Therapeutic drug for motor complications in parkinson's disease

Abstract

The present disclosure provides a therapeutic drug that is useful for the treatment of motor fluctuations (e.g., wearing-off) in Parkinson's disease. In particular, the present disclosure provides a composition and method for treating, improving, suppressing the progression, or preventing motor complications in Parkinson's disease, especially motor fluctuation, comprising tandospirone or a pharmaceutically acceptable salt thereof, wherein the tandospirone or a pharmaceutically acceptable salt thereof is parenterally administered.

1 .- 29 . (canceled) 
     
     
         30 . A method of treating, improving, or preventing motor fluctuations, comprising transdermally administering an effective amount of tandospirone or a pharmaceutically acceptable salt thereof to a subject in need thereof, wherein treatment, improvement, or prevention of motor fluctuations comprises at least one selected from the group consisting of prolongation of an antiparkinsonian action effective time (ON-time), a reduction of an antiparkinsonian action non-response time (OFF-time), and a combination thereof. 
     
     
         31 . The method of  claim 30 , wherein the subject is undergoing drug therapy for Parkinson's disease. 
     
     
         32 . The method of  claim 30 , wherein the subject is undergoing drug therapy selected from the group consisting of drug therapy for Parkinson's disease using a levodopa containing formulation, a levodopa metabolite inhibitor, or a dopamine receptor agonist and therapy using an adjunct agent for Parkinson's disease. 
     
     
         33 . The method of  claim 30 , wherein the subject is undergoing dopamine replacement therapy for Parkinson's disease. 
     
     
         34 . The method of  claim 30 , wherein the subject is undergoing levodopa therapy for Parkinson's disease. 
     
     
         35 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises reduction of an antiparkinsonian action non-response time (OFF-time). 
     
     
         36 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises prolongation of an antiparkinsonian action effective time (ON-time). 
     
     
         37 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises reducing an antiparkinsonian action non-response time (OFF-time) and prolonging an antiparkinsonian action effective time (ON-time) without troublesome dyskinesia. 
     
     
         38 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises at least one selected from sustained maintenance of a dopamine level in a striatal synaptic cleft, suppression of a rapid change in a dopamine level, and suppression of intermittent dopamine receptor stimulation in a subject. 
     
     
         39 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises reducing an antiparkinsonian action non-response time (OFF-time) and prolonging an antiparkinsonian action effective time (ON-time) without exacerbating a levodopa induced dyskinesia (PD-LID) symptom in Parkinson's disease. 
     
     
         40 . The method of  claim 30 , comprising reducing an antiparkinsonian action non-response time (OFF-time) and prolonging an antiparkinsonian action effective time (ON-time) without a rebound symptom of levodopa induced dyskinesia (PD-LID). 
     
     
         41 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises reducing an antiparkinsonian action non-response time (OFF-time) and prolonging an antiparkinsonian action effective time (ON-time) without a dyskinesia symptom. 
     
     
         42 . The method of  claim 30 , wherein the treatment, improvement, or prevention comprises prolonging an antiparkinsonian action effective time (ON-time) without dyskinesia. 
     
     
         43 . The method of  claim 30 , wherein the administration is accomplished with a transdermally administered formulation. 
     
     
         44 . The method of  claim 30 , wherein a drug dosage of the tandospirone or a pharmaceutically acceptable salt thereof is 0.1 to 500 mg per day as a free form of tandospirone. 
     
     
         45 . The method of  claim 30 , wherein a drug dosage of the tandospirone or a pharmaceutically acceptable salt thereof is 3 to 250 mg per day as a free form of tandospirone. 
     
     
         46 . The method of  claim 30 , wherein an amount of drug penetration for the tandospirone or a pharmaceutically acceptable salt thereof is 0.1 to 100 mg per day as a free form of tandospirone. 
     
     
         47 . The method of  claim 30 , wherein an amount of drug penetration for the tandospirone or a pharmaceutically acceptable salt thereof is 1 to 60 mg per day as a free form of tandospirone. 
     
     
         48 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is provided as a transdermally administered formulation, and a total applied area per dose is 1 to 100 cm 2 . 
     
     
         49 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is provided as a transdermally administered formulation, and a total applied area per dose is 9 to 60 cm 2 . 
     
     
         50 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is administered so that a human blood (plasma) tandospirone concentration is 0.1 to 15 ng/mL for 12 hours or longer per day; and/or 0.1 to 15 ng/mL for 8 to 16 hours after administration of the tandospirone or a pharmaceutically acceptable salt thereof. 
     
     
         51 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is administered so that an amount of change in striatal [ 11 C] raclopride receptor binding from before levodopa administration to 1 hour after administration (amount of change B/1 h) after administering the tandospirone or a pharmaceutically acceptable salt thereof is less than 10%. 
     
     
         52 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is provided as an adjunct of levodopa. 
     
     
         53 . The method of  claim 30 , wherein the tandospirone or a pharmaceutically acceptable salt thereof is administered so that a maximum blood concentration of human blood (plasma) tandospirone in a steady state is 1 to 15 ng/mL, and a ratio of a minimum concentration, with respect to the maximum concentration of human blood (plasma) tandospirone concentration as 100%, is 30 to 95% after administration of the tandospirone or a pharmaceutically acceptable salt thereof. 
     
     
         54 . The method of  claim 30 , wherein the treatment, improvement, or prevention consists of reducing an antiparkinsonian action non-response time (OFF-time) and/or prolonging an antiparkinsonian action effective time (ON-time). 
     
     
         55 . A method of prolongation of an antiparkinsonian action effective time (ON-time) or a reduction of an antiparkinsonian action non-response time (OFF-time) in a patient with Parkinson's disease (PD), wherein the patient is being treated with levodopa, wherein the method comprises transdermally administering an effective amount of tandospirone or a pharmaceutically acceptable salt thereof to a subject in need thereof.