# US 5,705,178 A · Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers

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- Number: US 5,705,178 A
- Document ID: US5705178A
- Status: Granted
- Kind: A
- Application number: 08/164,266
- Filed: 1993-12-08
- Granted: 1998-01-06
- Earliest claimed: 1991-05-31
- Assignees: Gliatech, Inc.
- Inventors: Dikla Roufa; Adrian Harel; Robert C. A. Frederickson; George T. Coker, III
- Web page: https://patentgrep.com/patent/US5705178A

## CPC

- A61K 31/734: Alginic acid
- A61K 31/727: Heparin; Heparan
- A61K 31/728: Hyaluronic acid
- A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence)
- A61K 31/738: Cross-linked polysaccharides
- A61K 38/1703: {from vertebrates}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61L 27/20: Polysaccharides
- A61L 27/34: Macromolecular materials
- A61L 31/042: {Polysaccharides}
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)

## Abstract

The present invention relates to the discovery that biocompatible anionic polymers can effectively inhibit fibrosis, scar formation, and surgical adhesions. Anionic polymers for use in the invention include but are not limited to natural proteoglycans, and the glycosaminoglycan moieties of proteoglycans. Additionally, anionic carbohydrates and other anionic polymers may be used. The anionic polymers dextran sulfate and pentosan polysulfate are preferred. In a more preferred embodiment, dextran sulfate, in which the sulfur content is greater than about 10% by weight, may be used. In a more preferred embodiment, the average molecular weight is about 40,000 to 500,000 Daltons. The present invention further provides compositions and methods to inhibit glial cell invasion, detrimental bone growth and neurite outgrowth. In a preferred embodiment, the inhibitory compositions further comprise an adhesive protein.

## Claims

### Claim 1

A method for inhibiting neurite outgrowth comprising administering to a site an animal in which inhibition of neurite outgrowth is desired, a composition comprising an amount of dextran sulfate effective to inhibit neurite outgrowth, in which the sulfur content of the dextran sulfate is greater than about 5%.

### Claim 2 (depends on 1)

The method according to claim 1 in which the animal has a tumor of nerve tissue, neuroma, or overproduction of nerve-growth promoting factors as compared to normal levels of nerve growth promoting factors in the animal.

### Claim 3 (depends on 1)

The method according to claim 1, in which the average molecular weight of the dextran sulfate is about 40,000 to 500,000 Daltons.

### Claim 4

A method for treating a neuroma or inhibiting neuroma formation comprising administering to a site in an animal in which treatment of neuroma or inhibition of neuroma formation is desired, a composition comprising an amount of dextran sulfate effective to treat neuroma or to inhibit neuroma formation, in which the sulfur content of the dextran sulfate is greater than about 5%.

### Claim 5 (depends on 1, 2)

The method according to claims 1, 2, or 4 in which the sulfur content of the dextran sulfate is greater than about 10%.

### Claim 6 (depends on 1, 4)

The method according to claim 1 or 4 in which the animal is a mammal.

### Claim 7 (depends on 6)

The method according to claim 6 in which the mammal is a human.