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1.
Bull Exp Biol Med ; 177(5): 621-625, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39347869

RESUMO

The hemocompatibility of arabinogalactan, betulin and its derivatives was evaluated in vitro and samples suitable for creation of nanostructures or materials in contact with blood were selected. The prospects of arabinogalactan as a component of the construct (nanostructure) for drug delivery are due to the fact that it did not affect blood/plasma coagulation (at concentrations of 0.0033-3.333 mg/ml and 0.00465-4.65 mg/ml, respectively), platelet aggregation (0.00182-0.182 mg/ml), and demonstrated the degree of erythrocyte hemolysis less than 3%. Sodium salt of betulin monosulfate, diarginine salt of betulin disulfate (up to 0.465 mg/ml), and especially betulin and allobetulin formate with procoagulant properties (degree of hemolysis less than 2%) can be used to create a material, for example, sponge, gel, active against blood coagulation.


Assuntos
Coagulação Sanguínea , Galactanos , Hemólise , Agregação Plaquetária , Triterpenos , Triterpenos/química , Triterpenos/farmacologia , Hemólise/efeitos dos fármacos , Galactanos/química , Galactanos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Teste de Materiais , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Eritrócitos/efeitos dos fármacos , Animais , Ácido Betulínico
2.
Bull Exp Biol Med ; 176(2): 227-231, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38194064

RESUMO

Intravenous injection of cationic starch conjugated with sterically hindered phenol (terpenophenol) to guinea pigs did not increase hemorrhagic activity (in doses of 2 and 4 mg/kg) and plasma clotting time in activated partial thromboplastin time and prothrombin time tests (in a dose of 4 mg/kg) in comparison with administration of physiological saline. Intravenous injection of the cationic starch conjugate with the highest content of terpenophenol fragments (4.1%wt) in a dose of 2 mg/kg to guinea pigs leads to a decrease in hemorrhagic activity by 4 times in comparison with the control.


Assuntos
Hemorragia , Fenol , Cobaias , Animais , Tempo de Protrombina , Tempo de Tromboplastina Parcial , Injeções Intravenosas
3.
Bull Exp Biol Med ; 173(1): 98-104, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35622245

RESUMO

We identified compounds that do not independently provoke aggregation of human platelets and do not affect hemolysis of human erythrocytes in vitro: lacking anticoagulant activity sulfated galactoglucomannan (polydispersity 1.43; degree of sulfation 0.66) in concentrations ≤0.2 mg/ml; exhibiting anticoagulant activity (in concentrations up to 0.002 mg/ml) sulfated galactoglucomannan (polydispersity 1.5; degree of sulfation 1.81) and galactomannan obtained by sulfation with the sulfamic acid-urea complex (polydispersity 2.75; degree of sulfation 1.25) and galactomannans obtained by sulfation with chlorosulfonic acid in 1,4-dioxane (polydispersity 1.61/22.27; degree of sulfation 1.00/0.74).


Assuntos
Mananas , Sulfatos , Anticoagulantes/farmacologia , Galactose/análogos & derivados , Humanos , Mananas/farmacologia , Sulfatos/farmacologia
4.
Bull Exp Biol Med ; 172(1): 33-37, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34792720

RESUMO

Oligochitosan Сh10/85 with a molecular weight of 10 kDa and a deacetylation degree of 85% prevented the development of experimental venous thrombosis in guinea pigs after intravenous administration in a dose of 30 mg/kg. In a concentration of 0.005-0.5 mg/ml, oligochitosan Ch10/85 did not provoke hemolysis of human red blood cells in in vitro experiments. The antithrombotic effect of oligochitosan Ch10/85 that exhibits low anticoagulant activity (by two orders of magnitude lower than that of unfractionated heparin) can be associated with inhibition of platelet aggregation.


