CN101495109A - Pharmaceutical composition comprising, in combination, saredutant and a selective serotonin reuptake inhibitor or a serotonin/norepinephrine reuptake inhibitor - Google Patents
Pharmaceutical composition comprising, in combination, saredutant and a selective serotonin reuptake inhibitor or a serotonin/norepinephrine reuptake inhibitor Download PDFInfo
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- CN101495109A CN101495109A CNA2007800287391A CN200780028739A CN101495109A CN 101495109 A CN101495109 A CN 101495109A CN A2007800287391 A CNA2007800287391 A CN A2007800287391A CN 200780028739 A CN200780028739 A CN 200780028739A CN 101495109 A CN101495109 A CN 101495109A
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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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
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- 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
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Abstract
A subject-matter of the present invention is pharmaceutical compositions comprising, in combination, at least one active ingredient chosen from (S)-(-)-N-[4-(4-acetamido-4-phenylpiperidin-1-yl)-2-(3,4-dichlorophenyl)butyl]-N-methylbenzamide and pharmaceutically acceptable salts there and at least one second active ingredient chosen from selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors and pharmaceutically acceptable salts thereof.
Description
The objective of the invention is pharmaceutical composition, it comprises (S)-(-)-N-[4-(4-acetylaminohydroxyphenylarsonic acid 4-Phenylpiperidine-1-yl)-2-(3, the 4-Dichlorobenzene base) butyl]-selective depressant of a kind of and 5-hydroxy tryptamine (serotonine) reuptake (recapture) of N-methyl-benzamide or its officinal salt or with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine (nor é pinephrine) reuptake.
Its international saredutant by name (saredutant) have a formula:
(S)-(-)-N-[4-(4-acetylaminohydroxyphenylarsonic acid 4-Phenylpiperidine-1-yl)-2-(3, the 4-Dichlorobenzene base) butyl]-N-methyl-benzamide (below be called compd A) and its officinal salt be described to the NK of neurokinin A
2The selectivity non-peptide antagonist of the brute force of receptor (Life Sciences, 1992,50 (15), PL 101-PL 106) also can prepare according to patent EP 0 474 561 or US 5 236 921.
Above-mentioned salt is and the pharmaceutically useful inorganic or organic acid salt of routine, for example hydrochlorate, hydrobromate, sulfate, disulfate, dihydric phosphate, methane sulfonates, Methylsulfate, acetate, oxalates, maleate, fumarate, succinate, naphthalene-2-sulfonic acid salt, glycinate (glyconate), gluconate, citrate, isethionate, benzene sulfonate or tosilate.
Term " selective depressant of serotonin reuptake transporter " (SSRI) can be regarded as the following chemical compound of expression, for example:
-(scholar)-N-methyl-3-phenyl-3-[4-(trifluoromethyl) phenoxy group] propane-1-amine, its international fluoxetine by name (fluoxetine) has formula:
(below be called compd B) and its officinal salt, it can prepare according to patent US 4 314 081;
-1-[3-(dimethylamino) propyl group]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-nitrile, its international citalopram by name (citalopram) and its officinal salt, it can prepare according to patent US 4 136 193;
-S-(+)-1-[3-(dimethylamino) propyl group]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-nitrile, its international escitalopram by name (escitalopram) and its officinal salt, it can prepare according to patent EP 0 347 066 or US 4 943 590;
-anti--(-)-3-[(1,3-benzo dioxane penta ring (benzodioxol)-5-oxygen base) methyl]-4-(4-fluorophenyl) piperidines, its international paroxetine by name (paroxetine) and its officinal salt, it can prepare according to patent US 3 912 743 and US 4 007 196;
-(1S-is suitable)-4-(3, the 4-Dichlorobenzene base)-1,2,3,4-tetrahydrochysene-N-methyl isophthalic acid-naphthylamines, its international Sertraline by name (sertraline) and its officinal salt, it can prepare according to patent US 4 536 518;
-5-methoxyl group-1-[4-(trifluoromethyl) phenyl]-1-pentanone-O-(2-amino-ethyl) oxime, its international fluvoxamine by name (fluvoxamine) and its officinal salt, it can prepare according to patent US 4 085 225;
Term " inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake " (SNRI) can be regarded as the following chemical compound of expression, for example:
-1-[2-dimethylamino-1-(4-methoxyphenyl) ethyl] cyclohexane extraction-1-alcohol, its international venlafaxine by name (venlafaxine) and its officinal salt, it can prepare according to patent EP 0 112669;
-(+)-(S)-N-methyl-3-(1-naphthoxy)-3-(benzene sulfur-2-base (thiophen-2-yl)) propane-1-amine, its international duloxetine by name (duloxetine) and its officinal salt, it can prepare according to patent EP 0 273 658;
-(1R, 2R)-2-(amino methyl)-N, N-diethyl-1-benzyl ring propane-1-Methanamide, international midalcipran by name (milnacipran) and its officinal salt, it can prepare according to patent US 4,478 836;
Find surprisingly at present, the selective depressant of saredutant and serotonin reuptake transporter or pharmacological action, particularly antidepressant effect when having strengthened significantly with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake that these chemical compounds use separately separately.
