US2016113942A1PendingUtilityA1

Compositions comprising a prostaglandin for treating neuropsychiatric conditions

33
Individually held — no corporate assignee on recordPriority: Jan 24, 2011Filed: Jan 6, 2016Published: Apr 28, 2016
Est. expiryJan 24, 2031(~4.5 yrs left)· nominal 20-yr term from priority
Inventors:Fabrizio Mastronardi
A61P 9/10A61P 43/00A61P 25/30A61P 25/24A61P 25/28A61P 25/14A61P 25/22A61P 25/16A61P 29/00A61P 25/18A61P 25/20A61P 25/08A61P 25/02A61K 31/53A61K 45/06A61K 31/216A61P 25/00A61K 31/4196A61K 31/165A61K 31/16A61K 31/4706A61K 31/5575A61P 21/02A61K 31/4412C07C 405/00
33
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The present invention relates to methods and compositions for the treatment of neuropsychiatric conditions (e.g., bipolar disorder) by administration of prostaglandin or prostaglandin derivatives (e.g., latanoprost) to a subject (e.g., a human).

Claims

exact text as granted — not AI-modified
1 - 49 . (canceled) 
     
     
         50 . A method of treating a subject having a neuropsychiatric condition, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof. 
     
     
         51 . The method of  claim 50 , wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, is administered in an amount sufficient to inhibit glycogen synthase kinase-3 (GSK-3) in the subject. 
     
     
         52 . The method of  claim 51 , wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, is administered in an amount sufficient to produce a steady state plasma concentration of prostaglandin, or derivative thereof, of from about 1 pg/ml to about 10 ng/ml. 
     
     
         53 . The method of  claim 50 , wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, is deuterium-enriched and/or nitrosylated. 
     
     
         54 . The method of  claim 50 , wherein the prostaglandin, or derivative thereof, is selected from the group consisting of propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-hept-5-enoate (latanoprost), propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]-hept-5-enoate (travoprost), 7-[(IR,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxo-cyclopentyl]-heptanoic acid (PGE1), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxo-cyclopentyl]-hept-5-enoic acid (PGE2), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dienyl]-5-oxocyclopentyl]-hept-5-enoic acid (PGE3), (Z)-7-[(1R,2R,5S)-5-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxocyclopentyl]-hept-5-enoic acid (PGD2), 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E)-(3S)-3-hydroxy-l-octenyl]-cyclopentyl]-heptanoic acid (PGF1α), (Z)-7-[(IR,2R,3R,5S)-3,5-dihydroxy-2-[(E)-(3S)-3-hydroxy-l-octenyl]-cyclopentyl]-5-heptenoic acid (PGF2α), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dienyl]cyclopentyl]-hept-5-enoic acid (PGF3α), (5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]-pentanoic acid (PGI2/prostacyclin), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]-hept-5-enoic acid (unoprostone), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethyl-hept-5-enamide (bimatoprost), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]-hept-5-enoic acid (fluprostenol), (Z)-7-[(1R,3R)-2-[(E,3R)-3-hydroxy-4,4-dimethyloct-1-enyl]-3-methyl-5-oxocyclopentyl]-hept-5-enoic acid (trimoprostil), (2R,3R,4R)-4-hydroxy-2-(7-hydroxyheptyl)-3-[(E)-4-hydroxy-4-methyloct-1-enyl]-cyclopentan-1-one (rioprostil), (Z)-7-[(1R,3R,5S)-2-[(E,3R)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]-hept-5-enoic acid (cloprostenol), (Z)-7-[(1S,2R,3R,5S)-2-[(2S)-3-(3-chlorophenoxy)-2-hydroxypropyl]sulfanyl-3,5-dihydroxycyclopentyl]-hept-5-enoic acid (luprostiol), (Z)-7-[(2R)-3,5-dihydroxy-2-[(E)-2-[2-(phenoxymethyl)-1,3-dioxolan-2-yl]ethenyl]cyclopentyl]-hept-5-enoic acid (etiproston), (E)-7-[3,5-dihydroxy-2-[(E)-3-hydroxy-4-thiophen-3-yloxybut-1-enyl]cyclopentyl]-hept-5-enoic acid (tiaprost), propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]-hept-5-enoate (isopropyl unoprostone), methyl-7-[(1R,2R,3R)-3-hydroxy-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopentyl]-heptanoate (misoprostol), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-(phenoxy)but-1-enyl]-5-oxocyclopentyl]-N-methylsulfonylhept-5-enamide (sulprostone), methyl (E)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-4,4-dimethyloct-1-enyl]-5-oxocyclopentyl]hept-2-enoate (gemeprost), methyl (Z)-7-[(1R,3R,5S)-2-[(3S)-5-cyclohexyl-3-hydroxypent-1-ynyl]-3,5-dihydroxycyclopentyl]hept-5-enoate (alfaprostol), and methyl (2Z,5Z)-7-[(2R)-2-[(E,3R)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]hepta-2,5-dienoate (delprostenate), and pharmaceutically acceptable salts thereof. 
     
