WO2005094827A1 - Methodes de traitement d'un dysfonctionnement sexuel - Google Patents

Methodes de traitement d'un dysfonctionnement sexuel Download PDF

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Publication number
WO2005094827A1
WO2005094827A1 PCT/CA2004/000479 CA2004000479W WO2005094827A1 WO 2005094827 A1 WO2005094827 A1 WO 2005094827A1 CA 2004000479 W CA2004000479 W CA 2004000479W WO 2005094827 A1 WO2005094827 A1 WO 2005094827A1
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WO
WIPO (PCT)
Prior art keywords
sexual
disorder
dysfunction
sexual desire
receptor
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Application number
PCT/CA2004/000479
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English (en)
Inventor
Kenneth R. Evans
Terrence L. Sills
Albert Agro
Bruce Dzyngel
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Kestrel Pharmaceuticals Inc.
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Publication date
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Priority to PCT/CA2004/000479 priority Critical patent/WO2005094827A1/fr
Publication of WO2005094827A1 publication Critical patent/WO2005094827A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/536—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine

Definitions

  • the present invention provides methods for treating female hypoactive sexual desire disorder, the methods comprising the step of administering to a female patient in need thereof a therapeutically effective amount of a compound that is a selective agonist at the 5-HTlA receptor.
  • the above methods can be used to treat other sexual disorders in females, including (but not limited to) arousal disorder and orgasmic disorder.
  • the above methods can be used to treat male sexual dysfunction, including disorders of desire, arousal, and orgasm.
  • FHSDD Male Hypoactive Sexual Desire Disorder
  • SDD Sexual Desire Disorder
  • SDD Sexual Desire Disorder
  • Low or absent sexual desire is highly prevalent, being observed in greater than half of the females that report sexual dysfunction (Laumann et al . , 1999).
  • FHSDD may be lifelong or acquired, and be either a generalized (global) loss of desire or a situational (partner- specific) loss of desire.
  • the serotonin 1A (5-HT ⁇ A ) receptor may have a role in sexual behaviour.
  • stimulation of the 5HT ⁇ A receptor facilitates sexual behaviour in animals (Everaerd and Laan, 2000) .
  • the 5-HT 1A receptor agonists gepirone and ipsapirone facilitate lordosis in estrogen- treated female rodents (Mendelson and Gorzalka, 1986) .
  • the 5-HT ⁇ A agonist gepirone (CINP 2002) and the mixed 5-HT iA agonist/5-HT 2A antagonist flibanserin US patent application 20030104980A1 have both been shown to have prosexual effects, particularly enhancing sexual desire.
  • Prozac a serotonin reuptake inhibitor that enhances availability of serotonin, thereby increasing stimulation of the 5HT iA receptor
  • Prozac has been reported to cause spontaneous orgasm (Modell, 1989) as well as causing other hypersexual effects in some patients (Balon, 1994) .
  • the present invention is based upon the evidence set out above which indicates that drugs that stimulate the 5HT iA receptor have prosexual effects .
  • the present invention is therefore directed to a method for treating sexual dysfunction comprising administering to a patient in need thereof a therapeutically effective amount of a compound that is a selective agonist at the 5-HT 1A receptor.
  • An aspect of the invention relates to the use of a therapeutically effective amount of the compound that is a selective agonist at the 5-HT ⁇ A receptor for treating sexual dysfunction.
  • Another aspect of the invention relates to the use of a therapeutically effective amount of a compound that is a selective agonist at the 5-HT ⁇ A receptor for the preparation of a medicament for the treatment of sexual dysfunction.
  • the sexual dysfunction is female hypoactive sexual desire disorder.
  • the present invention relates to the use of a selective agonist at the 5-HT 1A receptor for treating sexual dysfunction.
  • the selective agonist at the 5-HT iA receptor is for treating female sexual dysfunction.
  • the female sexual dysfunction includes Hypoactive Sexual Desire Disorder, Sexual Arousal Disorder, Failure of Genital Response, or Orgasmic Disorder/Dysfunction.
  • the female sexual dysfunction is Hypoactive Sexual Desire disorder characterized by, but not limited to, loss of sexual desire, lack of sexual desire, decreased sexual desire, inhibited sexual desire, loss of libido, libido disturbance or frigidity.