Therefore, comprise above-mentioned bonded pharmaceutical composition can be used for the preparation be used for the prevention and the treatment affective disorders (trouble de l ' humeur), it is selected from major depressive disorder (trouble d é pressifmajeur), repellence depression (trouble d é pressif r é sistant), dysthymic disorder (troubledysthymique), non-specific depression (trouble d é pressif non sp é cifie), bipolar I type mental disorder (trouble bipolaire I), bipolar II type mental disorder (trouble bipolaire II), cycloophrenia obstacle (trouble cyclothymique), non-specific bipolarity mental disorder (trouble bipolaire non specifi é), the affective disorders that physical disease causes (troublede l ' humeur
à une affection m é dicale g é n é rale), the affective disorders (le trouble de l ' humeur induit par une substance) that brings out by material, non-specific affective disorders (le trouble de l ' humeur non sp é cifi é); Anxiety neurosis (troubles anx1eux), it is selected from stress state (é tat destress post-traumatique) after panic attack (attaque de panique), agoraphobia, social phobia (la phobiesociale), obsession (le trouble obsessionnel compulsif), the wound, acute stress state (l ' é tat de stress aigu), generalized anxiety disorder (le trouble anxieux g é n é ralis é) or the medicine of the anxiety neurosis of being brought out by material.
Especially, comprise above-mentioned bonded pharmaceutical composition and can be used for preparing the medicine that is used for preventing and treating major depressive disorder.
More particularly, comprise above-mentioned bonded pharmaceutical composition and can be used for preparing the medicine that is used for treating the relevant sexual dysfunction of major depressive disorder.
Term " sexual dysfunction " can be regarded as by Americanism medical association (AmericanPsychiatric Association)-DSM-IV-TR, Manuel diagnostique et statistiquedes troubles mentaux, the 4th edition, revised text (Washing DC, 2000), the defined any pathology of 617-654 page or leaf, and it comprises that dysaphrodisia (promptly, obstacle: libido descends, and obstacle: property detest), sexual arousal dysfunction (that is, female sexual arousal disorder and male erectile disorder), orgasm disorder (promptly, female orgasmic disorder, male orgasmic disorder and premature ejaculation), painful sexual dysfunction (that is, dyspareunia and vulvismus), the sexual dysfunction that physical disease causes, the sexual dysfunction and the non-specific sexual dysfunction that bring out by material.
Therefore, according to an one aspect, the objective of the invention is pharmaceutical composition, it comprise saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake, and at least a pharmaceutically useful excipient.