     
         55 . The method of  claim 54 , wherein the prostaglandin, or derivative thereof, is propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-hept-5-enoate (latanoprost). 
     
     
         56 . The method of  claim 55 , wherein the latanoprost is present in the pharmaceutical composition at a concentration of from about 0.00001% to about 0.2% (w/v). 
     
     
         57 . The method of  claim 54 , wherein the prostaglandin, or derivative thereof, is propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]-hept-5-enoate (travoprost). 
     
     
         58 . The method of  claim 57 , wherein the travoprost is present in the pharmaceutical composition at a concentration of from about 0.00001% to about 0.2% (w/v). 
     
     
         59 . The method of  claim 54 , wherein the prostaglandin, or derivative thereof, is (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethyl-hept-5-enamide (bimatoprost). 
     
     
         60 . The method of  claim 59 , wherein the bimatoprost is present in the pharmaceutical composition at a concentration of from about 0.00001% to about 0.2% (w/v). 
     
     
         61 . The method of  claim 50 , further comprising administering an additional therapeutic agent, wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, and the additional therapeutic agent are each administered in an amount that together is effective for the treatment of the neuropsychiatric condition. 
     
     
         62 . The method of  claim 61 , wherein the additional therapeutic agent is selected from the group consisting of an anxiolytic, antipsychotic, antidepressant, neuroleptic, tranquilizer, melatonin agonist, melatonin antagonist, melatonergic agent, benzodiazepine, barbiturate, 5-hydroxtryptamine (5-HT) antagonist, monoamine oxidase inhibitor, lithium, valproic acid, sodium valproate, lamotrigine, carbamazepine, gabapentin, topiramate, selective serotonin reuptake inhibitor (SSRI), specific monoamine reuptake inhibitor, anticholinergic, catechol-O-methyl transferase (COMT) inhibitor, monoamine oxidase-B (MOA-B) inhibitor, antioxidant, A 2A  adenosine receptor antagonist, cholinergic agonist, serotonin receptor antagonist, dopamine receptor agonist, antiepileptic, anti-Alzheimer's agent, beta-secretase (BACE) inhibitor, gamma-secretase inhibitor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, nonsteroidal anti-inflammatory drug (NSAID), and 5-HT1A receptor agonist or partial agonist. 
     
     
         63 . The method of  claim 50 , wherein the neuropsychiatric condition is a psychotic disorder, cognitive disorder, anxiety disorder, or attention disorder. 
     
     
         64 . The method of  claim 63 , wherein the psychotic disorder is selected from the group consisting of bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, drug-induced psychotic disorder, depression, sundowners syndrome due to Alzheimer's disease or other dementia, and post-traumatic stress disorder. 
     
     
         65 . The method of  claim 64 , wherein the psychotic disorder is bipolar disorder. 
     
     
         66 . The method of  claim 63 , wherein the cognitive disorder is selected from the group consisting of amnestic disorder, age-related cognitive decline, and dementia associated with a neuroinflammatory condition. 
     
     
         67 . The method of  claim 63 , wherein the anxiety disorder is selected from the group consisting of a generalized anxiety disorder, obsessive compulsive disorder, social phobia, panic attack, premenstrual syndrome, and premenstrual dysphoric disorder. 
     
     
         68 . The method of  claim 63 , wherein the attention disorder is selected from the group consisting of attention deficit hyperactivity disorder, Tourette's syndrome, eating disorder, and autism. 
     
     
         69 . The method of  claim 50 , wherein the subject is a human. 
     
     
         70 . The method of  claim 50 , wherein the pharmaceutical composition is administered intramuscularly, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, topically, locally, by inhalation, injection, infusion, continuous infusion, localized perfusion bathing target cells directly, catheter, lavage, in cremes, or lipid compositions. 
     
     
         71 . The method of  claim 50 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier. 
     
     
         72 . A composition comprising a therapeutically effective amount of a prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, and an additional therapeutic agent. 
     
     
         73 . The composition of  claim 72 , wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, or the additional therapeutic agent inhibits GSK-3. 
     
     
         74 . The composition of  claim 72 , wherein the prostaglandin, derivative thereof, or pharmaceutically acceptable sat thereof, is deuterium-enriched and/or nitrosylated. 
     
