Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1996-10-01
1998-06-16
Fonda, Kathleen K.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 21, 536124, 514 56, C07H 100, C07H 504, A61K 31725
Patent
active
057672695
ABSTRACT:
The present invention generally relates to a processes for preparing low affinity, low molecular weight heparins (LA-LWM-heparins) which are endowed with pharmacological and therapeutic properties that are surprisingly advantageous. In one embodiment, the process comprises: (1) nitrous acid depolymerization of unfractionated heparin to yield low molecular weight heparin (LMWH); (2) oxidation of the resulting LMWH to open the ring structures the nonsulfated uronic acid moieties using, for example, sodium periodate; and (3) reduction of the oxidized LMWH to reduce the aldehydes (to alcohols) formed during the depolymerization and oxidation steps using, for example, sodium borohydride. The resulting LA-LMW-heparins are capable of inactivating thrombin bound to fibrin within a thrombus or clot, whereby the ability of clot-bound thrombin to catalytically promote further clot accretion is substantially diminished or eliminated. As such, the resulting LA-LMW-heparins are useful for preventing thrombosis in the circuit of cardiac bypass apparatus and in patients undergoing renal dialysis, and for treating patients suffering from or at risk of suffering from thrombus-related cardiovascular conditions, such as unstable angina, acute myocardial infarction (heart attack), cerebrovascular accidents (stroke), pulmonary embolism, deep vein thrombosis, arterial thrombosis, etc.
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Hirsh Jack
Knobloch James E.
Shaklee Patrick N.
Weitz Jeffrey I.
Young Edward
Fonda Kathleen K.
Hamilton Civic Hospitals Research Development Inc.
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