  • the selective agonist at the 5-HT 1A receptor are those compounds which have activity substantially only against the 5-HT ⁇ A receptor.
  • the selective agonist at the 5-HT iA receptor are preferably selected from ipsapirone, tandospirone, eptapirone, lesopitron, repinotan, buspirone, flesinoxan, gepirone, alnespirone, VML-670,
  • 5-HT 1A receptor agonists are ipsapirone or repinotan.
  • the 5-HT ⁇ A receptor agonists can optionally be used in the form of their pharmaceutically acceptable acid addition salts.
  • Suitable acid addition salts include those of the acid selected from succinic acid, hydrobromide acid acetic acid fumaric acid maleic acid methane sulfonic acid lactic acid phosphoric acid hydrochloric acid sulfuric acid tartaric acid and citric acid. Mixtures of the acid addition salts may also be used.
  • the selective agonist at the 5-HT iA receptor optionally in the form of pharmaceutical acceptable acid addition salts may be incorporated into conventional pharmaceutical preparations in solid, liquid or spray forms.
  • the composition may be presented in the form suitable for oral, rectal, parenteral administration or for nasal inhalation. . These forms may include for example capsules, tablets, coated tablets, ampoules, suppositories and nasal spray.
  • the preferred forms are those for oral administration including capsules, tablets, coated tablets and extended release formulations.
  • the selective agonist at the 5-HT 1A receptor is incorporated in excipients or carriers conventionally used in pharmaceutical compositions such as, for example, talc, arabic gum, lactose, gelatin, magnesium stearate, cornstarch, aqueous or nonaqueous vehicles, polyvinyl pyrrolidone, semi synthetic glycerides of fatty acids, benzalconium chloride, sodium phosphate, EDTA, and polysorbate 80 among others.
  • the compositions are formulated in dosage units, each dosage unit being preferably adapted to supply a single dose of the active ingredient.
  • the dosage range applicable per day will vary depending upon the selective agonist at the 5-HT ⁇ A receptor but in general will be between 0.1 and 200 mg, more preferably between 0.5 and 160 mg.
  • Suitable tablets may be obtained, for example, by mixing the active substance (s) 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/or agents 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/or agents for delaying release, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate.
  • excipients for example inert dilu
  • Coated tablets may be prepared by coating cores produced analogously to the tablets with substances normally used for tablet coatings, for example collidone or shellac, gum arable, talc, titanium dioxide or sugar.
  • the core may also consist of a number of layers.
  • the tablet coating may consist of a number or layers to achieve 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 saccharine, cyclamate, glycerol or sugar and a flavour enhancer, e.g. 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 .
  • a sweetener such as saccharine, cyclamate, glycerol or sugar
  • a flavour enhancer e.g. a 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 with ethylene oxide, or preservatives such as p- hydroxybenzoates .
  • Solutions for injection are prepared in the usual way, with the addition of preservatives such as p- hydroxybenzoates, or stabilizers such as alkali metal salts of ethylenediamine tetraacetic acid, and transferred into injection vials or ampoules.
  • Capsules containing one or more active substances or combinations of 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 for this purpose, such as neutral fats or polyethylene glycol or the derivatives thereof.
  • the 5-HTi a agonists are preferably selected from ipsapirone, tandospirone, eptapirone, lesopitron, repinotan, buspirone, flesinoxan, gepirone, alnespirone, VML-670, MKC 242, OPC-14523, S-15535, and SUN N4057.
  • Ipsapirone is a 5-HTlA agonist developed by Bayer and is used at a dosage of 5 to 30 mg per day.
  • Tandospirone has been developed by Sumitomo and is used at a dosage of 5 to 160 mg per day.
  • Eptapirone is a 5-HT ⁇ a agonist developed by Pierre Fabre and is used at a dosage of 1 to 10 mg per day.
  • Lesopitron is a 5-HT ⁇ a agonist developed by Esteve and is used at a dosage of 5 to 80 mg per day.
  • Repinotan is a 5-HT la agonist developed by Bayer and is used at a dosage of 0.5 to 10 mg per day.
  • Buspirone is a 5-HT ⁇ a agonist developed by Bristol-Meyers Squibb and is used at a dosage of 10 to 60 mg per day.
  • Flesinoxan is a 5-HT ⁇ a agonist developed by Solvay and is used at a dosage of 1 to 10 mg per day.