Assuntos
Anticoagulantes/uso terapêutico , Quitosana/uso terapêutico , Oligossacarídeos/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/prevenção & controle , Animais , Clorófitas/química , Eritrócitos/efeitos dos fármacos , Feminino , Cobaias , Humanos
5.
Bull Exp Biol Med ; 169(6): 815-820, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123918

RESUMO

The effects of sulfated organosolv lignins derived from fir (Abies sibirica) and larch (Larix sibirica) (SLf and SLl; 4-3-7.5% sulfur, median-weight molecular mass 2960-4888 Da), on human blood/plasma clotting, platelet aggregation, and erythrocyte hemolysis were studied in vitro. Antithrombin activities of the samples were below 2 U/mg. Specimens of SLf (sulfur content 6.5, 6.6, and 7.5%, molecular weights 3503, 3487, and 3580 Da, respectively) and SLl (4.3 and 6.3%, 2960 and 3497 Da) in a concentration of 0.01 mg/ml did not prolong the blood clotting time, did not provoke human platelet aggregation, did not destroy erythrocyte membranes, and could be used for construction of drug delivery systems. The SLf sample (6.5%, sulfur, 3503 Da) in concentrations from 0.09 to 1.82 mg/ml did not stimulate platelet aggregation, reduced ADP-induced platelet aggregation, and 2-fold prolonged the blood/plasma clotting time 2-fold in comparison with control and could be used for creation of biomaterial with clot-resistant surface.


Assuntos
Abies/química , Materiais Biocompatíveis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Larix/química , Lignina/farmacologia , Difosfato de Adenosina/farmacologia , Antitrombinas/análise , Materiais Biocompatíveis/química , Materiais Biocompatíveis/isolamento & purificação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Células Cultivadas , Sistemas de Liberação de Medicamentos/métodos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Lignina/química , Lignina/isolamento & purificação , Teste de Materiais , Peso Molecular , Agregação Plaquetária/efeitos dos fármacos , Sulfatos/química , Madeira/química
6.
Bull Exp Biol Med ; 168(4): 507-511, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32147767

RESUMO

We studied hemocompatibility of silver nanoparticles synthesized on the basis of a conjugate of quaternized chitosan with gallic acid (QChit-Gal). For the three variants of silver particles (Nos. 1, 2, and 3), the QChit-Gal:AgNO3 ratio was 5:1, 5:3, and 1:1, respectively. Anticoagulant activity of all samples of silver nanoparticles was lower than that of the conjugate. Samples of nanoparticles Nos. 1 and 2 in a concentration of 0.0233 mg/ml did not affect plasma clotting time and can be used for intravenous administration. However, their concentration in the blood should not exceed 0.01 mg/ml, because in this concentration they do not affect erythrocyte membrane, do not induce platelet aggregation, and do not affect platelet aggregation induced by ADP.


Assuntos
Quitosana/química , Eritrócitos/efeitos dos fármacos , Ácido Gálico/química , Glicoconjugados/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Trifosfato de Adenosina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Eritrócitos/citologia , Glicoconjugados/química , Hemólise/efeitos dos fármacos , Humanos , Agregação Plaquetária/efeitos dos fármacos , Cultura Primária de Células , Prata/química
7.
Bull Exp Biol Med ; 167(2): 279-283, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31243674

RESUMO

Quaternized derivatives of chitosan with a substitution degree of 85-98% (highly substituted) synthesized from chitosans with a molecular weight of 5, 10, 20 kDa, with a degree of deacetylation of 89-98%, and the code numbers of QChit 5, QChit 10, QChit 20, respectively, completely neutralize antithrombin activity of unfractionated heparin and partially neutralize aXa activity of low-molecular-weight heparin (clexane), similar to protamine sulfate. The advantages of QChit 5 and QChit 10 over QChit 20 and protamine sulphate are the follows: the effect is achieved at lower concentrations and in greater concentration range; they do not promote platelet aggregation; in a concentration of 0.0072 mg/ml they do not destroy the erythrocyte membranes.


Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Quitosana/química , Heparina/química , Heparina/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Testes de Coagulação Sanguínea , Hemólise/efeitos dos fármacos , Humanos
8.
Bull Exp Biol Med ; 164(6): 766-769, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29658080

RESUMO

Nanocrystalline particles of chitin in the form of hydrosol in a concentration of 0.63 mg/ml have no effect on aggregation of human platelets and clotting time of platelet-poor plasma in coagulation tests. ADP-induced aggregation of human platelets was inhibited by these nanoparticles in concentrations of 0.63 and 1.00 mg/ml in comparison with the control. Intravenous administration of nanoparticles in a dose of 1 mg/kg to guinea pigs produced no anticoagulant effect. The nanocrystalline particles of chitin can be of interest as potential drug delivery systems.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Quitina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Difosfato de Adenosina/farmacologia , Exoesqueleto/química , Animais , Testes de Coagulação Sanguínea , Plaquetas/efeitos dos fármacos , Braquiúros , Quitina/química , Quitina/isolamento & purificação , Cristalização , Feminino , Cobaias , Humanos , Injeções Intravenosas , Nanopartículas/ultraestrutura , Agregação Plaquetária/efeitos dos fármacos
9.
Bull Exp Biol Med ; 163(3): 340-343, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28744652

