Medicinal agent and beverage/food for preventing cerebral dysfunction and improving same

Abstract

Disclosed is a means for improving the symptoms of a cerebral dysfunction. The present inventors made a new discovery that the activity of brain aromatic monoamines increases when sepiapterin is administered peripherally. Disclosed, therefore, is a medicinal agent, which contains at least sepiapterin or a salt thereof, for preventing or improving cerebral dysfunction. Also disclosed is a beverage/food, which contains at least sepiapterin or a salt thereof, for preventing or improving cerebral dysfunction. Unlike tetrahydrobiopterin and the like, sepiapterin can control reductions in the brain neuron levels of brain aromatic monoamines (serotonin, dopamine, noradrenaline, and the like) and increase the activity thereof even when administered peripherally. Therefore, sepiapterin may be effective for cerebral dysfunctions, which are due to reductions in the brain neuron levels of brain aromatic monoamines, such as depression, bulimia, autism, impaired consciousness and concentration, cognitive disorders and other central mental disorders, as well as myotonia, rigidity, tremors, and other central motor disorders.

Claims

1. A method of preventing or improving cerebral dysfunction in a subject with a central motor disorder, the method comprising peripherally administering a composition which contains at least sepiapterin to the subject with cerebral dysfunction, wherein the central motor disorder is myotonia, and wherein the composition is administered in an amount sufficient to suppress a decrease in aromatic monoamines in the brain.

2. The method of claim 1, wherein the composition is a food or drink which contains sepiapterin as an active ingredient.

3. The method of claim 1, wherein the composition is administered at a dose of 0.1 to 100 mg/kg of sepiapterin.

4. The method of claim 1, wherein the aromatic monoamines comprise serotonin, dopamine, adrenaline, and/or noradrenaline.

5. The method of claim 1, wherein the composition is a food or drink which contains sepiapterin as an active ingredient.

6. The method of claim 1, wherein the composition is administered at a dose of 0.1 to 100 mg/kg of sepiapterin.

7. The method of claim 1, wherein the composition further comprises a pharmacologically acceptable carrier.

8. The method of claim 1, wherein the composition further comprises a pharmacologically acceptable carrier.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is an illustration which depicts a metabolic system of aromatic monoamine in neurons in a brain.

(2) FIG. 2A is a graph which shows change in the total amount of biopterin taken up into PC12 cells with the lapse of time in Example 1.

(3) FIG. 2B is a graph which shows change in the total amount of biopterin taken up into RBL2H3 cells with the lapse of time in Example 1.

(4) FIG. 3 is a graph which shows an amount of downward migration of each of tetrahydrobiopterin (BH4), sepiapterin (SP) and 5-hydroxytryptophan (5HTP) added over the upper side of the cell sheet of the brain blood vessel wall model (RBT24H) in Example 2.

(5) FIG. 4A is a graph which shows amounts of sepiapterin (SP), dihydrobiopterin (BH2) and tetrahydrobiopterin (BH4) accumulated in CTX, TNA2 cells on addition of sepiapterin (SP) in Example 3.

(6) FIG. 4B is a graph which shows amounts of dihydrobiopterin (BH2) and tetrahydrobiopterin (BH4) accumulated in the CTX INA 2 cells on addition of tetrahydrobiopterin (BH4) in Example 3.

(7) FIG. 5A is a graph which shows change in the amount of tetrahydrobiopterin in the brain with the lapse of time after administration of sepiapterin in an experiment with rats in Example 4.

(8) FIG. 5B is a graph which shows change in the amount of serotonin in the brain with the lapse of time after administration of sepiapterin in the experiment with rats in Example 4.

(9) FIG. 5C is a graph which shows change in the amount of 5-hydroxyindoleacetic acid in the brain after administration of sepiapterin in the experiment with rats in Example 4.

(10) FIG. 6 is a graph which shows the amount of serotonin in the brain after administration of sepiapterin in an experiment with mice (hph-1) in Example 5.

(11) FIG. 7 is a graph which shows “immobile” time after administration of sepiapterin in a forced swim test with mice (NZB) in Example 6.