# US 9,040,040 B2 · Enzyme combinations to reduce brain tissue swelling

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- Number: US 9,040,040 B2
- Document ID: US9040040B2
- Status: Granted
- Kind: B2
- Application number: 13/900,755
- Filed: 2013-05-23
- Published: 2013-10-03
- Granted: 2015-05-26
- Earliest claimed: 2010-11-23
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University in the City of New York
- Inventors: Benjamin Simon Elkin; Barclay Morrison, III; John Desmond Finan
- Web page: https://patentgrep.com/patent/US9040040B2

## CPC

- A61K 38/54: Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
- A61K 38/46: Hydrolases (3)
- A61K 38/465: {acting on ester bonds (3.1), e.g. lipases, ribonucleases}
- A61K 38/47: acting on glycosyl compounds (3.2), e.g. cellulases, lactases
- A61K 38/51: Lyases (4)
- 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)

## Abstract

Tissue fixed charge density (FCD) is identified as another potential therapeutic target for reducing brain tissue swelling. Reduction of the FCD could reduce the thermodynamic force driving water entry into the brain. The present invention discloses chondroitinase ABC (ChABC) reduces tissue FCD and reduces tissue swelling, indicating that it may be an effective treatment to reduce edema and control intracranial pressure.

## Claims

### Claim 1

A method of reducing brain tissue swelling in a subject in need thereof, comprising the step of administering to the subject a composition comprising an enzyme that digests chondroitin sulfate proteoglycans, an enzyme that digests heparin sulfate proteoglycans, and an enzyme that digests DNA.

### Claim 2 (depends on 1)

The method of claim 1, wherein the enzyme that digests chondroitin sulfate proteoglycans is chondroitinase ABC.

### Claim 3 (depends on 1)

The method of claim 1, wherein the enzyme that digests heparin sulfate proteoglycans is heparinase.

### Claim 4 (depends on 3)

The method of claim 3, wherein the heparinase is heparinase I or heparinase III.

### Claim 5 (depends on 1)

The method of claim 1, wherein the enzyme that digests DNA is DNase I.