US5403827A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Process for preparing epoxy-heparides, the products obtained and pharmaceutical compositions containing them
Assignee: Laboratori Derivati Organici SpA
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Filing: 1993-11-02
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Granted: 1995-04-04
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Expires: 2013-11-02
Abstract
Abstract There is provided a process for preparing epoxy-heparide polysaccharides of formula (I): ##STR1## wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute a polysaccharide chain bonded to said ring A by a glucoside, and one of R and R' is H when the ring A is in the terminal position of said polysaccharide chains, and said heparide has a COCH 3 to COOH ratio of 0.5, said process comprising a) N-desulfation of heparin to obtain the corresponding heparamine; b) acetylation of the heparamine of step (a) to obtain the corresponding heparide; c) epoxidation of the heparide of step (b) by treating the heparide with hydrogen peroxide in an alkaline reaction medium at pH 12-14; and d) cooling the solution obtained in step (c) to a temperature of between 15° and 25° C. and adjusting the pH to between 5.8 and 6.0.
Inventors
- 👤 Luigi De-Ambrosi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 00:37
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/715; A61P; A61P7/00; A61P7/02; A61P9/00; A61P9/10; C; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0075
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
158 words
A process for preparing epoxyheparide polysaccharides of formula (I): ##STR6## wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute a polysaccharide chain bonded to said ring A by a glucoside, and one of R and R' is H when the ring A is in the terminal position of said polysaccharide chains and said heparide has a COCH 3 to COOH ratio of 0.5 said process comprising a) N-desulphation of heparin to obtain the corresponding heparamine; b) acetylation of the heparamine of step (a) to obtain the corresponding heparide; c) expoxidation of the heparide of step (b) by treating the heparide with hydrogen peroxide in an alkaline reaction medium at pH 12-14; and d) cooling the solution obtained in step (c) to a temperature of between 15° and 25° C. and adjusting the pH to between 5.8 and 6.0.
Claim 2
Dependent Claim
158 words
A process for preparing epoxyheparide polysaccharides of formula (I): ##STR6## wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute a polysaccharide chain bonded to said ring A by a glucoside, and one of R and R' is H when the ring A is in the terminal position of said polysaccharide chains and said heparide has a COCH 3 to COOH ratio of 0.5 said process comprising a) N-desulphation of heparin to obtain the corresponding heparamine; b) acetylation of the heparamine of step (a) to obtain the corresponding heparide; c) expoxidation of the heparide of step (b) by treating the heparide with hydrogen peroxide in an alkaline reaction medium at pH 12-14; and d) cooling the solution obtained in step (c) to a temperature of between 15° and 25° C. and adjusting the pH to between 5.8 and 6.0.
Claim 3
Dependent Claim
88 words
Epoxy-heparide polysaccharides of formula (I): ##STR7## which are prepared by the process of claim 1, wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute polysaccharide chains bonded to said ring A by a glucoside bond, and one of R and R' is H when said ring A is in the terminal position of said polysaccharide chains and said heparide has a COCH 3 to COOH ratio of 0.5.
Claim 4
Dependent Claim
32 words
A process as claimed in claim 1, wherein said alkaline reaction medium is an aqueous solution containing an alkaline substance chosen from the group consisting of NaOH, KOH and NH 4 OH.
Claim 5
Dependent Claim
21 words
A process as claimed in claim 1, wherein said epoxidation is conducted at a temperature of between 40° and 80° C.
Claim 6
Dependent Claim
44 words
A process as claimed in claim 1, wherein said hydrogen peroxide is of 37% concentration and is added in a quantity of between 0.5 and 1 ml per 10 g of N-desulphated and acetylated heparin over a time of between 1 and 4 hours.
Claim 7
Dependent Claim
116 words
Pharmaceutical composition for the therapy of human thrombosis and atherosclerosis, said pharmaceutical composition comprising effective amounts for the treatment of atherosclerosis and thrombosis of epoxy-heparide polysaccharides of formula (I) ##STR8## which are prepared by the process of claim 1, wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute polysaccharide chains bonded to the ring A by a glucoside bond, and one of R and R' is H when the ring A is in the terminal position of said polysaccharide chains, said heparide having a COCH 3 to COOH ratio of 0.5, and a pharmaceutically acceptable diluent.
Claim 8
Dependent Claim
121 words
Therapeutic method for the treatment of human thrombosis and atherosclerosis consisting in the administration to a human in need of such treatment of an effective amount for the treatment of atherosclerosis and thrombosis of epoxy-heparide polysaccharides of formula (I) ##STR9## which are prepared by the process of claim 1, wherein A is a pyran ring with substituents 1 and 4 in the axial position and 5 in the equatorial position, and R and R' are hexosamines which constitute polysaccharide chains bonded to the ring A by a glucoside bond, and one of R and R' is H when the ring A is in the terminal position of said polysaccharide chains, said heparide having a COCH 3 to COOH ratio of 0.5.
Claim 9
Dependent Claim
27 words
Therapeutic method according to claim 7, comprising administration of 100 mg/day of epoxy heparide polysaccharides of formula (I) which are prepared by the process of claim 1.
Claim 10
Dependent Claim
12 words
Therapeutic method according to claim 8 wherein a human thrombosis is treated.
Claim 11
Dependent Claim
10 words
Therapeutic method according to claim 8 wherein atherosclerosis is treated.
Claim 12
Dependent Claim
14 words
A composition as defined in claim 6 wherein the effective amount is 100 mg.
Claim 13
Dependent Claim
14 words
A method as defined in claim 7 wherein the effective amount is 100 mg/day.
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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) | 1998-04-03 | 1998-10-03 | 1999-04-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-04-03 | 2002-10-03 | 2003-04-04 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-04-03 | 2006-10-03 | 2007-04-04 | $7700.00 | Window Closed / Lapsed |