Especially, the objective of the invention is pharmaceutical composition, it comprises the coupling of selective depressant of a kind of and serotonin reuptake transporter of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises the coupling of selective depressant of a kind of of saredutant or its officinal salt and a kind of serotonin reuptake transporter that is selected from fluoxetine, citalopram, escitalopram, paroxetine, Sertraline and fluvoxamine or their officinal salts, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and fluoxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and citalopram or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and escitalopram or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and paroxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and Sertraline or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and fluvoxamine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises the coupling of inhibitor of a kind of and 5-hydroxy tryptamine/norepinephrine reuptake of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises the coupling of inhibitor of a kind of of saredutant or its officinal salt and a kind of 5-hydroxy tryptamine/norepinephrine reuptake that is selected from venlafaxine, duloxetine and midalcipran or their officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and venlafaxine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and duloxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
More particularly, the objective of the invention is pharmaceutical composition, it comprises a kind of coupling of a kind of and midalcipran or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
According to its another aspect, the objective of the invention is saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake.
Especially, the objective of the invention is the coupling of selective depressant of a kind of of saredutant or its officinal salt and a kind of serotonin reuptake transporter that is selected from fluoxetine, citalopram, escitalopram, paroxetine, Sertraline and fluvoxamine or their officinal salt.
More particularly, the objective of the invention is the coupling of inhibitor of a kind of of saredutant or its officinal salt and a kind of 5-hydroxy tryptamine/norepinephrine reuptake that is selected from venlafaxine, duloxetine and midalcipran or their officinal salt.
According to its another aspect, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprise saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with a kind of coupling of the inhibitor or their officinal salt of 5-hydroxy tryptamine/norepinephrine reuptake, described medicine is used for prevention and treatment affective disorders, it is selected from major depressive disorder, the repellence depression, the dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, the cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, by the affective disorders that material brings out, non-specific affective disorders; Anxiety neurosis, the anxiety neurosis that it is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or is brought out by material.
Especially, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprise saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with a kind of coupling of the inhibitor or their officinal salt of 5-hydroxy tryptamine/norepinephrine reuptake, described medicine is used for prevention and treatment major depressive disorder.
More particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprise saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with a kind of coupling of the inhibitor or their officinal salt of 5-hydroxy tryptamine/norepinephrine reuptake, described medicine is used for the treatment of the relevant sexual dysfunction of major depressive disorder.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of and escitalopram (escitolopram) of saredutant or its officinal salt or a kind of coupling of its officinal salt, described medicine is used for prevention and treatment affective disorders, and it is selected from major depressive disorder, the repellence depression, the dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, the cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, the affective disorders that brings out by material, non-specific affective disorders; Anxiety neurosis, the anxiety neurosis that it is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or is brought out by material.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of and escitalopram (escitolopram) of saredutant or its officinal salt or a kind of coupling of its officinal salt, and described medicine is used for prevention and treatment major depressive disorder.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of and escitalopram (escitolopram) of saredutant or its officinal salt or a kind of coupling of its officinal salt, and described medicine is used for the treatment of the relevant sexual dysfunction of major depressive disorder.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of coupling of a kind of and paroxetine or its officinal salt of saredutant or its officinal salt, described medicine is used for prevention and treatment affective disorders, and it is selected from major depressive disorder, the repellence depression, the dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, the cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, the affective disorders that brings out by material, non-specific affective disorders; Anxiety neurosis, the anxiety neurosis that it is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or is brought out by material.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of coupling of a kind of and paroxetine or its officinal salt of saredutant or its officinal salt, and described medicine is used for prevention and treatment major depressive disorder.
Also more particularly, the objective of the invention is the purposes that pharmaceutical composition is used to prepare medicine, described pharmaceutical composition comprises a kind of coupling of a kind of and paroxetine or its officinal salt of saredutant or its officinal salt, and described medicine is used for the treatment of the relevant sexual dysfunction of major depressive disorder.
According to it on the other hand, the objective of the invention is saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with the purposes of a kind of coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake or their officinal salt, described medicine is used for prevention and treatment affective disorders, and it is selected from major depressive disorder, the repellence depression, the dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, the cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, the affective disorders that brings out by material, non-specific affective disorders; Anxiety neurosis, the anxiety neurosis that it is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or is brought out by material.
