US5705177A
Expired / Lapsed
US
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Methods and compositions based on inhibition of cell invasion and fibrosis by anionic polymers
Assignee: TRIAD LLC
•
Filing: 1992-05-29
•
Granted: 1998-01-06
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Expires: 2012-05-29
Abstract
Abstract PCT No. PCT/US92/04474 Sec. 371 Date Jul. 26, 1994 Sec. 102(e) Date Jul. 26, 1994 PCT Filed May 29, 1992 PCT Pub. No. WO92/21354 PCT Pub. Date Dec. 10, 1992The 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.
Inventors
- 👤 Dikla Roufa
- 👤 Adrian Harel
- 👤 Robert C. A. Frederickson
- 👤 George T. Coker, III
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 12:54
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61K31/734; A61K31/726; A61K31/727; A61K31/728; A61K31/737; A61K31/738; A61K38/00; A61K38/16; A61K38/17; A61K38/1703; A61K38/39; A61L; A61L27/00; A61L27/14; A61L27/20; A61L27/28; A61L27/34; A61L31/00; A61L31/04; A61L31/042; A61P; A61P17/00; A61P17/02; A61P19/00; A61P25/00; A61P3/00; A61P31/00; A61P31/04; A61P31/12; A61P35/00; A61P39/00; A61P41/00; A61P43/00; Y; Y10; Y10S; Y10S530/00; Y10S530/855; Y10S530/857; Y10S623/00; Y10S623/915; Y10S623/924; Y10S977/00; Y10S977/70; Y10S977/788; Y10S977/789; Y10S977/79; Y10S977/791; Y10S977/793; Y10S977/795; Y10S977/902; Y10S977/904; Y10S977/908; Y10S977/91
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
54 words
A composition comprising: (a) an amount of an anionic polymer selected from the group consisting of pentosan polysulfate and alginate effective to inhibit bone growth at the site of a lesion in an animal; and (b) an amount of an adhesive protein effective to anchor the anionic polymer at the site of the lesion.
Claim 2
Dependent Claim
54 words
A composition comprising: (a) an amount of an anionic polymer selected from the group consisting of pentosan polysulfate and alginate effective to inhibit bone growth at the site of a lesion in an animal; and (b) an amount of an adhesive protein effective to anchor the anionic polymer at the site of the lesion.
Claim 3
Independent Claim
73 words
A method for inhibiting glial cell invasion in an animal comprising administering a composition to the site of a lesion in an animal, said composition comprising (a) an anionic polymer selected from the group consisting of dextran sulfate, pentosan polysulfate and alginate in an amount which is effective to inhibit said glial cell invasion; and (b) an amount of adhesive protein effective to anchor the anionic polymer at the site of the lesion.
Claim 4
Independent Claim
73 words
A method for inhibiting glial cell invasion in an animal comprising administering a composition to the site of a lesion in an animal, said composition comprising (a) an anionic polymer selected from the group consisting of dextran sulfate, pentosan polysulfate and alginate in an amount which is effective to inhibit said glial cell invasion; and (b) an amount of adhesive protein effective to anchor the anionic polymer at the site of the lesion.
Claim 5
Dependent Claim
41 words
The method according to claim 2 in which the glial cell invasion is caused by a disease or disorder selected from the group consisting of trauma, surgery, viral infection, bacterial infection, metabolic disease, malignancy, exposure to toxic agents, and hyperplastic situations.
Claim 6
Dependent Claim
14 words
The method according to claim 2 in which the glial cell is an astrocyte.
Claim 7
Dependent Claim
46 words
The composition of claim 1 in which the adhesive protein is selected from the group consisting of fibrin, mussel polyphenolic adhesion protein, barnacle polyphenolic adhesion protein, oyster polyphenolic adhesion protein, chemically polymerized peptide from an adhesion protein and an analog of an adhesion protein produced recombinantly.
Claim 8
Dependent Claim
28 words
An improved implant in which the improvement comprises a coating on the implant of a suitable amount of the composition of claim 1 effective to inhibit bone growth.
Claim 9
Dependent Claim
34 words
The improved implant of claim 6 in which the polymer implant is selected from the group consisting of nephrostomy tube, peritoneal drainage tube, artificial hip joint, artificial heart valve, and peripheral nerve repair prosthesis.
Claim 10
Independent Claim
29 words
A method for inhibiting undesirable bone growth in an animal comprising administering to the animal dextran sulfate in an amount which is effective to inhibit said undesirable bone growth.
Claim 11
Independent Claim
29 words
A method for inhibiting undesirable bone growth in an animal comprising administering to the animal dextran sulfate in an amount which is effective to inhibit said undesirable bone growth.
Claim 12
Independent Claim
60 words
A method for inhibiting undesirable bone growth in an animal comprising administering a composition to the site of a lesion in an animal, said composition comprising (a) dextran sulfate in an amount which is effective to inhibit said undesirable bone growth; and (b) an amount of adhesive protein effective to anchor the dextran sulfate at the site of the lesion.
