Bergonzini G L, Bianchini P, Mascellani G, Osima B, Parma B, Volpi N
Opocrin S.p.A., Research Laboratories, Corlo-Modena, Italy.
Arzneimittelforschung. 1992 Nov;42(11):1322-8.
Native heparin (CAS 9005-49-6) and its two new fragments, low molecular weight heparin (LMW-H, 5 kDa) and oligo-heparin (oligo-H, 2 kDa) obtained by radical degradation were characterized as to their physicochemical properties. Heparin fragments differ from unfractionated heparin only in molecular weight. The pharmacokinetics and some pharmacological effects, bleeding and antithrombotic activity, of the three different molecular weight heparins were investigated. The plasma concentrations were determined by an amidolytic method which measures inhibiting effect on factor Xa. The blood levels of each substance were derived from their in vitro calibration curves. The examination of the pharmacokinetics parameters allowed to evaluate the differences in the bioavailability, absorption rate and elimination mechanisms between the three different heparins. The bioavailability, the absorption rate and the distribution of the molecules of heparins in biological compartments depend on the molecular weight. LMW-H and oligo-H exhibit greater antithrombotic activity than unfractionated heparin when administered subcutaneously. The pharmacokinetic behaviour of oligo-H considerably differs from that of unfractionated heparin and LMW-H. This new drug is able to bind cells and plasma proteins differently from heparin and LMW-H. The capacity of oligo-H to bind smooth muscle cells and to interact with myosin is discussed in relation to the bleeding effect.
天然肝素（CAS 9005-49-6）及其通过自由基降解获得的两个新片段，低分子量肝素（LMW-H，5 kDa）和寡聚肝素（oligo-H，2 kDa），对其理化性质进行了表征。肝素片段与未分级肝素的区别仅在于分子量。研究了三种不同分子量肝素的药代动力学以及一些药理作用、出血和抗血栓活性。血浆浓度通过一种测量对因子Xa抑制作用的酰胺水解法测定。每种物质的血药浓度来自其体外校准曲线。药代动力学参数的研究有助于评估三种不同肝素在生物利用度、吸收速率和消除机制方面的差异。肝素分子在生物区室中的生物利用度、吸收速率和分布取决于分子量。皮下给药时，LMW-H和oligo-H比未分级肝素表现出更大的抗血栓活性。oligo-H的药代动力学行为与未分级肝素和LMW-H有很大不同。这种新药与肝素和LMW-H不同，能够以不同方式结合细胞和血浆蛋白。结合出血效应讨论了oligo-H结合平滑肌细胞和与肌球蛋白相互作用的能力。
