Anti-thromboticum based on polysacharides, method for its preparation and pharmaceutical compositions

Claim 2

An antithrombotically effective heparinoid, which is a mixture of oligo- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, galactosamine, and sulfated and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 2500 and 15,000 daltons and an auxiliary peak and/or shoulder in the range between 15,000 and 60,000 daltons; (b) a specific rotation ([α] D 20 ) between +25° and +80°; (c) a nitrogen content between 1.5 and 4% by weight; (d) a sulphur content between 5 and 7.5% by weight; (e) a content of ionic groups in meq/g between 3 and 5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.6; (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 0.5 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model ) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemorrhagic activity, and (7) half value time which is at least twice as long as that of heparin USP.

Claim 3

Pharmaceutical composition having anticlotting activity which comprises an anticlotting effective amount of a compound of claim 1 in a pharmaceutically acceptable carrier.

Claim 4

An antithrombotically effective heparinoid, which is a mixture of oligo- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, galactosamine, and sulfated and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 2500 and 15,000 daltons; (b) a specific rotation ([α] D 20 ) between +25° and +80°; (c) a nitrogen content between 1.5 and 4% by weight; (d) a sulphur content between 5 and 7.5% by weight; (e) a content of ionic groups in meq/g between 3 and 5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.1; and (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 0.5 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemmorrhagic activity, and (7) half value time which is at least twice as long as that of heparin USP.

Claim 5

An antithrombotically effective heparinoid, which is a mixture of oligo- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, galactosamine, and sulfated and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 2500 and 15,000 daltons; (b) a specific rotation ([α] D 20 ) between +25° and +80°; (c) a nitrogen content between 1.5 and 4% by weight; (d) a sulphur content between 5 and 7.5% by weight; (e) a content of ionic groups in meq/g between 3 and 5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.1; and (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 0.5 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemmorrhagic activity, and (7) half value time which is at least twice as long as that of heparin USP.

Claim 6

An antithrombotically effective heparinoid, which is a mixture of olgio- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, glaactosamine, and sulfated and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 4000 and 10,000 daltons and an average molecular weight of between 5000 and 8000 daltons and an auxiliary peak and/or shoulder in the range between 30,000 and 50,000 daltons with an average molecular weight of about 40,000 daltons; (b) a specific rotation ([α] D 20 ) between +40° and +70°; (c) a nitrogen content between 2.5 and 3.5% by weight; (d) a sulphur content between 5.5 and 6.5% by weight; (e) a content of ionic groups in meq/g between 3.5 and 4.5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.6; (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 1.0 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemorrhagic activity; and (7) half value time which is at least twice as long as that of heparin USP.

Claim 7

An antithrombotically effective heparinoid, which is a mixture of olgio- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, glaactosamine, and sulfated and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 4000 and 10,000 daltons and an average molecular weight of between 5000 and 8000 daltons and an auxiliary peak and/or shoulder in the range between 30,000 and 50,000 daltons with an average molecular weight of about 40,000 daltons; (b) a specific rotation ([α] D 20 ) between +40° and +70°; (c) a nitrogen content between 2.5 and 3.5% by weight; (d) a sulphur content between 5.5 and 6.5% by weight; (e) a content of ionic groups in meq/g between 3.5 and 4.5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.6; (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 1.0 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemorrhagic activity; and (7) half value time which is at least twice as long as that of heparin USP.

Claim 8

An antithrombotically effective heparinoid, which is a mixture of oligo- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, galactosamine, and sulfated and and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 4000 and 10,000 daltons and an average molecular weight of between 5,000 and 8,000 daltons; (b) a specific rotation ([α] D 20 ) between +40° and +70°; (c) a nitrogen content between 2.5 and 3.5% by weight; (d) a sulphur content between 5.5 and 6.5% by weight; (e) a content of ionic groups in meq/g between 3.5 and 4.5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.1; and (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 1.0 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemorrhagic activity, and (7) half value time which is at least twice as long as that of heparin USP.

Claim 9

An antithrombotically effective heparinoid, which is a mixture of oligo- and polysaccharides from residues of glucuronic acid, iduronic acid, glucosamine, galactosamine, and sulfated and and acetylated derivatives thereof, said heparinoid having (a) a molecular weight between 2000 and 40,000 daltons with a main peak between 4000 and 10,000 daltons and an average molecular weight of between 5,000 and 8,000 daltons; (b) a specific rotation ([α] D 20 ) between +40° and +70°; (c) a nitrogen content between 2.5 and 3.5% by weight; (d) a sulphur content between 5.5 and 6.5% by weight; (e) a content of ionic groups in meq/g between 3.5 and 4.5; (f) a content of sulphamido groups in meq/g between 0.5 and 1.5; (g) a glucosamine content in meq/g of 0.5 to 1.5; (h) a galactosamine content in meq/g of 0.0 to 0.1; and (i) an idose (iduronic acid)/glucose (glucuronic acid)-ratio of 1.0 to 3; said heparinoid having (1) an anti-coagulation activity (USP) of less than 10 international units per mg; (2) a negligible thrombin activity (less than 1% of that of heparin USP); (3) an anti-X a activity of less than 20% of that of heparin, usually between 2.5 and 15%; (4) an anti-thrombotic activity (Umetsu model) with an ID 50 of roughly 2 to 8 mg/kg i.v.; (5) a bleeding activity which hardly increases at all over a wide dosage range (up to 300 mg/kg i.v.); (6) a benefit/risk ratio which is 10-40 times more favourable than that for heparin USP having regard to the anti-thrombotic activity as compared with haemorrhagic activity, and (7) half value time which is at least twice as long as that of heparin USP.

Claim 10

Pharmaceutical composition having anticlotting activity which comprises an anticlotting effective amount of a compound of claim 3 in a pharmaceutical acceptable carrier.

Claim 11

Pharmaceutical composition having anticlotting activity which comprises an anticlotting effective amount of a compound of claim 4 in a pharmaceutical acceptable carrier.

Claim 12

Pharmaceutical composition having anticlotting activity which comprises an anticlotting effective amount of a compound of claim 5 in a pharmaceutical acceptable carrier.