# US 10,369,186 B2 · Method of treating decline in brain function comprising coadministration of citrulline and glutathione

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- Number: US 10,369,186 B2
- Document ID: US10369186B2
- Status: Granted
- Kind: B2
- Application number: 14/435,679
- Filed: 2013-10-30
- Published: 2015-09-24
- Granted: 2019-08-06
- Earliest claimed: 2012-10-30
- Assignees: Kyowa Hakko Bio Co., Ltd.
- Applicants: Kyowa Hakko Bio Co., Ltd.
- Inventors: Kota Kumagai; Masahiko Morita; Takahiro Hara; Kohji Fukunaga
- Web page: https://patentgrep.com/patent/US10369186B2

## CPC

- A61K 38/063: {Glutathione}
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/24: Antidepressants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

An objection of the present invention is to provide an agent for preventing or improving decline in brain function such as decreased perception ability, decreased memory learning ability, decreased thinking ability, decreased concentration, decreased attention, decreased judgment ability, depression, and decreased exercise performance caused thereby. According to the present invention, an agent for protecting brain neuronal cells, comprising citrulline or a salt thereof and glutathione or a salt thereof as active ingredients as well as an agent for preventing or improving decline in brain function, comprising citrulline or a salt thereof and glutathione or a salt thereof as active ingredients is provided.

## Claims

### Claim 1

A method of treating a decline in brain function in a subject comprising orally administering an effective amount of citrulline or a salt thereof and glutathione or a salt thereof to a subject in which the decline in brain function is caused by diminished cerebral blood flow, thereby treating the decline in brain function in the subject, and
wherein the decline in brain function is one or more selected from the group consisting of decreased perception ability, decreased memory learning ability, decreased thinking ability, decreased concentration, decreased attention, decreased judgment ability, and depression, and wherein the effective amount of citrulline or a salt thereof and glutathione or a salt thereof is 200 mg to 3 g of citrulline or a salt thereof and 200 mg to 3 g of glutathione or a salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method does not include surgery, therapy or diagnosis of the subject by a medical doctor.

### Claim 3 (depends on 1)

The method of claim 1, wherein the decline in brain function results in decreased exercise performance.

### Claim 4 (depends on 1)

The method of claim 1, wherein each of (a) citrulline or a salt thereof and (b) glutathione or a salt thereof is administered in an amount that, if administered alone, is not effective to treat a decline in brain function in the subject.

### Claim 5

A method of protecting brain neuronal cells in a subject with diminished cerebral blood flow comprising orally administering an effective amount of citrulline or a salt thereof and glutathione or a salt thereof to the subject, thereby protecting brain neuronal cells in the subject, wherein the effective amount of citrulline or a salt thereof and glutathione or a salt thereof is 200 mg to 3 g of citrulline or a salt thereof and 200 mg to 3 g of glutathione or a salt thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the method does not include surgery, therapy or diagnosis of the subject by a medical doctor.

### Claim 7 (depends on 5)

The method of claim 5, wherein each of (a) citrulline or a salt thereof and (b) glutathione or a salt thereof is administered in an amount that, if administered alone, is not effective to treat a decline in brain function in the subject.

### Claim 8 (depends on 7)

The method of claim 7, wherein the decline in brain function results in decreased exercise performance.