Hmmmmm..... hadn't noticed, but a CIP of 5,605,938 has also issued, 11/30/99........
US5994325: Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers
The present invention relates to the discovery that biocompatible anionic polymers can effectively
inhibit fibrosis, scar formation, and surgical adhesions. The invention is predicated on the discovery
that anionic polymers effectively inhibit invasion of cells associated with detrimental healing
processes, and in particular, that the effectiveness of an anionic polymer at inhibiting cell invasion
correlates with the anionic charge density of the polymer. Thus the present invention provides a large
number of materials for use in methods of inhibiting fibrosis and fibroblast invasion. 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 provides compositions and methods to
inhibit fibrosis and scarring associated with surgery. The 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.
What is claimed is:
1. A composition comprising an amount of pentosan polysulfate effective to inhibit fibrosis in a
mammal, and a pharmaceutically acceptable carrier.
2. The composition according to claim 1 in which the carrier is selected from the group consisting of a
solid carrier and a semi-solid carrier.
3. A method for inhibiting fibrosis of a lesion in a mammal comprising administering an amount
effective to inhibit fibrosis of a composition comprising pentosan polysulfate and a pharmaceutically
acceptable excipient or carrier, to the site of the lesion.
4. A method for inhibiting fibrosis of a lesion in a mammal comprising administering a composition to
the site of a lesion in a mammal, said composition comprising (a) an amount of pentosan polysulfate
effective to inhibit fibrosis, and (b) an amount of an adhesive protein effective to anchor the pentosan
polysulfate at the site of the lesion.
5. A method for inhibiting fibrosis of a lesion in a mammal following a laminectomy comprising
administering a composition comprising an amount of pentosan polysulfate and a pharmaceutically
acceptable excipient or carrier effective to inhibit fibrosis to a laminectomy site in a mammal.
6. A composition comprising an amount of cross-linked pentosan polysulfate effective to inhibit fibrosis
in a mammal, and a pharmaceutically acceptable solution, which cross-linked pentosan polysulfate
demonstrates greater viscosity in solution than the same amount of non-cross-linked pentosan
polysulfate in the same volume of solution.
7. The composition according to claim 2 in which the carrier is a semi-solid pharmaceutical carrier
selected from the group consisting of native collagen gel, denatured collagen gel and dextran gel.
8. The method according to claim 4 in which the adhesive protein is selected from the group consisting
of fibrin, mussel polyphenolic adhesion protein, barnacle polyphenolic adhesion protein, oyster
polyphenolic protein, and chemically polymerized peptide from an adhesion protein.
9. The method according to claim 3 or 4 in which the lesion is a surgical lesion.
10. The method according to claim 3 or 4 in which the lesion results from traumatic injury.
11. The method according to claim 9 in which the surgical lesion results from a laminectomy, fallopian
tube surgery, plastic surgery, or surgery to treat temporomandibular joint dysfunction.
12. The method according to claim 5 in which the composition further comprises a semi-solid
pharmaceutically acceptable carrier. |
