Composition and method for treatment of neuropsychiatric disorders
Inventors
Assignees
Publication Number
US-12311056-B2
Publication Date
2025-05-27
Expiration Date
2036-01-28
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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.
Core Innovation
The present invention discloses combination therapy compositions and methods that temporally modulate dysfunctional neural processes to reduce symptoms and/or signs of neuropsychiatric disorders, such as psychostimulant use disorder (PUD), post-traumatic stress disorder (PTSD), and levodopa-induced dyskinesia (LID), among others. The combination therapy involves two active ingredients: a dopamine (DA) agonist administered first to reactivate the stable, maladaptive neural circuit, followed by a 5-HT2, 5-HT3, or NK-1 receptor antagonist delivered at a suitable time to block reconsolidation of the reactivated neural circuit. This approach seeks to disrupt maladaptive neural plasticity underlying these disorders, resulting in progressive reduction of symptoms to subclinical levels.
Existing treatments for neuropsychiatric disorders like PUD, LID, and PTSD often provide inconsistent or limited efficacy, exhibit substantial side effects, or depend on complex dosing regimens that challenge patient adherence, especially in outpatient settings. The described invention addresses these limitations by delivering both active components as a single dosage form with programmed pharmacokinetic profiles, ensuring the intended temporal separation of peak drug effects and improving patient compliance.
The invention exemplifies its approach with immediate-release methylphenidate (as the DA agonist) and delayed, pulsatile-release ondansetron (as the 5-HT3 antagonist) in a single capsule, enabling a Tmax separation between 2 to 7 hours. This design achieves the required sequencing for efficacy and simplifies clinical use. The document provides additional formulation details and discusses other possible drug substance pairings to enable the same mechanism of action for various related neuropsychiatric and substance-use conditions.
Claims Coverage
The patent comprises three independent claims, each directed to methods of treating neuropsychiatric disorders using a specific single dosage form containing methylphenidate and ondansetron with defined release profiles.
Single dosage form containing immediate-release methylphenidate and delayed, pulsatile-release ondansetron for psychostimulant use disorder
A method of treating psychostimulant use disorder by: - Identifying a patient meeting DSM-5 criteria for psychostimulant use disorder. - Administering a single dosage form comprising: - Immediate-release methylphenidate or pharmaceutically acceptable salt with an in vitro dissolution rate of ≥90% in ≤2 hours or ≥80% in ≤1 hour under simulated gastric or intestinal conditions, reaching Cmax at Tmax1. - Delayed and pulsatile-release ondansetron or pharmaceutically acceptable salt with an in vitro dissolution of ≤10% in ≥3 hours and ≥80% in ≤7 hours under same conditions, reaching Cmax at Tmax2. - The difference between Tmax1 and Tmax2 is about 2 to about 7 hours.
Single dosage form containing immediate-release methylphenidate and delayed, pulsatile-release ondansetron for tobacco use disorder
A method of treating tobacco use disorder by: - Identifying a patient meeting DSM-5 criteria for tobacco use disorder. - Administering a single dosage form comprising: - Immediate-release methylphenidate or pharmaceutically acceptable salt with the above specified in vitro dissolution and Tmax1. - Delayed and pulsatile-release ondansetron or pharmaceutically acceptable salt with the above specified in vitro dissolution and Tmax2. - The difference between Tmax1 and Tmax2 is about 2 to about 7 hours.
Single dosage form containing immediate-release methylphenidate and delayed, pulsatile-release ondansetron for alcohol use disorder
A method of treating alcohol use disorder by: - Identifying a patient meeting DSM-5 criteria for alcohol use disorder. - Administering a single dosage form comprising: - Immediate-release methylphenidate or pharmaceutically acceptable salt with an in vitro dissolution rate-profile as above and Tmax1. - Delayed, pulsatile-release ondansetron or pharmaceutically acceptable salt with in vitro dissolution as above and Tmax2. - The difference between Tmax1 and Tmax2 is about 2 to about 7 hours.
The inventive features center on timed-sequence delivery of immediate-release methylphenidate and delayed-release ondansetron in a single dosage form for the treatment of psychostimulant, tobacco, and alcohol use disorders.
Stated Advantages
The invention provides a convenient and optimized single dosage form that simplifies administration and promotes patient compliance, especially in populations where adherence is historically low.
By temporally modulating dysfunctional neural processes, the therapy enables progressive reduction of neuropsychiatric disorder symptoms to subclinical levels, including conditions refractory to previous pharmacological therapies.
The design ensures the intended sequence of drug action in vivo, overcoming the prior limitation of strict administration timing, thus facilitating effective outpatient treatment.
Documented Applications
Treatment of psychostimulant use disorder, including misuse of cocaine, methamphetamine, and related drugs.
Treatment of tobacco use disorder.
Treatment of alcohol use disorder.
Treatment of other substance-related disorders (including cannabis use disorder).
Treatment of post-traumatic stress disorder (PTSD) and other trauma- and stressor-related disorders.
Treatment of levodopa-induced dyskinesia (LID) and other dyskinesias.
Treatment of behavioral addictive disorders such as compulsive gambling and internet addiction.
Treatment of anxiety disorders, obsessive-compulsive disorders, and feeding/eating disorders as stated in the description.
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