RESUMO

Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 70 aIIa U/kg non-fractionated heparin shortened plasma clotting time (shown by partial activated thromboplastin time, thrombin time, and prothrombin time). Intravenous injection of protamine sulfate or quarternized chitosan derivative to guinea pigs after injection of 1 mg/kg (100 aXa U/kg) low-molecular-weight heparin (clexane) led to shortening of plasma clotting time in the ReaClot Heparin test and to prolongation of plasma amidolytic activity in the factor Xa chromogenic substrate test.


Assuntos
Anticoagulantes/farmacocinética , Antídotos/farmacocinética , Quitosana/farmacocinética , Heparina de Baixo Peso Molecular/farmacocinética , Heparina/farmacocinética , Compostos de Amônio Quaternário/farmacocinética , Animais , Anticoagulantes/farmacologia , Antídotos/síntese química , Antídotos/farmacologia , Quitosana/síntese química , Quitosana/farmacologia , Feminino , Cobaias , Heparina/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Injeções Intravenosas , Tempo de Tromboplastina Parcial , Protaminas/síntese química , Protaminas/farmacocinética , Protaminas/farmacologia , Tempo de Protrombina , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/farmacologia , Tempo de Trombina
10.
Bull Exp Biol Med ; 162(4): 462-465, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28243911

RESUMO

Sulfation (to 2.8) of dextrans with molecular weight of 150 and 20 kDa was followed by the appearance of anticoagulant activity that increased with decreasing their molecular weight and did not depend on antithrombin, plasma inhibitor of serine proteases of the blood coagulation system. Antithrombin activity of dextran sulfate with a molecular weight of 20 kDa reached 12.6-15.3 U/mg. Dextran sulfates with molecular weights of 20 and 150 kDa did not potentiate ADP-induced human platelet aggregation.


Assuntos
Anticoagulantes/química , Coagulação Sanguínea/efeitos dos fármacos , Sulfato de Dextrana/farmacologia , Dextranos/química , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Anticoagulantes/farmacologia , Antitrombina III/antagonistas & inibidores , Antitrombina III/metabolismo , Testes de Coagulação Sanguínea , Plaquetas/efeitos dos fármacos , Dextranos/farmacologia , Heparina/farmacologia , Humanos , Peso Molecular , Relação Estrutura-Atividade
11.
Bull Exp Biol Med ; 164(2): 158-161, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29185171

RESUMO

Sulfated derivatives of xylan (isolated from Bétula pubéscens wood) with average molecular weight ~34 kDa, sulfur content of 11.3-17.5%, a degree of substitution of 0.74-1.64 are anticoagulants of direct type of action. Antithrombin and antifactor Xa activities in three tested xylan samples did not differ and reached 30.8-31.8 and 13.5-14.3 U/mg, respectively.


Assuntos
Anticoagulantes/farmacologia , Fator Xa/metabolismo , Trombina/antagonistas & inibidores , Xilanos/farmacologia , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Betula/química , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Humanos , Peso Molecular , Extratos Vegetais/química , Sulfatos/química , Trombina/metabolismo , Xilanos/química , Xilanos/isolamento & purificação
12.
Bull Exp Biol Med ; 160(6): 767-70, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27165079

RESUMO

Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration.


Assuntos
Anticoagulantes/administração & dosagem , Celulose/análogos & derivados , Administração Intravenosa , Animais , Coagulação Sanguínea/efeitos dos fármacos , Celulose/administração & dosagem , Relação Dose-Resposta a Droga , Fator Xa/metabolismo , Heparina/farmacologia , Coelhos
13.
Prikl Biokhim Mikrobiol ; 52(4): 421-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29512988

RESUMO

Alkylated derivatives of low molecular weight chitosan with different substitution degrees of 98, 40, and 9% (I, II, and III respectively) have been synthesized. The structure of the obtained derivatives was defined by spectral assays (IR-spectroscopy and proton magnetic resonance). Chitosan derivatives were characterized with positive zeta-potential (33­51 mV) and solubility from 2 to 100 mg/mL in pH 7.4 and 25°C. It was shown that, at a concentration of 0.0014­0.0029 mg/mL, derivative I, as well as protamine sulfate, could be used to neutralize the anticoagulant activity of unfractionated or low molecular weight heparin. At a concentration of 0.0029­0.58 mg/mL, derivative I enhanced platelet aggregation, which would be necessary when hemostatic compounds or materials were used. Derivatives II and III enhanced platelet aggregation to a lesser extent.


