation of a medicament for the treatment of female sexual dysfunction is preferred.
The beneficial effects of BUPROPION can be observed regardless of whether the disturbance existed lifelong or was acquired, and was independent of etiologic origin ( organic - both, physically and drug induced-, a combination of organic - both, physically and drug induced-, or unknown).
BUPROPION can be optionally used in the form of pharmaceutically acceptable acid addition salts. Suitable acid addition salts include, for example, those of the acids selected from, succinic acid, hydrobromic acid.acetic acid, fumaric acid, maleic acid, methanesuphonic acid, lactic acid, phosphoric acid, hydrochloric acid, sulphuric acid, tartaric acid, and citric acid. Mixtures of the above mentioned acid addition salts can also be used. From the aforementoned acid addition salts the hydrochloride and the hydrobromide, particulairly the hydrochloride, are preferred.
BUPROPION, optionally used in the form of pharmaceutically acceptable acid addition salts may be incorporated into the conventional pharmaceutical preparation in solid liquid or spray form. The composition may, for example, be presented in a form suitable for oral, rectal, parental administration, or for nasal inhalation. Preferred forms include for example, capsules, tablets, coated tablets, ampoules, suppositories and nasal spray. The active ingredient may be incorporated in excipients and carriers conventionally used in pharmaceutical compositions such as, for example, talc, arabic gum, lactose, gelatine, magnesium stearate, corn starch, aqueous or non-aqueous vehicles, polyvinyl pyrolidone, semi-synthetic glycerides of fatty acids, benzalconium chloride, sodium phosphate, EDTA, polysorbate 80. The compositions- are advantageously formulated in doseage units each doseage unit being adapted to supply a single dose of the active ingredient. The dosis range applicable per day is between 0.1 mg to 1000mg, preferably between 1.0mg and 900mg, more preferably between 10mg and 800mg.
Each doseage unit may conveniently contain from 0.25mg to 300mg, preferably 1 mg to 200mg.
Suitable tablets may be obtained, for example, by mixing the active substances with known excipients, for example inert diluents such as calcium carbonate, calcium phosphate, or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatine, lubricants such as magnesium stearate or talc and / oragents for delaying release such as carboxymethyl cellulose, cellulose acetate phthalate or polyvinyl acetate. The tablets may also comprise several layers.
Coated tablets may be prepared accordingly by coating cores produced analogously to the tablets with substances normally used for tablet coatings, for example collidone or shellack, gum arabic, talc , titanium dioxide or sugar.
To achieve delayed release or prevent incompatibilities the core may also consist of a number of layers to achieve the delayed release, possibly using the excipients mentioned above for the tablets.
Syrups or elixirs containing the active substances or combinations thereof according to the invention may additionally contain a sweetener such as saccharin, cyclamate, glycerol or sugar and a flavour enhancer eg
of a flavouring such as vanilla or orange extract. They may also contain suspension adjuvants or thickeners such as sodium carboxymethyl cellulose, wetting agents such as, for example, condensation products of fatty alcohols
with ethylene oxide, or preservatives such as p-hydroxybenzoates.
Solutions for injection are prepared in the usual way e.g. with the addition of
preservatives such as p-hydroxybenzoates or stabilisers such as alkali metal saltsof ethylenediamine tetra acetic acid, and transferred to into injection vials or ampoules.
Capsules containing one or more active substances may for example be prepared by mixing the active substances with inert carriers such as lactose or sorbitol and packing them into gelatine capsules.
Suitable suppositories may be made for example by mixing with carriers provided this purpose, such as neutral fats or polyethyleneglycol or the derivatives thereof.
The examples which follow illustrate the present invention without restricting its scope. EXAMPLES OF PHARMACEUTICAL FORMULATIONS
Tablets Per Tablet
Bupropion Hcl 200 mg
Lactose 240 mg
Corn Starch 340 mg
Polyvinylpyrrolidone 45 mg
Magnesium Stearate 15 mg
Total 840 mg
The finely ground active substance, lactose and some of the corn starch are mixed together. The mixture is screened, then moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet-granulated and dried.
The granules, the remaining corn starch and the magnesium stearate are screened and mixed together. The mixture is compressed to produce tablets of a suitable shape and size.
TABLETS 2 PER TABLET
Bupropion Hcl 100 mg
Corn starch 190 mg
Lactose 55 mg
Microcrystalline Cellulose 35 mg
Polyvinylpyrrolidone 15 mg
Sodium carboxymethyl starch 23 mg
Magnesium stearate 2 mg
Total 420 mg
The finely ground active substance, some of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is screened and workedwith the remaining corn starch and water to form a granulate which is dried and screened. The sodium carboxymethyl starch and the magnesium stearate are added and mixed inand the mixture is compressed to form tablets of a suitable size. Coated Tablets Per Tablet
Bupropion Hcl 50 mg
Lactose 200 mg
Corn Starch 230 mg
Polyvinylpyrrolidone 10 mg
Magnesium Stearate 5 mg
Total 495 mg
The active substance, corn starch, lactose, and polyvinylpyrrolidone are thoroughly mixed and moistened with water. The moist mass is pushed through a screenwith a 1mm mesh size, dried at 45 degrees C and the granules are then passed through the same screen. After the magnesium stearate has been mixed in, convextablet cores with a diameter of 6mm are compressed in a tablet-making machine. The tablet cores thus produced are coated in known manner with a covering consisting of sugar and talc. The finished coated tablets are polished with wax.
CAPSULES Per Capsule
BUPROPION Hcl 150 mg
Corn starch 248.5 mg
Magnesium Stearate 1.5 mg
Total 400 mg
The substance and corn starch are mixed and moistened with water. The moist mass is screened and dried. The dry granules are screened and mixed withmagnesium stearate. The finished mixture is packed into size 1 hard gelatine capsules.
AMPOULE SOLUTION
BUPROPION HCL 200 mg
Sodium Chloride 200 mg
Water for injection 20 mg
The active substance is dissolved in water at its own pH or optionally at pH 5.5 -6.5 and sodium chloride is added to make it isotonic. The solution obtained is filtered free from pyrogens and the filtrate is transferred under
aseptic conditions into ampoules which are then sterilised and sealed by fusion. SUPPOSITORIES
BUPROPION HCL 300 mg
Solid fat 1650 mg
Total 1950 mg
The hard fat is melted. At 40 degrees C the ground active substance is homogenously dispersed. It is cooled to 38 degrees C and poured into slightly chilled suppository moulds.