  • Gepirone is a 5-HT la agonist developed by Organon and is used at a dosage of 10 to 80 mg per day.
  • the medicaments according to the invention in general contain 1 to 15% by weight, preferably 5 to 10% by weight, of 2-pyrimidinyl-l-piperazine derivatives.
  • medicaments according to the invention contain further active compounds known per se.
  • the medicaments according to the invention may be converted in a known manner into the customary formulations, such as tablets, dragees, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert, non-toxic, pharmaceutically suitable excipients or solvents.
  • the formulations are produced, for example, by extending the active compounds with solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, where, for example, in the case of the use of water as a diluent, organic solvents may be used if appropriate as auxi1iary so1vents .
  • Auxiliaries which may be mentioned are, for example: water, non-toxic organic solvents, such as paraffins (for example mineral oil fractions) , vegetable oils (for example groundnut/sesame oil) , alcohols (for example ethyl alcohol, glycerol) , excipients, such as, for example, ground natural minerals (for example kaolins, clays, talc, chalk) , ground synthetic minerals (for example highly disperse silica, silicates) , sugars (for example sucrose, lactose and dextrose) , emulsifiers (for example polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, alkylsulphonates and arylsulphonates) , dispersants (for example lignin, sulphite waste liquors, methylcellulose, starch and polyvinylpyrrolidone) and lubricants (for example magnesium stearate, talc, stearic acid and sodium la
  • tablets may of course also contain additives, such as sodium citrate, calcium carbonate and dicalcium phosphate together with various additives, such as starch, preferably potato starch, gelatin and the like in addition to the said excipients.
  • additives such as sodium citrate, calcium carbonate and dicalcium phosphate together with various additives, such as starch, preferably potato starch, gelatin and the like in addition to the said excipients.
  • lubricants such as magnesium stearate, sodium lauryl sulphate and talc may additionally be used for tabletting.
  • various flavor-improvers or colorants may be added to the active compounds in addition to the above entioned auxiliaries.
  • Physiologically acceptable salts of the compounds used according to the invention can be salts of the compounds with mineral acids, carboxylic acids or sulphonic acids.
  • Particularly preferred salts are those, for example, with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid, benzenesulphonic acid, naphthalenedisulphonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, oxalic acid, citric acid, fumaric acid, maleic acid or benzoic acid.
  • Hydrates within the meaning of the invention are stoichiometric compositions of 2- [4 ( ⁇ [ (2R) -8-isopropoxy- chroman-2-yl]methyl ⁇ amino) butyl] -1, 2-benzisothiazol- 3(2H)-one 1,1-dioxide or its salts with water.
  • Solvates within the meaning of the invention are stoichiometric compositions of 2- [4- ( ⁇ [ (2R) -8-isopropoxy- chroman-2-yl] ethyl ⁇ amino)butyl- ] -1, 2-benzisothiazol- 3(2H)-one 1,1-dioxide or its salts with solvents.
  • the compounds used according to the invention can be prepared by the processes specified in EP-A-0 749 970.
  • 2- [4- ( ⁇ [ (2R) -8-isopropoxy-chroman-2- yl]methyl ⁇ amino)butyl] -1, 2-benzisothi- azol-3 (2H) -one 1,1-dioxide hydrochloride is prepared according to Example 7 in EP-A-0 749 970.
  • the salts of 2- [4- ( ⁇ [ (2R) -8-isopropoxy-chroman-2- yl]methyl ⁇ amino) butyl] -1, 2-benz-isothiazol-3 (2H) -one 1, 1- dioxide can be obtained by reacting the free base in a suitable solvent with stoichiometric or superstoichiometric amounts of the acid on which the salt is based in a temperature range from 0°C. up to the boiling point of the solvent.
  • Suitable solvents are, for example, water, aliphatic alcohols such as ethanol, ethanol or 2-propanol, aliphatic open-chain or cyclic ethers such as diethyl ether, tert-butyl methyl ether, dioxane, tetrahydrofuran or , aliphatic ketones such as 2- propanone, 2-butanone, and their mixtures.
  • the salts are obtained directly from this mixture, if appropriate after partially or completely distilling off the solvent, as a solid; they can be purified by recrystallization or reprecipitation in, for example, the abovementioned solvents or their mixtures .
  • the active compound can act systemically and/or locally.