According to the medicament forms and the medication of expectation, in usual excipients well known by persons skilled in the art, select excipient.
In being used for oral, Sublingual, subcutaneous, intramuscular, intravenous, body surface, part, trachea, the pharmaceutical composition of the present invention of intranasal, percutaneous or rectally, active component can with the mixture of conventional pharmaceutical excipient, with the unit form of medication to the administration of animal and human's class, with prevention or treat above-mentioned obstacle or disease.
Suitable unit form of medication comprises oral form, as tablet, soft or hard capsule, powder, granule and oral administration solution or suspension, in the Sublingual, buccal, trachea, ophthalmic, the form of medication of intranasal by sucking, body surface, percutaneous, subcutaneous, intramuscular or intravenous administration form, rectally form and implant form.Use for body surface, chemical compound of the present invention can use in emulsifiable paste, gel, ointment or washing liquid.
In pharmaceutical composition of the present invention, described one or more active component are mixed with dosage unit usually.To administration every day, every day 1 time or repeatedly, every dosage unit comprises 2.5-500mg be 10-250mg advantageously, be preferably the every dosage unit of 10-150mg.Although these dosage are examples of average situation, also may there be special case, wherein, higher or lower dosage is suitable; These dosage are also contained among the present invention.According to common practice, the dosage that is fit to each patient is decided according to administering mode, described patient's age, body weight and reaction by the doctor.
According to a further aspect in the invention, compd A and other active component of the present invention can carry out administration simultaneously, separately or in time in batches.
Term " uses simultaneously " and can be regarded as the chemical compound that administration is contained in the compositions of the present invention in the single and identical medicament forms.
Term " uses separately " and can be regarded as two chemical compounds that are contained in the compositions of the present invention in the different medicament forms at identical time administration separately.
Term " uses in time in batches " and can be regarded as and represent that administration in succession is contained in first chemical compound of the compositions of the present invention in a kind of medicament forms, is contained in second chemical compound of the compositions of the present invention in the different pharmaceutical form then.
In situation of this " in time in batches use ", the interval between second chemical compound of first chemical compound of administration compositions of the present invention and administration same compositions of the present invention generally is no more than 24 hours.
Unit medicament forms or comprise component cpd single a kind of of compositions of the present invention or comprise the coupling of 2 kinds of chemical compounds, it can be used in the above-mentioned all kinds of purposes, for example, is applicable to oral, intranasal, parenteral or percutaneous dosing.
Thereby in the situation of " using separately " and " in batches using in time ", two kinds of different medicament forms can be used for identical route of administration or different route of administration (oral and percutaneous or oral and intranasal or parenteral or percutaneous etc.).
Therefore, the invention still further relates to the test kit (trousse) that comprises compd A of the present invention and other active component, wherein, compd A of the present invention and other active component are arranged in chamber separately, and be in the identical or different packing, and be used for carrying out simultaneously, separately or in time administration in batches.
Especially, and indefiniteness ground, the enhancing according to the pharmacological effect of the coupling of compd A of the present invention and fluoxetine (compd B) is proved to be in animal.
Also more particularly, study in clinical research according to the effect of the coupling of the selective depressant of compd A of the present invention and serotonin reuptake transporter.
Embodiment 1
According to people such as C.Louis, Neuropsychopharmacology, 2006, the technology of 1-8 record is used rat in vivo test DRL-72s (low speed rate variance formula is strengthened 72 seconds programs (Differential Reinforcement of Low-rate-72seconds)).
At independent compd A, after the intraperitoneal administration of compd B and binding compounds A+ compd B, award (r é compense) (compression number of increase) percentage ratio and the contrast (separately solvent) total with respect to rat compression number (appuis) of acquisition compared separately.
In the DRL-72s test, measured the minimum effective dose of independent compd A and independent compd B in advance, that is:
-compd A: intraperitoneal administration 10mg/kg;
-compd B: intraperitoneal administration 5mg/kg.
For this research, select the independent compd A of weak effective dose and the independent compd B and the compd A+compd B of ineffective dose.
