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1.
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
2.
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
3.
Biochemistry (Mosc) ; 85(Suppl 1): S154-S176, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32087058

RESUMO

In this review, we present the data on the natural occurrence of chitin and its partially or fully deacetylated derivative chitosan, as well as their properties, methods of modification, and potential applications of derivatives with bactericidal, fungicidal, and antioxidant activities. The structure and physicochemical characteristics of the polymers, their functions, and features of chitin microbial synthesis and degradation, including the processes occurring in nature, are described. New data on the hydrolytic microorganisms capable of chitin degradation under extreme conditions are presented. Special attention is focused on the effect of physicochemical characteristics of chitosan, including molecular weight, degree of deacetylation, polydispersity index, and number of amino group derivatives (quaternized, succinyl, etc.) on the antimicrobial and antioxidant properties of modified polymers that can be of particular interest for biotechnology, medicine, and agriculture. Analysis of the available literature data confirms the importance of fundamental research to broaden our knowledge on the occurrence of chitin and chitosan in nature, their role in global biosphere cycles, and prospects of applied research aimed at using chitin, chitosan, and their derivatives in various aspects of human activity.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Quitosana/análogos & derivados , Quitosana/farmacologia , Fungicidas Industriais/farmacologia , Antibacterianos/química , Antibacterianos/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Bactérias/metabolismo , Biotecnologia , Quitosana/química , Quitosana/metabolismo , Proteção de Cultivos , Descoberta de Drogas , Fungicidas Industriais/química , Fungicidas Industriais/economia , Fungicidas Industriais/metabolismo , Humanos , Hidrólise , Peso Molecular , Polímeros
4.
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
5.
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
6.
Prikl Biokhim Mikrobiol ; 52(2): 237-41, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27266254

RESUMO

A number of alkylated (quaternized) and acylated derivatives of low-molecular weight chitosan were obtained. The structure and composition of the compounds were confirmed by the results of IR and PMR spectroscopy, as well as conductometric titration. The effect of the acyl substituent and the degree of substitution of N-(2-hydroxy-3-trimethylammonium) with the propyl fragment appended to amino groups of the C2 atom of polymer chains on antibacterial activity against typical representatives of gram-positive and gram-negative microorganisms (Staphylococcus epidermidis and Escherichia coli) was studied. The highest activity was in the case of N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride with the maximal substitution (98%). The minimal inhibitory concentration of the derivative was 0.48 µg/mL and 3.90 µg/mL for S. epidermis and E. coli, respectively.


Assuntos
Alquilantes/metabolismo , Antibacterianos/metabolismo , Quitosana/metabolismo , Acilação , Alquilantes/farmacologia , Antibacterianos/farmacologia , Quitosana/farmacologia , Escherichia coli/efeitos dos fármacos , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
7.
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
8.
Prikl Biokhim Mikrobiol ; 52(5): 455-9, 2016.
Artigo em Russo | MEDLINE | ID: mdl-29513409

RESUMO

Methods for the determination of residual protein and endotoxins in chitosan preparations, which can be used as vectors for biologically active compounds delivery, are discussed. The limits of their use for the determination of residual impurities in chitosan preparations associated with the structure of the biopolymer are estimated.


Assuntos
Quitosana/análise , Contaminação de Medicamentos , Endotoxinas/análise , Proteínas/análise , Quitosana/química
9.
Prikl Biokhim Mikrobiol ; 52(5): 482-8, 2016.
Artigo em Russo | MEDLINE | ID: mdl-29513413

RESUMO

We obtained a number of conjugates based on a quaternized chitosan derivative and antimicrobial peptides (melittin and warnerin) crosslinked by microbial transglutaminase. We determined the optimal conditions for the synthesis (30 minutes, with a mole ratio of peptides and chitosan derivative of 1.4: 100) and studied the antibacterial properties of obtained conjugates. The antibacterial effect of the conjugates was found to be greater than that of their components. The antibacterial activity of the conjugates was determined by the double-dilution method and by atomic force microscopy.


Assuntos
Antibacterianos/farmacologia , Quitosana , Peptídeos/farmacologia , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica
10.
Prikl Biokhim Mikrobiol ; 51(1): 5-14, 2015.
Artigo em Russo | MEDLINE | ID: mdl-25842898

RESUMO

This review presents an analysis of the literature data over the last decade in order to reveal the relationship between the structure and composition of chitin/chitosan oligomers and their antitumor activity. Oligosaccharides consisting of N-acetylglucosamine and/or glucosamine units connected to each other by ß-1,4-O-glycoside bond are generally called chitooligosaccharides. Homochitooligosaccharides are the oligomers of N-acetylglucosamine (AGA) or glucosamine (GA). Heterooligosaccharides are a mixture of various oligomers differing in the degree of polymerization (DP), acetylation (DA), or deacetylation (DD), as well as in the location of N-acetyl residues in the oligomer chain. Heterochitooligomers with a polymerization degree of no more than 10 are usually water soluble. The solubility of chitooligosaccharides with a DP of more than 10 depends on the DA and pH of a solution. The pharmaceutical and food industries, as well as scientists engaged in basic research, are interested in the use of heterochitooligosaccharides. This is explained by their unique properties, such as good water solubility; minimal toxicity; biocompatibility; the ability to penetrate cell membranes, resulting in a high degree of absorption (unlike chitin and chitosan); and their biological activity. Therefore, in the last decade, researchers have focused their attention on studying the relationship of the structure of oligosaccharides and their specific activity, such as antitumor, antimicrobial, antioxidant, immunemodulatory, and other activities. This is shown by the number of publications, which has doubled compared to the number in 2001.