  • it can be administered in a suitable manner, such as, for example, orally, parenterally, pulmonarily, nasally, sublingually, lingually, buccally, rectally, transdermally, conjunctivally, otically or as an implant. Administration is preferably carried out orally.
  • the active compound can be administered in suitable administration forms.
  • suitable administration forms which release the active compound rapidly and/or in modified form, such as, for example, tablets (non-coated and coated tablets, e.g. enteric coatings) , capsules, sugar-coated tablets, granules, pellets, powders, emulsions, suspensions and solutions.
  • Parenteral administration can be carried out with avoidance of an absorption step (intravenous, intraarterial, intracardiac, intraspinal or intralumbar) or with inclusion of an absorption (intramuscular, subcutaneous, intracutaneous, percutaneous or intraperitoneal) .
  • Suitable administration forms for parenteral administration are, inter alia, injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilizates and sterile powders .
  • Forms suitable for other administration routes are, for example, inhalatory pharmaceutical forms (inter alia powder inhalers, nebulizers), nasal drops/solutions, sprays; tablets or capsules to be administered lingually, sublingually or buccally, suppositories, ear and eye preparations, vaginal capsules, aqueous suspensions (lotions, shake mixtures) , lipophilic suspensions, ointments, creams, milk, pastes, dusting powder or implants .
  • inhalatory pharmaceutical forms inter alia powder inhalers, nebulizers
  • nasal drops/solutions, sprays tablets or capsules to be administered lingually, sublingually or buccally, suppositories, ear and eye preparations, vaginal capsules, aqueous suspensions (lotions, shake mixtures) , lipophilic suspensions, ointments, creams, milk, pastes, dusting powder or implants .
  • the active compounds can be converted into the administration forms mentioned in a manner per se known. This is carried out using inert non-toxic, pharmaceutically suitable excipients.
  • vehicles e.g. microcrystalline cellulose
  • solvents e.g. liquid polyethylene glycols
  • emulsifiers e.g. sodium dodecyl sulphate
  • dispersing agents e.g. polyvinylpyrrolidone
  • synthetic and natural biopolymers e.g. albumin
  • stabilizers e.g. antioxidants such as ascorbic acid
  • colourants e.g. inorganic pigments such as iron oxides
  • taste and/or odour corrigents e.g. inert non-toxic, pharmaceutically suitable excipients.
  • inert non-toxic, pharmaceutically suitable excipients include, inter alia, vehicles (e.g. microcrystalline cellulose), solvents (e.g. liquid polyethylene glycols) , emulsifiers (e.
  • the other selective agonists at the 5-HT 1A receptor may be formulated and used in the present invention.
  • tandospirone 3a alpha, 4 beta, 7 beta, 7a alpha- hexahydro-2- (4- (4- (2-pyrimidinyl) -1- piperazinyl) -butyl) -

Abstract

L'invention concerne des méthodes de traitement d'une baisse du désir sexuel, qui comprennent l'étape consistant à administrer à un patient nécessitant un tel traitement une quantité thérapeutiquement efficace d'un composé constituant un agoniste sélectif du récepteur 5-HT1A. Lesdites méthodes peuvent servir à traiter d'autres troubles sexuels féminins, notamment (mais pas exclusivement) des troubles de l'excitation et de l'orgasme. Ces méthodes peuvent éventuellement servir à traiter un dysfonctionnement sexuel masculin, y compris des troubles du désir, de l'excitation et de l'orgasme.