With the independent compd A of 3mg/kg dosage and the independent compd B of 2.5mg/kg dosage, be dissolved in and comprise 0.1% (v/v) Tween
0.9% (weight/volume) sodium-chloride water solution in, and carry out the intraperitoneal administration with the final volume of 1ml/kg.
In conjunction with administration by endoperitoneal compd A (3mg/kg) then twice of compd B (2.5mg/kg) administration simultaneously carry out.
Wherein the dosage of chemical compound is represented with free main component (base) form.
Because the needs of test, solvent (contrast) effect is compared, and every animal is measured the effect of independent compd A, the effect and the bonded effect of compd A+compd B of independent compd B.
Therefore, every rat (n=8) has been accepted 4 injections in time in batches, i.e. solvent (contrast), the coupling of compd A, independent compd B and compd A+compd B separately.
Gained the results are summarized in the Table I, and represents with respect to the percentage ratio of pushing sum with the award of duration of test (1 hour) gained, is expressed as the form of meansigma methods ± SEM (with respect to standard error of the mean).
*P＜0.05 is with respect to contrast
The gained result shows:
-with respect to controlled trial, seldom change the percent of gained award with the individually dosed compd A of 3mg/kg dosage; And this increase is not a statistically significant;
-with respect to controlled trial,, do not change the percent of gained award with the individually dosed compd B of 2.5mg/kg dosage;
-with respect to controlled trial, the coupling of compd A and compd B has improved the percent of gained award significantly, and this increase is a statistically significant.
Therefore, unexpectedly show its positive effect to the behavior of animal in this test according to the coupling of compd A of the present invention and compd B, this can confirm that this combination is used for the treatment of the antidepressant probability of application.
Embodiment 2
At the multicentricity that continued for 8 weeks at random in (multicentriques randomis é es) double blind clinical studies, evaluated and tested effect according to the coupling of saredutant of the present invention and escitalopram, wherein this research comprises the saredutant of accepting 1 fixed dosage every day group of escitalopram in conjunction with 1 fixed dosage every day, with accept saredutant placebo (placebo saredutant) in conjunction with the group of the escitalopram of fixed dosage with accept the other group of saredutant placebo in conjunction with the escitalopram placebo.
Carry out these clinical researches on one's body in the sex adult patients that shows major depressive disorder, described major depressive disorder is as passing through Diagnostic and Statistical Manuel of mentalDisorders, the 4th edition, the standard of revised text (DSM-IV-TR) defines, and by MiniInternational Neuropsychiatric Interview (MINI), people such as Lecrubier Y., Eur.Psychiatr., 1997
12, the standard of 224-231 confirms.
With respect to placebo group, measure the variation of overall score that last basis of observing between (being expected at the 56th day) and the first observed (before treatment begins) comprises 17 Hamilton depressive scale (HAM-D).Described Hamilton depressive scale passes through Hamilton M., J.Neurol.Neurosurg.Psychiatry, and 1960,
23, 56-62 defines.
With respect to placebo group, also measure the last variation of observing between (being expected at the 56th day) and the first observed (before treatment begins) of overall score that comprises 14 CSFQ (sexual function variation questionnaire).Described CSFQ passes through people such as Clayton AH, Psychopharmacol.Bull., and 1997,
33, 731-745 defines.
Embodiment 3
In the multicentricity randomized, double-blind clinical research that continued for 8 weeks, evaluated and tested effect according to the coupling of saredutant of the present invention and paroxetine, wherein this research comprises the saredutant of accepting 1 fixed dosage every day group of paroxetine in conjunction with 1 fixed dosage every day, with accept the saredutant placebo in conjunction with the group of the paroxetine of fixed dosage with accept the saredutant placebo and the other group of paroxetine placebo.
Showing on one's body the sex adult patients of major depressive disorder, these clinical researches have been carried out, described major depressive disorder is as passing through Diagnostic and Statistical Manuel ofMental Disorders, the 4th edition, the standard of revised text (DSM-IV-TR) defines, and by Mini International Neuropsychiatric Interview (MINI), people such as Lecrubier Y., Eur.Psychiatr., 1997
12, the standard of 224-231 confirms.
