Composition and method for treatment of neuropsychiatric disorders

Abstract

The present invention relates to a composition and method for combinative therapy, capable of temporarily regulating inherent dysfunctional neural processes and reducing symptoms and/or signs of neuropsychiatric disorders including, but not limited to, psychostimulant use disorder (PUD) and other substance-related additive disorders, post-traumatic stress disorder (PTSD) and other trauma- and stress-related disorders, and levodopa-induced dyskinesia (LID) and other types of dyskinesias. The present specification shows specific examples of a dosage form.

What is claimed is: 
     
         1 . A combination therapy composition for treatment of neuropsychiatric disorders, comprising component 1 as an agonist for reactivating a dysfunctional neural circuit and component 2 as an antagonist for blocking reconsolidation of a reactivated dysfunctional neural circuit. 
     
     
         2 . The combination therapy composition of  claim 1 , wherein the neuropsychiatric disorders are selected from the group consisting of psychostimulant use disorder (PUD) and other substance-related and addictive disorders, post-traumatic stress disorder (PTSD) and other trauma- and stressor-related disorders, and levodopa-induced dyskinesia (LID) and other types of dyskinesia. 
     
     
         3 . The combination therapy composition of  claim 2 , wherein the neuropsychiatric disorders are selected from the group consisting of other substance-related disorders, including, but not limited to, tobacco use disorder, alcohol use disorder and  cannabis  use disorder; behavioral addictive disorders, including, but not limited to, habitual gambling and internet addictions; other trauma and stressor-related disorders, including, but not limited to, reactive attachment disorder, acute stress disorder and adjustment disorder; anxiety disorders, including generalized anxiety disorder, panic disorder, agoraphobia, and substance/drug-induced anxiety disorders; obsessive-compulsive disorders, including, but not limited to, body dysmorphic disorder, hoarding disorder, trichotillomania, and excoriation disorder; and feeding and eating disorders, including but not limited to anorexia nervosa, bulimia nervosa, and binge-eating disorder. 
     
     
         4 . The combination therapy composition of  claim 1 , wherein component 1 is selected from the group consisting of small molecules, other types of molecules, and modifications thereof (for example, formulations, prodrugs, etc.). 
     
     
         5 . The combination therapy composition of  claim 4 , wherein the other types of molecules are selected from the group consisting of small interfering ribonucleic acids (siRNAs), micro-RNAs, antisense oligonucleotides, aptamers, peptides, proteins, naturally occurring organic or inorganic molecules, chemical elements, and any synthetic compounds greater or smaller than small molecules. 
     
     
         6 . The combination therapy composition of  claim 1 , wherein component 1 is a pharmacologically effective indirect or direct DA agonist or a pharmaceutically acceptable salt thereof, which exhibits or does not exhibits norepinephrine (NE) and/or serotonin (5-HT) agonistic efficacy. 
     
     
         7 . The combination therapy composition of  claim 1 , wherein component 1 has an immediate-release profile, delayed-release profile, pulsatile-release profile, or extended/prolonged-release profile. 
     
     
         8 . The combination therapy composition of  claim 1 , wherein component 1 has a release profile corresponding to a dissolution rate of 90% or more within 2 hours under simulated gastric or intestinal dissolution conditions. 
     
     
         9 . The combination therapy composition of  claim 1 , wherein component 1 has a terminal elimination half-life of 20 hours or less in a human body. 
     
     
         10 . The combination therapy composition of  claim 1 , wherein component 2 is selected from the group consisting of small molecules, other types of molecules, and modifications thereof (for example, formulations, prodrugs, etc.) 
     
     
         11 . The combination therapy composition of  claim 10 , wherein the other types of molecules are selected from the group consisting of small interfering ribonucleic acids (siRNAs), micro-RNAs, antisense oligonucleotides, aptamers, peptides, proteins, naturally occurring organic or inorganic molecules, chemical elements, and any synthetic compounds greater or smaller than small molecules. 
     
     
         12 . The combination therapy composition of  claim 1 , wherein component 2 is selected from the group consisting of selective or non-selective receptor antagonists or inverse-agonists of 5-HT2 receptor, selective or non-selective receptor antagonists or inverse-agonists of 5-HT3 receptor, and selective or non-selective receptor antagonists or inverse-agonists of NK-1 receptor, including 5-HT2, 5-HT3 and NK-1 receptor subtypes, single nucleotide polymorphisms and other transcriptional, translational and post-transcriptional modifications of each receptor expressed in humans. 
     