Assuntos
Anticoagulantes , Plaquetas/metabolismo , Quitosana , Antagonistas de Heparina , Heparina , Agregação Plaquetária/efeitos dos fármacos , Anticoagulantes/química , Anticoagulantes/farmacologia , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Heparina/química , Heparina/farmacologia , Antagonistas de Heparina/química , Antagonistas de Heparina/farmacologia , Humanos
14.
Bull Exp Biol Med ; 156(1): 44-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24319726

RESUMO

RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human, rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36 is lower than that of recombinant hirudin. During inhibition of human plasma clotting activated with echitox (coagulase from Echis multisquamatus venom), the aptamer presumably binds to meisothrombin exosite I. The sensitivity of human plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36 binding to coagulase of Agkistrodon halys venom (ancistron) is required for proving the effect of aptamer on polymerization of human fibrinogen.


Assuntos
Anticoagulantes/farmacologia , Aptâmeros de Nucleotídeos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Coagulase/farmacologia , Proteínas de Répteis/farmacologia , Trombina/fisiologia , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Coelhos , Ratos , Venenos de Víboras/enzimologia
15.
Eksp Klin Farmakol ; 76(10): 20-4, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24400384

RESUMO

Polyanions (in an amount within 1.5 - 6.0 mg), including cellulose sulfates (excreted from Gossipium hirsutum L., molecular weight 22.0 kDa, degree of sulfation within 0.8 - 1.8), inulin sulfates (excreted from Helianthus tuberosus, molecular weight 8.0 kDa, degree of sulfation within 0.6 - 1.6), pectin sulfates (excreted from Abies sibirica L., molecular weight 24.0 kDa, degree of sulfation within 0.8 - 1.1), give rise to peaks of precipitation with polycations of protamine sulfate. Only cellulose sulfates (in amount within 0.38 - 6.00 mg) give the peaks of precipitation with chitosan polycations (molecular weight 10 kDa, degree of deacetylation 85%) during horizontal biospecific electrophoresis. The height of the peak of precipitation with protamin sulfate was found to grow with increasing antithrombin activity of cellulose sulfates and pectin sulfate (for polyanions in an amount within 1.5 - 6 mg). The size of the area of precipitation with chitosan was found to decrease with increasing antithrombin activity of cellulose sulfates.


Assuntos
Anticoagulantes/química , Celulose/análogos & derivados , Sulfatos de Condroitina/química , Inulina/química , Pectinas/química , Poliaminas/química , Protaminas/química , Anticoagulantes/isolamento & purificação , Coagulação Sanguínea , Celulose/química , Celulose/isolamento & purificação , Sulfatos de Condroitina/isolamento & purificação , Eletroforese em Gel de Ágar/métodos , Gossypium/química , Humanos , Inulina/análogos & derivados , Inulina/isolamento & purificação , Peso Molecular , Pectinas/isolamento & purificação , Pinus/química , Poliaminas/isolamento & purificação , Polieletrólitos , Trombina/química
16.
Int J Biol Macromol ; 253(Pt 8): 127608, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37879584

RESUMO

Uncontrolled bleeding that occurs during surgery, trauma, and in combat conditions is critical and require immediate action. Chitosan is a polysaccharide, obtained from natural sources with unique biological properties. It is often used as basis for local hemostatic agents (LHA). We summarized the data on hemostatic properties of chitosan, commercially available chitosan-based products with focus in the field of chemical modification of chitosan. Various approaches are used to enhance hemostatic activity of chitosan-based materials. The approach with chemical modification of chitosan allows changing the properties of the polymer in order to obtain an active macromolecule that contributes to hemostasis. Ongoing research on the mechanism of interaction with blood components in the case of different chitosan derivatives will make it possible to identify promising directions for chemical modification to obtain an effective LHA.