Claim 13
Independent Claim
60 words
A method for inhibiting undesirable bone growth in an animal comprising administering a composition to the site of a lesion in an animal, said composition comprising (a) dextran sulfate in an amount which is effective to inhibit said undesirable bone growth; and (b) an amount of adhesive protein effective to anchor the dextran sulfate at the site of the lesion.
Claim 14
Dependent Claim
19 words
The method according to claim 8 or 9 wherein the sulfur content is greater than about 10% by weight.
Claim 15
Dependent Claim
23 words
The method according to claim 8 or 9 wherein the average molecular weight of the dextran sulfate is about 40,000 to 50,000 Daltons.
Claim 16
Independent Claim
32 words
A method for inhibiting undesirable bone growth in an animal comprising administering a composition to the animal, said composition comprising a solution of about 2-20 mg/ml of dextran sulfate and denatured collagen.
Claim 17
Independent Claim
32 words
A method for inhibiting undesirable bone growth in an animal comprising administering a composition to the animal, said composition comprising a solution of about 2-20 mg/ml of dextran sulfate and denatured collagen.
Claim 18
Independent Claim
35 words
A method for inhibiting undesirable bone growth in an animal comprising administering to the animal cross-linked dextran sulfate in an amount which is effective to inhibit said undesirable bone growth and a pharmaceutically acceptable carrier.
Claim 19
Independent Claim
35 words
A method for inhibiting undesirable bone growth in an animal comprising administering to the animal cross-linked dextran sulfate in an amount which is effective to inhibit said undesirable bone growth and a pharmaceutically acceptable carrier.
Claim 20
Dependent Claim
17 words
The method according to claim 9 wherein the dextran sulfate is covalently cross-linked to the adhesive protein.
Claim 21
Dependent Claim
47 words
The method according to claim 9 in which the adhesive protein is selected from the group consisting of fibrin, mussel polyphenolic adhesion protein, barnacle polyphenolic adhesion protein, oyster polyphenolic adhesion protein, chemically polymerized peptide from an adhesion protein and an analog of an adhesion protein produced recombinantly.
Claim 22
Dependent Claim
23 words
The method according to claim 12 or 13 wherein the sulfur content of the dextran sulfate is greater than approximately 10% by weight.
Claim 23
Independent Claim
14 words
The method according to 8, or 9 in which the animal is a human.
Claim 24
Independent Claim
14 words
The method according to 8, or 9 in which the animal is a human.
Claim 25
Dependent Claim
20 words
The method according to claim 8 in which said administering is to the site of a lesion in the animal.
Claim 26
Dependent Claim
14 words
The method according to claim 18 in which the lesion is a surgical lesion.
Claim 27
Dependent Claim
14 words
The method according to claim 18 in which the lesion results from traumatic injury.
Claim 28
Dependent Claim
15 words
The method according to claim 19 in which the surgical lesion results from a laminectomy.
Claim 29
Dependent Claim
21 words
The method according to claim 19 in which the surgical lesion results from discectomy or surgery to treat temporomandibular joint dysfunction.
Claim 30
Dependent Claim
33 words
The method of claim 19 in which the surgical lesion results from joint surgery, tendon surgery, thoracic surgery, vascular surgery, cardiac surgery, heart bypass surgery, heart valve replacement surgery, or open heart surgery.
Claim 31
Independent Claim
42 words
A method for inhibiting glial cell invasion in an animal comprising administering to the animal an anionic polymer selected from the group consisting of dextran sulfate, pentosan polysulfate, and alginate in an amount which is effective to inhibit said glial cell invasion.
Claim 32
Independent Claim
42 words
A method for inhibiting glial cell invasion in an animal comprising administering to the animal an anionic polymer selected from the group consisting of dextran sulfate, pentosan polysulfate, and alginate in an amount which is effective to inhibit said glial cell invasion.
Claim 33
Dependent Claim
18 words
The method according to claim 2, 3, 4 or 24 in which the anionic polymer is dextran sulfate.
Claim 34
Dependent Claim
20 words
The method according to claim 24 in which said administering is to the site of a lesion in the animal.
Claim 35
Dependent Claim
41 words
The method according to claim 24 in which the glial cell invasion is caused by a disease or disorder selected from the group consisting of trauma, surgery, viral infection, bacterial infection, metabolic disease, malignancy, exposure to toxic agents, and hyperplastic situations.
Claim 36
Dependent Claim
18 words
The method according to claim 8, 9, 18, or 19 in which the undesirable bone growth follows craniosternostosis.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-01-05 | 2001-07-07 | 2002-01-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-01-05 | 2005-07-07 | 2006-01-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-01-05 | 2009-07-07 | 2010-01-06 | $7700.00 | Window Closed / Lapsed |