Preparation and anticoagulation activity of sodium cellulose sulfate.
Semi-synthesis of cellulose sulfate sodium (Na-MCS) was carried out by sulfation of microcrystalline cellulose (MCC) with chlorosulfonic acid-dimethylformamide complex as sulfating agent. As shown by FT-IR, NMR spectroscopy, and elemental analysis, the sulfation occurred mainly at C6, partially at C2, and no substitution at C3. The substitution degree ranged from 1.10 to 1.70 and the average molecular weight is between 1.1 and 3.5 x 10(4)Da. The anticoagulant efficacy and its possible mechanism were investigated using in vitro, in vivo coagulation assays and amidolytic tests in comparison with heparin. Results indicated that Na-MCS exhibited higher anticoagulation activity based on activated partial thromboplastin time (APTT) assay and prolonged the thrombin time (TT) to a lesser extent than heparin. No effect was detected on the prothrombin time (PT). Subcutaneous administration of Na-MCS to mice increased the clotting time (CT) in a moderate dose-dependent manner with a longer duration. Na-MCS exhibited anticoagulation activity mainly by accelerating the inhibition of antithrombin III (AT-III) on coagulation factors FIIa and FXa in plasma.
Wang
Zhao Mei
ZM
Research Institute of Light Industry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. wangzm@scut.edu.cn
Li
Lin
L
Zheng
Bi Sheng
BS
Normakhamatov
Nodirali
N
Guo
Si Yuan
SY
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000990:Antithrombin III / Q000037:antagonists & inhibitors; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D004577:Electron Probe Microanalysis; D015951:Factor Xa / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008970:Molecular Weight; D009391:Nephelometry and Turbidimetry; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013455:Sulfur / Q000032:analysis; D013918:Thrombin Time; D013997:Time Factors
D000925:Anticoagulants; D013455:Sulfur; D000990:Antithrombin III; D011516:Prothrombin; C025337:Factor IIa; D002482:Cellulose; D006493:Heparin; C020254:cellulose sulfate; D015951:Factor Xa