PCT/CA2004/000479 2004-03-30 2004-03-30 Methodes de traitement d'un dysfonctionnement sexuel WO2005094827A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008054215A2 (fr) * 2006-11-03 2008-05-08 Emotional Brain B.V. Utilisation de 3-alpha-androstanediol, eventuellement en combinaison avec un agoniste 5-ht1a, dans le traitement du dysfonctionnement sexuel
WO2009082268A2 (fr) 2007-12-21 2009-07-02 Alla Chem, Llc Ligands dalpha-adrénorécepteurs, de récepteurs de dopamine, de l'histamine, d'imidazoline et de sérotonine ainsi que leurs procédés d'utilisation
US9192669B2 (en) 2004-05-11 2015-11-24 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US9333203B2 (en) 2005-11-11 2016-05-10 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction

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US9192669B2 (en) 2004-05-11 2015-11-24 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US10441592B2 (en) 2004-05-11 2019-10-15 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US9700566B2 (en) 2004-05-11 2017-07-11 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US9737548B2 (en) 2005-11-11 2017-08-22 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US9333203B2 (en) 2005-11-11 2016-05-10 Eb Ip Lybrido B.V. Pharmaceutical formulations and uses thereof in the treatment of female sexual dysfunction
US9211334B2 (en) 2006-11-03 2015-12-15 Eb Ip Lybridos B.V. Use of testosterone and a 5-HT1A agonist in the treatment of sexual dysfunction
WO2008054215A3 (fr) * 2006-11-03 2009-04-09 Emotional Brain Bv Utilisation de 3-alpha-androstanediol, eventuellement en combinaison avec un agoniste 5-ht1a, dans le traitement du dysfonctionnement sexuel
US8575139B2 (en) 2006-11-03 2013-11-05 Emotional Brain B.V. Use of testosterone and a 5-HT1a agonist in the treatment of sexual dysfunction
US8648060B2 (en) 2006-11-03 2014-02-11 Emotional Brain B.V. Use of 3-alpha-androstanediol in combination with a 5-HT1a agonist, in the treatment of sexual dysfunction
US8653051B2 (en) 2006-11-03 2014-02-18 Emotional Brain B.V. Use of 3-alpha-androstanediol in combination with a PDE5 inhibitor, in the treatment of sexual dysfunction
US8669242B2 (en) 2006-11-03 2014-03-11 Emotional Brain B.V. Use of testosterone and a 5-HT1A agonist in the treatment of sexual dysfunction
JP2014111608A (ja) * 2006-11-03 2014-06-19 Emotional Medical Bv 性機能不全の治療における、任意で５−ＨＴ１ａアゴニストと組み合わせた、３−α−アンドロスタンジオールの使用
JP2015157849A (ja) * 2006-11-03 2015-09-03 イービー アイピー ライブリドス ビー．ブイ． 性機能不全の治療におけるテストステロンおよび５−ｈｔ１ａアゴニストの使用
EP2937086A1 (fr) * 2006-11-03 2015-10-28 EB IP Lybridos B.V. Utilisation de testostérone et d'un agoniste de la 5-ht1a pour le traitement de dysfonctionnement sexuel
WO2008054213A2 (fr) * 2006-11-03 2008-05-08 Emotional Brain B.V. Utilisation de testostérone et d'un agoniste de la 5-ht1a dans le traitement d'un dysfonctionnement sexuel
WO2008054215A2 (fr) * 2006-11-03 2008-05-08 Emotional Brain B.V. Utilisation de 3-alpha-androstanediol, eventuellement en combinaison avec un agoniste 5-ht1a, dans le traitement du dysfonctionnement sexuel
WO2008054213A3 (fr) * 2006-11-03 2009-04-09 Emotional Brain Bv Utilisation de testostérone et d'un agoniste de la 5-ht1a dans le traitement d'un dysfonctionnement sexuel
US9597335B2 (en) 2006-11-03 2017-03-21 Eb Ip Lybridos B.V. Use of testosterone and a 5-HT1A agonist in the treatment of sexual dysfunction
JP2010509211A (ja) * 2006-11-03 2010-03-25 エモーショナル ブレイン ビー．ブイ． 性機能不全の治療におけるテストステロンおよび５−ｈｔ１ａアゴニストの使用
JP2017132809A (ja) * 2006-11-03 2017-08-03 イービー アイピー ライブリドス ビー．ブイ． 性機能不全の治療におけるテストステロンおよび５−ｈｔ１ａアゴニストの使用
EP1925307A1 (fr) * 2006-11-03 2008-05-28 Emotional Brain B.V. Utilisation de 3-alpha-androstanediol pour le traitement des dysfonctions sexuelles
US10314848B2 (en) 2006-11-03 2019-06-11 Eb Ip Lybridos B.V. Use of testosterone and a 5-HT1A agonist in the treatment of sexual dysfunction
WO2009082268A2 (fr) 2007-12-21 2009-07-02 Alla Chem, Llc Ligands dalpha-adrénorécepteurs, de récepteurs de dopamine, de l'histamine, d'imidazoline et de sérotonine ainsi que leurs procédés d'utilisation

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