US5032679A
Expired / Lapsed
US
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Heparin fragments as inhibitors of smooth muscle cell proliferation
Assignee: Glycomed Inc
•
Filing: 1989-08-31
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Granted: 1991-07-16
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Expires: 2009-08-31
Abstract
Abstract A glycosaminoglycoside (GAG) composition predominantly of tetrasacchardie units derived from heparin/heparan sulfate has enchanced activity in preventing the proliferation of smooth muscle cells. This GAG preparation is useful in the treatment of diseases characterized by unwanted smooth muscle cell proliferation and activity.
Inventors
- 👤 Brian K. Brandley
- 👤 Lun H. Lam
- 👤 Roger A. Laine
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 12:27
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61P; A61P43/00; C; C07; C07H; C07H11/00; C07H13/00; C07H13/02; C07H13/04; C07H3/00; C07H3/06
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
83 words
A process to prepare a glycosaminoglycoside (GAG) composition useful in preventing or inhibiting the proliferation of smooth muscle cells which method comprises: separating a mixture obtainable by complete nitrous acid depolymerization of mammalian heparin/heparan sulfate into fragments according to molecular size, and recovering the size fraction of the mixture comprised predominantly of fragments which are tetrasaccharide units, the mixture of fragments having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin.
Claim 2
Dependent Claim
83 words
A process to prepare a glycosaminoglycoside (GAG) composition useful in preventing or inhibiting the proliferation of smooth muscle cells which method comprises: separating a mixture obtainable by complete nitrous acid depolymerization of mammalian heparin/heparan sulfate into fragments according to molecular size, and recovering the size fraction of the mixture comprised predominantly of fragments which are tetrasaccharide units, the mixture of fragments having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin.
Claim 3
Dependent Claim
14 words
The process of claim 1 wherein the heparin/heparan sulfate is depolymerized with nitrous acid.
Claim 4
Dependent Claim
14 words
The process of claim 1 wherein the depolymerized fragments are separated using gel filtration.
Claim 5
Dependent Claim
23 words
The process of claim 3 wherein gel filtration is conducted using a column containing Biogel P2, and eluting with 15% V/V acetic acid.
Claim 6
Dependent Claim
10 words
A GAG composition prepared by the process of claim 1.
Claim 7
Dependent Claim
9 words
The GAG composition of claim 5 conjugated to label.
Claim 8
Dependent Claim
38 words
A pharmaceutical composition useful in the treatment of conditions characterized by unwanted smooth muscle cell proliferation, which composition comprises an effective amount of the GAG composition of claim 5 in admixture with at least one pharmaceutically acceptable excipient.
Claim 9
Dependent Claim
39 words
A method to treat a condition characterized by unwanted smooth muscle cell proliferation, which method comprises administering to a subject in need of such treatment an effective amount of the composition of claim 5 or a pharmaceutical composition thereof.
Claim 10
Dependent Claim
15 words
The method of claim 8 wherein the condition is a result of surgery or trauma.
Claim 11
Dependent Claim
30 words
The method of claim 8 wherein the condition is selected from the group consisting of Goodpasture's syndrome, acute glomerulonephritis, neonatal pulmonary hypertension, asthma, acute pulmonary hypertension and renal vascular hypertension.
Claim 12
Dependent Claim
11 words
The method of claim 8 wherein the composition is administered intravenously.
Claim 13
Dependent Claim
17 words
The method of claim 9 wherein the composition is administered topically or at the location of trauma.
Claim 14
Dependent Claim
44 words
A method to diagnose a deficiency or excess in antiproliferative oligosaccharides in a mammalian subject which method comprises assessing in a biological sample taken from the subject the level of oligosaccharide competitive in an immunoassay with the composition of claim 5 in labeled form.
Claim 15
Dependent Claim
103 words
A compound obtainable by isolation from depolymerized heparin which is a hexasaccharide or tetrasaccharide, or salt thereof, capable of preventing or inhibiting the proliferation of smooth muscle cells, the compound having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin, wherein the compound has the following structural formula: ##STR5## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C), and * indicates that the associated C (carbon 5) can be in either the R or S configuration.
Claim 16
Dependent Claim
103 words
A compound obtainable by isolation from depolymerized heparin which is a hexasaccharide or tetrasaccharide, or salt thereof, capable of preventing or inhibiting the proliferation of smooth muscle cells, the compound having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin, wherein the compound has the following structural formula: ##STR5## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C), and * indicates that the associated C (carbon 5) can be in either the R or S configuration.
Claim 17
Dependent Claim
7 words
The compound of claim 14 wherein n=1.
Claim 18
Dependent Claim
14 words
The compound of claim 14 which is selected from the group consisting of: ##STR6##
Claim 19
Dependent Claim
80 words
The compound isolable from digested heparin which compound has a higher activity for preventing or inhibiting the proliferation of smooth muscle cells and a lower antithrombotic activity as compared with commercial heparin, which compound has the formula: ##STR7## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C) and * indicates that the associated C (carbon 5) can be in either the R or S configuration.
Claim 20
Dependent Claim
80 words
The compound isolable from digested heparin which compound has a higher activity for preventing or inhibiting the proliferation of smooth muscle cells and a lower antithrombotic activity as compared with commercial heparin, which compound has the formula: ##STR7## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C) and * indicates that the associated C (carbon 5) can be in either the R or S configuration.
Claim 21
Dependent Claim
14 words
The compound of claim 17 wherein the reducing or non-reducing terminal sugar is deleted.
Claim 22
Dependent Claim
7 words
The compound of claim 17 wherein n=1.
Claim 23
Dependent Claim
14 words
The compound of claim 17 which is selected from the group consisting of: ##STR8##
Claim 24
Dependent Claim
37 words
A pharmaceutical composition useful in the treatment of conditions characterized by unwanted smooth muscle cell proliferation, which composition comprises an effective amount of the compound of claim 14 in admixture with at least one pharmaceutically acceptable excipient.
Claim 25
Dependent Claim
39 words
A method to treat a condition characterized by unwanted smooth muscle cell proliferation, which method comprises administering to a subject in need of such treatment an effective amount of the compound of claim 14 or a pharmaceutical composition thereof.
Claim 26
Dependent Claim
15 words
The method of claim 22 wherein the condition is a result of surgery or trauma.
Claim 27
Dependent Claim
17 words
The method of claim 23 wherein the compound is administered topically or at the location of trauma.
Claim 28
Dependent Claim
11 words
The method of claim 22 wherein the compound is administered intravenously.
Claim 29
Dependent Claim
30 words
The method of claim 22 wherein the condition is selected from the group consisting of Goodpasture's syndrome, acute glomerulonephritis, neonatal pulmonary hypertension, asthma, actue pulmonary hypertension and renal vascular hypertension.
Claim 30
Dependent Claim
44 words
A method to diagnose a deficiency or excess in antiproliferative GAG in a mammalian subject which method comprises assessing in a biological sample taken from the subject the level of GAG competitive in an immunoassay with the compound of claim 14 in labeled form.
References Cited (Backward Citations)
US4401662A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-07-15 | 1995-01-14 | 1995-07-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-07-15 | 1999-01-14 | 1999-07-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-07-15 | 2003-01-14 | 2003-07-16 | $7700.00 | Window Closed / Lapsed |