# US 10,500,181 B2 · Methods and compositions for treatment for coronary and arterial aneurysmal subarachnoid hemorrhage

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- Number: US 10,500,181 B2
- Document ID: US10500181B2
- Status: Granted
- Kind: B2
- Application number: 15/955,370
- Filed: 2018-04-17
- Published: 2018-12-20
- Granted: 2019-12-10
- Earliest claimed: 2008-01-31
- Assignees: Vanderbilt University
- Applicants: Vanderbilt University
- Inventors: Marshall L. Summar; Frederick E. Barr; Reid Carleton Thompson
- Web page: https://patentgrep.com/patent/US10500181B2

## CPC

- 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 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/08: Vasodilators for multiple indications
- 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 33/00: Antiparasitic agents
- 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

Methods and compositions for treating a complication associated with aneurysmal subarachnoid hemorrhage (SAH), the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof. Methods and compositions for treating vasospasm, the method comprising administering an effective amount of a nitric oxide precursor to a subject in need thereof.

## Claims

### Claim 1

A method of treating a complication associated with aneurysmal subarachnoid hemorrhage (SAH) in a subject having SAH and relative hypocitrullinemia, wherein the complication is cerebral vasospasm, said method comprising intravenously administering to the subject suffering from SAH and relative hypocitrullinemia an effective amount of citrulline, a pharmaceutically acceptable salt thereof, or combinations thereof, said amount being effective to raise the subject's plasma citrulline level to at least 20 μmol/liter, whereby the effective amount of citrulline, the pharmaceutically acceptable salt thereof, or combinations thereof is enough to ensure the subject is not suffering from relative hypocitrullinemia.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has suffered trauma that results in aneurysmal subarachnoid hemorrhage (SAH).

### Claim 3 (depends on 1)

The method of claim 1, wherein the citrulline, a pharmaceutically acceptable salt thereof, or a combination thereof is administered in a dose ranging from about 100 mg to about 30,000 mg.

### Claim 4 (depends on 3)

The method of claim 3, wherein the citrulline, a pharmaceutically acceptable salt thereof, or a combination thereof is administered in a dose ranging from about 250 mg to about 1,000 mg.

### Claim 5 (depends on 1)

The method of claim 1, wherein the amount of citrulline is effective to raise the subject's plasma citrulline to at least 25 μmol/liter.

### Claim 6 (depends on 1)

The method of claim 1, wherein the amount of citrulline is effective to raise the subject's plasma citrulline to at least about 37 μmol/liter.