Claims

1 A method of increasing sexual desire comprising: a Selection of a patient exhibiting symptoms of hypoactive sexual desire disorder, and b Administering a therapeutically effective amount of BUPROPION or a
pharmaceutically acceptable acid addition salt thereof
to the patient.
2 The method of claim 1 , wherein the patient exhibits deficient sexual fantasies.
3 The method of claim 1 , wherein the patient exhibits deficient desire for sexual activity.
4 The method of claim 1 , wherein the patient exhibits marked distress about the symptoms of hypoactive sexual desire disorder.
5 The method of claim 1 , wherein the patient exhibits a lack of responsive desire.
6 The method of claim 1 , wherein the patient is female.
7 The method of claim 1 , wherein the patient is male.
8 A method of increasing sexual desire comprising:
a Selecting a patient having decreased sexual desire, and
b administering a therapeutically effective amount of BUPROPION or a
pharmaceutically acceptable acid addition salt thereof to the patient.
9 A method of increasing sexual desire, and
a Selecting a patient having absent sexual desire, and
b Administering a therapeutically effective amount of BUPROPION or a
pharmaceutically acceptable acid addition salt thereof to the patient.
10. A method of increasing sexual desire, and
a Selecting a patient having inhibited sexual desire, and
b Administering a therapeutically effective amount of BUPROPION or a
pharmaceutically acceptable acid addition salt thereof to the patient.
1 1 . A method of increasing sexual desire comprising: a Diagnosing a patient with hypoactive sexual desire disorder, and
b Administering a therapeutically effective amount of BUPROPION or a
pharmaceutically acceptable acid addition salt thereof to the patient.
********************************** ******************************************************
PCT/GB2010/001649 2010-09-01 2010-09-01 Use of bupropion in treating sexual dysfunction WO2012028834A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/GB2010/001649 WO2012028834A1 (en) 2010-09-01 2010-09-01 Use of bupropion in treating sexual dysfunction