With respect to placebo group, measure the variation of overall score that last basis of observing between (being expected at the 56th day) and the first observed (before treatment begins) comprises 17 Hamilton depressive scale (HAM-D).Described Hamilton depressive scale passes through Hamilton M., J.Neurol.Neurosurg.Psychiatry, and 1960,
23, 56-62 defines.
With respect to placebo group, also measured the variation of overall score that comprises 14 CSFQ (sexual function variation questionnaire) between last observation (being expected at the 56th day) and the first observed (before treatment beginning).Described CSFQ is according to people such as Clayton AH, Psychopharmacol.Bull., and 1997,
33, 731-745 defines.
Embodiment 4: the capsule with 30mg saredutant
Saredutant (expression main component) 30.0mg
Lactose monohydrate (200 order) QSP 400.0mg
Cross-linking sodium carboxymethyl cellulose 8.0mg
Magnesium stearate 4.0mg
Purified water
*QS
No. 0 opaque capsule is filled to 400.0mg
*Behind wet granulation, be evaporated to drying.
Embodiment 5: the capsule with 100mg saredutant
Saredutant (expression main component) 100.0mg
Lactose monohydrate (200 order) QSP 400.0mg
Cross-linking sodium carboxymethyl cellulose 8.0mg
Magnesium stearate 4.0mg
Purified water
*QS
No. 0 opaque capsule is filled to 400.0mg
*Behind wet granulation, be evaporated to drying.
Claims (26)
1. pharmaceutical composition, it comprise saredutant or its officinal salt a kind of and serotonin reuptake transporter selective depressant or with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake, and at least a pharmaceutically useful excipient.
2. the described pharmaceutical composition of claim 1, it comprises the coupling of selective depressant of a kind of and serotonin reuptake transporter of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
3. claim 1 or 2 described pharmaceutical compositions, it comprises the coupling of selective depressant of a kind of of saredutant or its officinal salt and a kind of serotonin reuptake transporter that is selected from fluoxetine, citalopram, escitalopram, paroxetine, Sertraline and fluvoxamine or their officinal salt, and at least a pharmaceutically useful excipient.
4. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and fluoxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
5. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and citalopram or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
6. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and escitalopram or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
7. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and paroxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
8. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and Sertraline or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
9. the described pharmaceutical composition of claim 3, it comprises a kind of coupling of a kind of and fluvoxamine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
10. the described pharmaceutical composition of claim 1, it comprises the coupling of inhibitor of a kind of and 5-hydroxy tryptamine/norepinephrine reuptake of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
11. claim 1 or 10 described pharmaceutical compositions, it comprises the coupling of inhibitor of a kind of of saredutant or its officinal salt and a kind of 5-hydroxy tryptamine/norepinephrine reuptake that is selected from venlafaxine, duloxetine and midalcipran or their officinal salt, and at least a pharmaceutically useful excipient.
12. the described pharmaceutical composition of claim 11, it comprises a kind of coupling of a kind of and venlafaxine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
13. the described pharmaceutical composition of claim 11, it comprises a kind of coupling of a kind of and duloxetine or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
14. the described pharmaceutical composition of claim 11, it comprises a kind of coupling of a kind of and midalcipran or its officinal salt of saredutant or its officinal salt, and at least a pharmaceutically useful excipient.
15. the selective depressant of a kind of and serotonin reuptake transporter of saredutant or its officinal salt or with the coupling of the inhibitor of 5-hydroxy tryptamine/norepinephrine reuptake.
16. the coupling of the selective depressant of a kind of and a kind of serotonin reuptake transporter that is selected from fluoxetine, citalopram, escitalopram, paroxetine, Sertraline and fluvoxamine or their officinal salt of the described saredutant of claim 15 or its officinal salt.
