Avaliação comparativa da atividade biológica de heparinas não-fracionadas em produtos farmacêuticos

Abstract

Realizou-se a avaliação biológica de potência de heparinas convencionais contra o 5º Padrão IntroduçãoAs heparinas convencionais, não-fracionadas, são usadas clinicamente para profilaxia e tratamento de trombose venosa, devido às suas propriedades anticoagulantes. Recentemente foram desenvolvidas e encontram-se disponíveis as heparinas de baixo peso molecular com eficácia antitrombótica, menos complicações hemorrágicas e redução da freqüência de injeções.Estruturalmente, as heparinas são glicosaminoglicanos sulfatados de peso molecular variável, compostos de unidades de glicosamina e ácido hexurônico, que se alternam unidas por ligações glicosídicas. O polímero apresenta micro-heterogeneidade estrutural devido à sulfatação e acetilação variáveis, bem como a distribuição das unidades de ácido hexurônico, mas a atividade biológica é semelhante.

Evaluation of the changes on hemostatic parameters induced by valdecoxib in male Wistar rats

“…After exactly two minutes, 100 µL of calcium chloride solution (25 mmol/L) was added and the clotting time recorded for each tube. 10 …”

Biological potency evaluation and physicochemical characterization of unfractionated heparins

“…The assay was carried out as described elsewhere. 12,13,16 Three concentrations at 0.2, 0.4 and 0.8 IU/mL were selected according to the linear range of the doseresponse curve of the 5th UHS. The assay was performed in duplicate adding 100 µL of plasma and 100 µL of standard or sample solution of heparin in assay tubes placed in coagulometer at 37°C and incubated for 15 min.…”

“…Samples were prepared by successive dissolution in deuterium oxide (D 2 O 99.9%, Cambridge Isotope Laboratory), frozen, lyophilized before 1 H analyses. 1 H-NMR (400 MHz) 13 C-NMR (100.6 MHz) analyses were performed at 30 °C in D 2 O, chemical shifts being expressed in δ PPM. The proton chemical shifts were identified according to the literature.…”

“…The results were also 3.22% and 1.22% higher compared respectively, to the APTT and AXa, but with significant correlation (P >0.05), following also previously published data. 13 Protamine sulfate or chloride formulations are clinically available and used for the neutralization of heparins. The test was adjusted and performed for the evaluation of the same samples showing differences in the neutralization rates, mainly for the finished products, which could be related to the quality with influence in the clinical efficacy.…”

“…[10][11][12] But, recently the antifactor IIa (AIIa) which is used for the low molecular weight heparin evaluation, has been suggested as possible harmonized alternative to improve the potency assessment replacing the widely used SPCA. 10,13 Besides the neutralizing properties of protamine sulfate on conventional heparins has been used as safe and effective antidote for controlling excessive bleeding.…”