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/GB2010/001649 WO2012028834A1 (en) 2010-09-01 2010-09-01 Use of bupropion in treating sexual dysfunction

Publications (1)

Publication Number Publication Date
WO2012028834A1 true WO2012028834A1 (en) 2012-03-08

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001062257A2 (en) * 2000-02-22 2001-08-30 Sepracor Inc. Bupropion metabolites and methods of their synthesis and use
US20050096311A1 (en) * 2003-10-30 2005-05-05 Cns Response Compositions and methods for treatment of nervous system disorders
WO2007006738A2 (en) * 2005-07-12 2007-01-18 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising 2 , 3-disubstituted tropanes for the treatment of disorders of sexual desire
US20070203231A1 (en) * 2005-10-14 2007-08-30 Forest Laboratories, Inc. Methods of treating central nervous system disorders with a low dose combination of escitalopram and bupropion
US20100143256A1 (en) * 2001-07-11 2010-06-10 Cns Response, Inc. Electroencephalography based systems and methods for selecting therapies and predicting outcomes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001062257A2 (en) * 2000-02-22 2001-08-30 Sepracor Inc. Bupropion metabolites and methods of their synthesis and use
US20100143256A1 (en) * 2001-07-11 2010-06-10 Cns Response, Inc. Electroencephalography based systems and methods for selecting therapies and predicting outcomes
US20050096311A1 (en) * 2003-10-30 2005-05-05 Cns Response Compositions and methods for treatment of nervous system disorders
WO2007006738A2 (en) * 2005-07-12 2007-01-18 Boehringer Ingelheim International Gmbh Pharmaceutical composition comprising 2 , 3-disubstituted tropanes for the treatment of disorders of sexual desire
US20070203231A1 (en) * 2005-10-14 2007-08-30 Forest Laboratories, Inc. Methods of treating central nervous system disorders with a low dose combination of escitalopram and bupropion

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ASHTON A K ET AL: "BUPROPION AS AN ANTIDOTE FOR SEROTONIN REUPTAKE INHIBITOR-INDUCED SEXUAL DYSFUNCTION", JOURNAL OF CLINICAL PSYCHIATRY, PHYSICIANS POSTGRADUATE PRESS, INC, US, vol. 59, no. 3, 1 January 1998 (1998-01-01), pages 112 - 115, XP009074758, ISSN: 0160-6689 *
GINZBURG REGINA ET AL: "EFFECT OF BUPROPION ON SEXUAL DYSFUNCTION", ANNALS OF PHARMACOTHERAPY, HARVEY WHITNEY BOOKS COMPANY, vol. 39, no. 12, 1 January 2005 (2005-01-01), pages 2096 - 2099, XP009074744, ISSN: 1060-0280, DOI: DOI:10.1345/APH.1G275 *
LABBATE L A: "BUPROPION-SR-INDUCED INCREASED LIBIDO AND SPONTANEOUS ORGASM", CANADIAN JOURNAL OF PSYCHIATRY. REVUE CANADIENNE DEPSYCHIATRIE, CANADIAN PSYCHIATRIC ASSOCIATION, OTTAWA, CA, vol. 43, no. 5, 1 August 1998 (1998-08-01), pages 644/645, XP000972458, ISSN: 0706-7437 *
SEGRAVES ROBERT TAYLOR ET AL: "Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women", JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY, vol. 24, no. 3, June 2004 (2004-06-01), pages 339 - 342, XP009147325, ISSN: 0271-0749 *

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