17. the coupling of the inhibitor of a kind of and a kind of 5-hydroxy tryptamine/norepinephrine reuptake that is selected from venlafaxine, duloxetine and midalcipran or their officinal salt of the described saredutant of claim 15 or its officinal salt.
18. the described pharmaceutical composition of each of claim 1-14 is used to prepare the purposes of medicine, described medicine be used to prevent and treat the affective disorders that is selected from major depressive disorder, repellence depression, dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, cycloophrenia obstacle, non-specific bipolarity mental disorder, physical disease and causes, the affective disorders that brings out by material, the affective disorders of non-specific affective disorders; The anxiety neurosis of the anxiety neurosis that is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or brings out by material.
19. the described purposes of claim 18, it is used for prevention and treatment major depressive disorder.
20. the described purposes of claim 19, it is used for the treatment of the sexual dysfunction relevant with major depressive disorder.
21. the described pharmaceutical composition of claim 6 is used to prepare the purposes of medicine, described medicine is used for prevention and treatment is selected from major depressive disorder, repellence depression, dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, by the affective disorders that material brings out, the affective disorders of non-specific affective disorders; The anxiety neurosis of the anxiety neurosis that is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or brings out by material.
22. the described purposes of claim 21, it is used for prevention and treatment major depressive disorder.
23. the described purposes of claim 22, it is used for and the relevant sexual dysfunction of treatment major depressive disorder.
24. the described pharmaceutical composition of claim 7 is used to prepare the purposes of medicine, this medicine is used for prevention and treatment is selected from major depressive disorder, repellence depression, dysthymic disorder, non-specific depression, bipolar I type mental disorder, bipolar II type mental disorder, cycloophrenia obstacle, non-specific bipolarity mental disorder, the affective disorders that physical disease causes, by the affective disorders that material brings out, the affective disorders of non-specific affective disorders; The anxiety neurosis of the anxiety neurosis that is selected from stress state after panic attack, agoraphobia, social phobia, obsession, the wound, acute stress state, generalized anxiety disorder or brings out by material.
25. the described purposes of claim 24, it is used for the treatment of and prevents major depressive disorder.
26. the described purposes of claim 25, it is used for the treatment of the sexual dysfunction relevant with major depressive disorder.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR06/07050 | 2006-07-31 | ||
| FR0607050A FR2904221B1 (en) | 2006-07-31 | 2006-07-31 | PHARMACEUTICAL COMPOSITION CONTAINING IN ASSOCIATION SAREDUTANT AND FLUOXETINE. |
| FR07/00863 | 2007-02-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101495109A true CN101495109A (en) | 2009-07-29 |
Family
ID=37776830
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007800287391A Pending CN101495109A (en) | 2006-07-31 | 2007-07-30 | Pharmaceutical composition comprising, in combination, saredutant and a selective serotonin reuptake inhibitor or a serotonin/norepinephrine reuptake inhibitor |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN101495109A (en) |
| FR (1) | FR2904221B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666291A (en) * | 2013-11-26 | 2015-06-03 | 山东绿叶制药有限公司 | Application of O-desmethylvenlafaxine benzoate compound in preparation of medicines for improving sexual dysfunction |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2792835B3 (en) * | 1999-04-27 | 2001-05-25 | Sanofi Sa | USE OF SAREDUTANT FOR THE PREPARATION OF MEDICINES USEFUL IN THE TREATMENT OR PREVENTION OF ALL MOOD DISORDERS, ADAPTATION DISORDERS OR MIXED ANXIETY-DEPRESSION DISORDERS |
-
2006
- 2006-07-31 FR FR0607050A patent/FR2904221B1/en not_active Expired - Fee Related
-
2007
- 2007-07-30 CN CNA2007800287391A patent/CN101495109A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666291A (en) * | 2013-11-26 | 2015-06-03 | 山东绿叶制药有限公司 | Application of O-desmethylvenlafaxine benzoate compound in preparation of medicines for improving sexual dysfunction |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2904221B1 (en) | 2008-09-12 |
| FR2904221A1 (en) | 2008-02-01 |
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