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SYNTHESIS AND TESTING OF A NEW CLASS OF HEPARINOIDS

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 16732
Amount: $50,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1991
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
1161 Research Blvd
St Louis, MO 63119
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 Toce, Joseph A
 Principal Investigator
 (314) 997-7200
Business Contact
 1 R43 HL47230-01
Phone: () -
Research Institution
N/A
Abstract

THE GOAL OF THIS PROJECT IS TO DEVELOP A THERAPEUTIC AGENT WHICH WOULD REPLACE HEPARIN. ALTHOUGH HEPARIN IS THE BEST DRUG FOR TREATMENT OF THROMBOEMBOLIC DISEASE, IT IS UNSTABLE IF ADMINISTERED ORALLY AND MUST THEREFORE BE ADMINISTERED BY THE INTRAVENOUS OR SUBCUTANEOUS ROUTE. IN ADDITION, THE THROMBOCYTOPENIA AND BOTH BLEEDING AND THROMBOSIS, WHICH CAN EMERGE AS COMPLICATIONS OF THIS THERAPY, REMAIN A CLINICAL PROBLEM. RECENTLY, IN A PRELIMINARY REPORT, A GROUP OF SULFONATED BISLACTOBIONIC ACID AMINES HAVE BEEN DEMONSTRATED TO POSSESS ANTICOAGULANT AND ANTIOCCLUSIVE PROPERTIES COMPARABLE TO THOSE CURRENTLY ATTAINABLE WITH COMMERCIAL HEPARIN. STARTING WITH COMPOUNDS SUCH AS MALTOSE AND CELLOBIOSE, THE DISACCHARIDE IS OXIDIZED AND CONDENSED WITH SHORT CHAIN DIAMINES AND THEN SULPHONATED. OUR FIRM PRODUCES LARGE QUANTITIES OF LACTOBIONIC ACID FOR STABILIZATION OF ERYTHROMYCIN AND ORGANS FOR TRANSPLANT. DURING A LITERATURE SEARCH, WE FOUND THAT SULPHONATED BIS-LACTOBIONIC ACID AMINES ARE POTENTIAL ANTICOAGULANTS. IN HEPARIN, THE 3-0'-SULPHATE ON THE MIDDLE SUGAR IS ESSENTIAL FOR ANTICOAGULANT ACTIVITY. WE WILL PRODUCE CARBOHYDRATES OF VARIOUS STRUCTURE WHICH MAY HAVE AN IMPROVED HEPARIN-LIKE ACTIVITY. THE COMPOUNDS WILL BE INITIALLY TESTED FOR ANTICOAGULANT PROPERTIES IN PHASE I AND, LATER IN PHASE II, THEIR ANTITHROMBOTIC ACTIVITY WILL BE EVALUATED. THE ADVANTAGE OF USING MALTOSE AS A BEGINNING DISACCHARIDE IS THAT IT MAY NOT BE DIGESTED TO THE SAME DEGREE AS OTHER SUGARS. CELLOBIOSE IS ANOTHER STARTING DISACCHARIDE WHICH MAY NOT BE CLEAVED BY MAMMALIAN DIGESTIVE ENZYMES. ALSO, THE COMPOUNDS ARE RATHER SMALL, SOLUBLE AND MAY BE READILY ABSORBED. THESE SMALL POLYMERS ARE ALSO NON-TOXIC. ANTICOAGULANT PROPERTIES OF THE FINAL COMPOUNDS GENERATED WILL BE EXAMINED FOR THEIR ABILITY TO PROLONG THE ACTIVATED PARTIAL THROMBOPLASTIN TIME AND THE THROMBIN TIME. THE STANDARD WILL BE HEPARIN, 175 UNITS/MG. DR. TOLLEFSEN, ONE OF THE CONSULTANTS, WILL EXAMINE THE EFFECTS OF ACTIVE COMPOUNDS ON THE RATE OF THROMBIN INHIBITION BY PURIFIED ANTITHROMBIN III AND HEPARIN COFACTOR II AS ESTABLISHED IN HIS LABORATORY.

* Information listed above is at the time of submission. *

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