Assuntos
Quitosana , Hemostáticos , Humanos , Hemostáticos/farmacologia , Hemostáticos/química , Quitosana/farmacologia , Quitosana/química , Hemostasia , Hemorragia/tratamento farmacológico , Polímeros/farmacologia
17.
Eksp Klin Farmakol ; 75(6): 31-5, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22891439

RESUMO

We have studied a relationship between the degree of sulfonation and anticoagulant activity of starch from Solanum tuberosum (molecular weight, 25000-30000 Da; sulfonation degree, 0.4-2.5) and inulin from Helianthus tuberosus (molecular weight, 7000-8000 Da; sulfonation degree, 0.6-1.6). Starch and inulin sulfates (i) increased the time of appearance of fibrin clots in plasma in coagulometric tests and (ii) reduced (via antithrombin) the rate of thrombin-induced hydrolysis of a chromogen substrate. The antithrombin (aIIa) activity of starch sulfates reached 16.8-70.0 IU/mg and the activity against factor Xa (aXa activity) was 2.3-16.6 IU/mg. The antithrombin activity of inulin sulfates was within 5.5-11.4 IU/mg and the activity against factor Xa (aXa activity) was within 0-1.4 IU/mg. An increase in the degree of sulfonation led to a growth in the anticoagulant activity of starch sulfates. The anticoagulant activity of starch sulfates and inulin sulfate with sulfonation degree 1.0 is mediated by antithrombin, which is the plasma inhibitor of serine proteases.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fibrina/antagonistas & inibidores , Inulina/farmacologia , Amido/farmacologia , Compostos de Enxofre/farmacologia , Antitrombina III/antagonistas & inibidores , Inibidores do Fator Xa , Fibrina/biossíntese , Helianthus/química , Humanos , Inulina/análogos & derivados , Peso Molecular , Solanum tuberosum/química , Amido/análogos & derivados , Relação Estrutura-Atividade , Trombina/antagonistas & inibidores
18.
Eksp Klin Farmakol ; 75(11): 13-8, 2012.
Artigo em Russo | MEDLINE | ID: mdl-23323327

RESUMO

DNA aptamer RA36 with a molecular weight of 10000 is direct-acting anticoagulant whose efficacy is lower than that of recombinant hirudin and unfractionated heparin (UFH) in blood clotting time (BCT), activated blood recalcification time (ABRT), recalcification time (RT), prothrombin time (PT), and activated partial thromboplastin time (APTT) tests. The anticoagulant effect of RA36 is comparable with that of UFH in the thrombin time (TT) test, but is lower than the effect of recombinant hirudin. Analysis of the blood and plasma anticoagulant activity during intravenous bolus administration of aptamer RA36 in rabbits and rats is based on the use ABRT (in blood case) and APTT/RT (in plasma case) tests. The range of doses for evaluation of pharmacodynamic parameters of RA36 during intravenous bolus administration in rabbits and rats is 3 - 34 mg/kg and 1 - 27 mg/kg, respectively. Accordingly, designed dose range for humans is 1 -29 mg/kg.


Assuntos
Anticoagulantes/farmacologia , Aptâmeros de Nucleotídeos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Animais , Anticoagulantes/síntese química , Anticoagulantes/farmacocinética , Aptâmeros de Nucleotídeos/síntese química , Aptâmeros de Nucleotídeos/farmacocinética , Cálculos da Dosagem de Medicamento , Heparina/farmacocinética , Heparina/farmacologia , Hirudinas/farmacocinética , Hirudinas/farmacologia , Humanos , Injeções Intravenosas , Masculino , Peso Molecular , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Coelhos , Ratos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia
20.
Bull Exp Biol Med ; 152(1): 61-5, 2011 Nov.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-22803041

RESUMO

Sulfated derivatives based on powdered cellulose were obtained, including those containing additional (carboxymethyl, ethyl amide or phosphate) groups, and their activity against blood clotting factors (thrombin and Xa) was studied. Maximum antithrombin activity of the test compounds, measured using a coagulation test, was 144±11 U/mg.


Assuntos
Antitrombinas/farmacologia , Celulose/análogos & derivados , Celulose/farmacologia , Sulfatos/farmacologia , Antitrombinas/química , Celulose/química , Fator Xa , Humanos , Peso Molecular , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Sulfatos/química , Trombina , Tempo de Trombina
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