title: Synthesis and anticoagulant activity of polyureas containing sulfated carbohydrates.
abstract: Polyurea-based synthetic glycopolymers containing sulfated glucose, mannose, glucosamine, or lactose as pendant groups have been synthesized by step-growth polymerization of hexamethylene diisocyanate and corresponding secondary diamines. The obtained polymers were characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The nonsulfated polymers showed similar results to the commercially available biomaterial polyurethane TECOFLEX in a platelet adhesion assay. The average degree of sulfation after reaction with SO3 was calculated from elemental analysis and found to be between three and four -OSO3 groups per saccharide. The blood-compatibility of the synthetic polymers was measured using activated partial thromboplastin time, prothrombin time, thrombin time, anti-IIa, and anti-Xa assays. Activated partial thromboplastin time, prothrombin time, and thrombin time results indicated that the mannose and lactose based polymers had the highest anticoagulant activities among all the sulfated polymers. The mechanism of action of the polymers appears to be mediated via an anti-IIa pathway rather than an anti-Xa pathway.
authors.affiliation: Department of Chemistry and ‡Materials Science and Engineering Program, The University of Cincinnati , Cincinnati, Ohio 45221, United States.
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Huang
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Shaw
authors.forename: Eric S
authors.initials: ES
authors.lastname: Mullins
authors.forename: Terence L
authors.initials: TL
authors.lastname: Kirley
authors.forename: Neil
authors.initials: N
authors.lastname: Ayres
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002241:Carbohydrates / Q000737:chemistry*; D002850:Chromatography, Gel; D051379:Mice; D010314:Partial Thromboplastin Time; D010973:Platelet Adhesiveness / Q000187:drug effects; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology*; D011140:Polyurethanes / Q000138:chemical synthesis / Q000494:pharmacology; D011517:Prothrombin Time; D017550:Spectroscopy, Fourier Transform Infrared; D013431:Sulfates / Q000737:chemistry*; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D002241:Carbohydrates; D011108:Polymers; D011140:Polyurethanes; D013431:Sulfates; C045786:polyurea; C062725:Tecoflex