     
         13 . The combination therapy composition of  claim 1 , wherein component 2 has an immediate-release profile, delayed-release profile, pulsatile-release profile, or extended/prolonged-release profile. 
     
     
         14 . The combination therapy composition of  claim 1 , wherein component 2 has a release profile corresponding to a dissolution rate ranging from 10% or less at 3 hours and more to 80% or more at 7 hours or less under simulated gastric or intestinal dissolution conditions. 
     
     
         15 . The combination therapy composition of  claim 1 , wherein component 2 has a terminal elimination half-life of 20 hours or less in a human body. 
     
     
         16 . The combination therapy composition of  claim 1 , wherein component 1 has an immediate- or pulsatile-release profile, and component 2 has a delayed- or pulsatile-release profile. 
     
     
         17 . The combination therapy composition of  claim 1 , wherein Tmax separation between the plasma or serum concentration of a pharmacologically active form of component 1 and the plasma or serum concentration of a plasma or serum concentration of a physiologically active form of component 2 in humans ranges from 1 hour to 12 hours. 
     
     
         18 . The combination therapy composition of  claim 1 , wherein the composition is in a dosage form selected from among tablets, capsules, gels, suspensions, films, patches and suppositories. 
     
     
         19 . The combination therapy composition of  claim 1 , wherein component 1 is methylphenidate or any immediate-release formulation of methylphenidate, and component 2 is component 2 is any delayed, pulsatile-release formulation of ondansetron. 
     
     
         20 . The combination therapy composition of  claim 19 , wherein a dose of methylphenidate is equivalent to 0.1 to 80 mg of methylphenidate hydrochloride, and a dose of dose of ondansetron in the dosage form is equivalent to 0.1 to 32 mg of ondansetron hydrochloride. 
     
     
         21 . A combination therapy method for treatment of a neuropsychiatric disorder, comprising a step of administering, to a subject suffering from the neuropsychiatric disorder, component 1 as an agonist for reactivating a dysfunctional neural circuit and component 2 as an antagonist for blocking reconsolidation of a reactivated dysfunctional neural circuit, wherein an effective amount of component 1 is first administered and an effective amount of ingredient is administered later, in such a manner that a time interval between the administration of component 1 and the administration of component 2 is such that Tmax separation between a plasma or serum concentration of a pharmacologically active form of component 1 and a plasma or serum concentration of a plasma or serum concentration of a physiologically active form of component 2 in humans ranges from 1 hour to 12 hours. 
     
     
         22 . The combination therapy method of  claim 21 , wherein the neuropsychiatric disorder is selected from the group consisting of psychostimulant use disorder (PUD) and other substance-related and addictive disorders, post-traumatic stress disorder (PTSD) and other trauma- and stressor-related disorders, and levodopa-induced dyskinesia (LID) and other types of dyskinesia. 
     
     
         23 . The combination therapy method of  claim 22 , wherein the neuropsychiatric disorder is selected from the group consisting of other substance-related disorders, including, but not limited to, tobacco use disorder, alcohol use disorder and  cannabis  use disorder; behavioral addictive disorders, including, but not limited to, habitual gambling and internet addictions; other trauma and stressor-related disorders, including, but not limited to, reactive attachment disorder, acute stress disorder and adjustment disorder; anxiety disorders, including generalized anxiety disorder, panic disorder, agoraphobia, and substance/drug-induced anxiety disorders; obsessive-compulsive disorders, including, but not limited to, body dysmorphic disorder, hoarding disorder, trichotillomania, and excoriation disorder; and feeding and eating disorders, including but not limited to anorexia nervosa, bulimia nervosa, and binge-eating disorder 
     
     
         24 . The combination therapy method of  claim 21 , wherein component 1 has an immediate- or pulsatile-release profile, and component 2 has a delayed- or pulsatile-release profile. 
     
     
         25 . The combination therapy method of  claim 21 , wherein component 1 is methylphenidate or any immediate-release formulation of methylphenidate, and component 2 is component 2 is any delayed, pulsatile-release formulation of ondansetron. 
     
     
         26 . The combination therapy method of  claim 25 , wherein a dose of methylphenidate is equivalent to 0.1 to 80 mg of methylphenidate hydrochloride, and a dose of dose of ondansetron in the dosage form is equivalent to 0.1 to 32 mg of ondansetron hydrochloride.