     
         75 . The composition of  claim 72 , wherein the prostaglandin, or derivative thereof, is selected from the group consisting of propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-hept-5-enoate (latanoprost), propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]-hept-5-enoate (travoprost), 7-[(IR,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxo-cyclopentyl]-heptanoic acid (PGE1), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-5-oxo-cyclopentyl]-hept-5-enoic acid (PGE2), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dienyl]-5-oxocyclopentyl]-hept-5-enoic acid (PGE3), (Z)-7-[(1R,2R,5S)-5-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxocyclopentyl]-hept-5-enoic acid (PGD2), 7-[(IR,2R,3R,5S)-3,5-dihydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-cyclopentyl]-heptanoic acid (PGF1α), (Z)-7-[(IR,2R,3R,5S)-3,5-dihydroxy-2-[(E)-(3S)-3-hydroxy-1-octenyl]-cyclopentyl]-5-heptenoic acid (PGF2α), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S,5Z)-3-hydroxyocta-1,5-dienyl]cyclopentyl]-hept-5-enoic acid (PGF3α), (5Z)-5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-ylidene]-pentanoic acid (PGI2/prostacyclin), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]-hept-5-enoic acid (unoprostone), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethyl-hept-5-enamide (bimatoprost), (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]-hept-5-enoic acid (fluprostenol), (Z)-7-[(1R,3R)-2-[(E,3R)-3-hydroxy-4,4-dimethyloct-1-enyl]-3-methyl-5-oxocyclopentyl]-hept-5-enoic acid (trimoprostil), (2R,3R,4R)-4-hydroxy-2-(7-hydroxyheptyl)-3-[(E)-4-hydroxy-4-methyloct-1-enyl]-cyclopentan-1-one (rioprostil), (Z)-7-[(1R,3R,5S)-2-[(E,3R)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]-hept-5-enoic acid (cloprostenol), (Z)-7-[(1S,2R,3R,5S)-2-[(2S)-3-(3-chlorophenoxy)-2-hydroxypropyl]sulfanyl-3,5-dihydroxycyclopentyl]-hept-5-enoic acid (luprostiol), (Z)-7-[(2R)-3,5-dihydroxy-2-[(E)-2-[2-(phenoxymethyl)-1,3-dioxolan-2-yl]ethenyl]cyclopentyl]-hept-5-enoic acid (etiproston), (E)-7-[3,5-dihydroxy-2-[(E)-3-hydroxy-4-thiophen-3-yloxybut-1-enyl]cyclopentyl]-hept-5-enoic acid (tiaprost), propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(3-oxodecyl)cyclopentyl]-hept-5-enoate (isopropyl unoprostone), methyl-7-[(1R,2R,3R)-3-hydroxy-2-[(E)-4-hydroxy-4-methyloct-1-enyl]-5-oxocyclopentyl]-heptanoate (misoprostol), (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3R)-3-hydroxy-4-(phenoxy)but-1-enyl]-5-oxocyclopentyl]-N-methylsulfonylhept-5-enamide (sulprostone), methyl (E)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-4,4-dimethyloct-1-enyl]-5-oxocyclopentyl]-hept-2-enoate (gemeprost), methyl (Z)-7-[(1R,3R,5S)-2-[(3S)-5-cyclohexyl-3-hydroxypent-1-ynyl]-3,5-dihydroxycyclopentyl]-hept-5-enoate (alfaprostol), and methyl (2Z,5Z)-7-[(2R)-2-[(E,3R)-4-(3-chlorophenoxy)-3-hydroxybut-1-enyl]-3,5-dihydroxycyclopentyl]-hepta-2,5-dienoate (delprostenate), and pharmaceutically acceptable salts thereof. 
     
     
         76 . The composition of  claim 75 , wherein the prostaglandin, or derivative thereof, is propan-2-yl-(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-hept-5-enoate (latanoprost). 
     
     
         77 . The composition of  claim 76 , wherein the latanoprost is present at a concentration of from about 0.00001% to about 0.2% (w/v). 
     
     
         78 . The composition of  claim 72 , wherein the additional therapeutic agent is selected from the group consisting of an anxiolytic, antipsychotic, antidepressant, neuroleptic, tranquilizer, melatonin agonist, melatonin antagonist, melatonergic agent, benzodiazepine, barbiturate, 5-hydroxtryptamine (5-HT) antagonist, monoamine oxidase inhibitor, lithium, valproic acid, sodium valproate, lamotrigine, carbamazepine, gabapentin, topiramate, selective serotonin reuptake inhibitor (SSRI), specific monoamine reuptake inhibitor, anticholinergic, catechol-O-methyl transferase (COMT) inhibitor, monoamine oxidase-B (MOA-B) inhibitor, antioxidant, A 2A  adenosine receptor antagonist, cholinergic agonist, serotonin receptor antagonist, dopamine receptor agonist, antiepileptic, anti-Alzheimer's agent, beta-secretase (BACE) inhibitor, gamma-secretase inhibitor, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, nonsteroidal anti-inflammatory drug (NSAID), and 5-HT1A receptor agonist or partial agonist. 
     
     
         79 . The composition of  claim 78 , wherein the composition is administered to a subject intramuscularly, intravenously, intradermally, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctival, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularally, orally, topically, locally, by inhalation, injection, infusion, continuous infusion, localized perfusion bathing target cells directly, catheter, lavage, in cremes, or lipid compositions. 
     
     
         80 . A kit comprising packaging and a pharmaceutical composition comprising a prostaglandin, derivative thereof, or pharmaceutically acceptable salt thereof, that inhibits GSK-3, wherein the packaging is labeled to indicate that the pharmaceutical composition is useful to treat a neuropsychiatric condition.

Join the waitlist — get patent alerts

Track US2016113942A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.