US4727063A
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US
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Depolymerized and supersulfated heparin, process for its preparation and pharmaceutical compositions
Assignee: Recordati Industria Chimica e Farmaceutica SpA
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Filing: 1985-05-24
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Granted: 1988-02-23
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Expires: 2005-05-24
Abstract
Abstract Novel depolymerized and supersulfated heparin having a molecular weight comprised between 2000 and 9000 and a sulfation degree of at least 2.5, in which all of the primary hydroxy groups are sulfated; a process for its preparation by reacting a heparin of natural origin, or a fraction thereof with a sulfuric acid/chlorosulfonic acid mixture; and pharmaceutical compositions containing it as active ingredient, having potential antithrombotic, hypolipemic and fibrinolytic activity and useful in the prevention of thrombosis and for the treatment of atherosclerosis.
Inventors
- 👤 Annamaria Naggi
- 👤 Giangiacomo Torri
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:24
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61P; A61P3/00; A61P3/06; A61P7/00; A61P7/02; A61P7/04; C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0075
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
59 words
A depolymerized and supersulfated heparin having a molecular weight between 2000 and 9000 and a sulfation degree of at least 2.5, represented by the following formula ##STR11## wherein A represents H and SO 3 - , B represents SO 3 - and COCH 3 and m is an integer from 4 to 15; or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
59 words
A depolymerized and supersulfated heparin having a molecular weight between 2000 and 9000 and a sulfation degree of at least 2.5, represented by the following formula ##STR11## wherein A represents H and SO 3 - , B represents SO 3 - and COCH 3 and m is an integer from 4 to 15; or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
16 words
A depolymerized and supersulfated heparin as claimed in claim 1, in form of its sodium salt.
Claim 4
Dependent Claim
16 words
A depolymerized and supersulfated heparin as claimed in claim 1, in form of its calcium salt.
Claim 5
Dependent Claim
155 words
A depolymerized and supersulfated heparin having the formula as in claim 1, wherein m is as defined in claim 1 B is a COCH 3 group in 0 to about 30% of the m disaccharide units, according to the percent of acetyl group existing in the commercial heparin from which the supersulfated heparin derives, and a SO 3 - group in the remaining disaccharide units; the substituent A in the position 3 of the glucosamine subunit is SO 3 - in at least 30% of the m disaccharide units and hydrogen in the remaining ones; the substituent A in the position 2 of the uronic acid subunit is SO 3 - in at least 50% of the m disaccharide units and hydrogen in the remaining ones; the substituent A in the position 3 of the uronic acid subunit is prevalently hydrogen, but it can be SO 3 - in some of the m disaccharide units.
Claim 6
Dependent Claim
155 words
A depolymerized and supersulfated heparin having the formula as in claim 1, wherein m is as defined in claim 1 B is a COCH 3 group in 0 to about 30% of the m disaccharide units, according to the percent of acetyl groups existing in the commercial heparin from which the supersulfated heparin derives, and a SO 3 - group in the remaining disaccharide units; the substituent A in the position 3 of the glucosamine subunit is SO 3 - in at least 50% of the m disaccharide units and hydrogen in the remaining ones; the substituent A in the position 2 of the uronic acid subunit is SO 3 - in at least 70% of the m disaccharide units and hydrogen in the remaining ones; the substituent A in the position 3 of the uronic acid subunit is prevalently hydrogen, but it can be SO 3 - in some of the m disaccharide units.
Claim 7
Dependent Claim
26 words
A depolymerized and supersulfated having a molecular weight between 2000 and 9000 and a sulfation degree of at least 2.5, characterized by the dominating structure ##STR12##
Claim 8
Dependent Claim
26 words
A depolymerized and supersulfated having a molecular weight between 2000 and 9000 and a sulfation degree of at least 2.5, characterized by the dominating structure ##STR12##
Claim 9
Dependent Claim
17 words
A depolymerized and supersulfated heparin according to claim 6, having a sulfation degree of at least 2.8±0.1.
Claim 10
Dependent Claim
18 words
A depolymerized and supersulfated heparin according to claim 6, having a sulfation degree of from 3.0±0.1 to 3.3±0.1
Claim 11
Dependent Claim
92 words
A process for the preparation of a heparin as claimed in claims 1, 2 or 3, in which a heparin of natural origin or a fraction thereof is treated with a mixture of sulfuric acid and chlorosulfonic acid in a ratio sulfuric acid:chlorosulfonic acid of from 1:4 to 4:1 and at a concentration of said acids of at least 95% by weight, at a temperature of from -20° to 40° C. and the product thus obtained is isolated as an alkali metal salt thereof or converted into a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
17 words
A process as claimed in claim 9, in which the ratio sulfuric acid:cholorsulfonic acid is about 2:1.
Claim 13
Dependent Claim
19 words
A process as claimed in claim 9 in which the depolymerized and supersulfated heparin is isolated as sodium salt.
Claim 14
Dependent Claim
32 words
A process as claimed in claim 9 in which the depolymerized and supersulfated heparin obtained has a sulfation degree at least 20% higher than that of the starting heparin or fraction thereof.
Claim 15
Dependent Claim
45 words
A process as claimed in claim 9 in which heparin is added to the acids mixture at a temperature lower than -3° C., and the reaction is carried out for about one hour at less than -3° C. and about one hour at room temperature.
Claim 16
Dependent Claim
37 words
A process as claimed in claim 9 in which diluted sulfuric acid, in an amount of from about 0.2 to about 1.5 g of sulfuric acid per gram of starting heparin, is added to the reaction mixture.
Claim 17
Dependent Claim
18 words
A process as claimed in claim 14 in which said sulfuric acid is at a dilution of 70-85%.
Claim 18
Dependent Claim
43 words
A pharmaceutical composition having potential antithrombotic action and hypolipemic and fibrinolytic activity in dosage unit form comprising from 1 to 1500 mg of a depolymerized and supersulfated heparin as claimed in one of claims 1 to 3 in admixture with a pharmaceutical carrier.
Claim 19
Dependent Claim
31 words
A pharmaceutical composition for the treatment of atherosclerosis and the prevention for thrombosis, comprising, as active ingredient, a depolymerized and supersulfated heparin as claimed in one of claims 1 to 3.
References Cited (Backward Citations)
US2697093A
Cited
US3578657A
Cited
US3951949A
Cited
GB2002406A
Cited
US4303651A
Cited
US4281168A
Cited
US4266077A
Cited
FR2474508A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-02-22 | 1991-08-24 | 1992-02-23 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-02-22 | 1995-08-24 | 1996-02-23 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-02-22 | 1999-08-24 | 2000-02-23 | $7700.00 | Window Closed / Lapsed |