Assuntos
Quitina/uso terapêutico , Quitosana/uso terapêutico , Neoplasias/tratamento farmacológico , Oligossacarídeos/uso terapêutico , Antioxidantes/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Quitina/síntese química , Quitina/química , Quitosana/síntese química , Quitosana/química , Humanos , Imunização , Neoplasias/patologia , Oligossacarídeos/síntese química , Oligossacarídeos/química , Água/química
11.
Prikl Biokhim Mikrobiol ; 50(4): 422-8, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25707119

RESUMO

Samples of low-molecular weight chitosan with molecular masses of 8-24 kDa, identical deacetylation degrees (85%), and polydispersity indexes soluble at pH 5-7 were obtained by enzymatic hydrolysis using an enzyme complex from the micelial fungi Myceliophthora fergusii with yields of 50-80%. The optimal conditions for hydrolysis were found (pH 5.6, 37 degrees C, an enzyme/substrate ratio 1/800, 15-60 min). The obtainment of chitosan sample sets with different characteristics will enable the selection of the most efficient ones for comparison in in vitro/in vivo experiments.


Assuntos
Quitinases/química , Quitosana/química , Proteínas Fúngicas/química , Micélio/química , Saccharomycetales/química , Quitinases/metabolismo , Liofilização , Proteínas Fúngicas/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Peso Molecular , Micélio/enzimologia , Saccharomycetales/enzimologia , Temperatura
12.
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
13.
Prikl Biokhim Mikrobiol ; 47(6): 699-706, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22288200

RESUMO

The influence of neutral and ionic polysaccharides on the antioxidant (AOA) and detoxifying activities of lactoferrin (LF) and the duration of its circulation in the body was studied. In addition to natural polymers, we studied artificial chitosan derivatives with different functional groups. On the basis ofAOA test, five polysaccharides were selected. The study of the detoxifying effect of LF in two models of induced toxicity revealed polysaccharides that maintained or increased the detoxifying activity of LF. We established that the formation of a complex of lactoferrin with two galactomannans and succinyl chitosan caused positive changes in LF properties: the detoxifying activity of the protein remained unchanged or increased, whereas its elimination from the body was decelerated.


Assuntos
Antioxidantes/farmacocinética , Quitosana/administração & dosagem , Lactoferrina/farmacocinética , Falência Hepática Aguda/tratamento farmacológico , Fígado/efeitos dos fármacos , Mananas/administração & dosagem , Animais , Antioxidantes/uso terapêutico , Varredura Diferencial de Calorimetria , Tetracloreto de Carbono/toxicidade , Cisplatino/toxicidade , Dextranos/administração & dosagem , Sinergismo Farmacológico , Galactanos/administração & dosagem , Galactose/análogos & derivados , Humanos , Lactoferrina/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Camundongos , Camundongos Endogâmicos
14.
Izv Akad Nauk Ser Biol ; (4): 403-10, 2010.
Artigo em Russo | MEDLINE | ID: mdl-20799640

RESUMO

Comparative study of chitosan wound healing properties and its synthesized derivatives in MC-100 gel was carried out using the model of experimental full thickness skin wounds. It was determined that N-sulfosuccinoyl chitosan derivatives added into the gel in a concentration of 0.05% possess the higher wound healing activity in comparison with other chitosan derivatives and decrease the half-healing period of wounds 2-3 times in comparison with the control.


Assuntos
Quitosana/análogos & derivados , Quitosana/farmacologia , Pele/efeitos dos fármacos , Succinatos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Géis , Camundongos , Pele/lesões , Relação Estrutura-Atividade
15.
Prikl Biokhim Mikrobiol ; 46(3): 379-84, 2010.
Artigo em Russo | MEDLINE | ID: mdl-20586293

RESUMO

A study of biological activity of the derivatives of the chitin-chitosan oligomer with salicylic acid and its fragments showed that chitosan salicylate actively protected potato tubers against Phytophthora infestans but sharply inhibited reparation of potato tissues. N-(2-Hydroxybenzyl)chitosan exhibited good protective properties but did not influence wound reparation. N-(2-Hydroxy-3-methoxybenzyl)-N-pyridox-chitosan, which contained the pyridoxal and 2-hydroxy-3-methoxy fragments, was the most efficient, stimulating both defense against late blight and wound reparation in potato tissues.


Assuntos
Quitosana/farmacologia , Phytophthora infestans/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Tubérculos/microbiologia , Salicilatos/farmacologia , Solanum tuberosum/microbiologia , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/química , Fatores Imunológicos/síntese química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Phytophthora infestans/imunologia , Doenças das Plantas/imunologia , Tubérculos/imunologia , Salicilatos/síntese química , Salicilatos/química , Solanum tuberosum/imunologia
17.
Prikl Biokhim Mikrobiol ; 45(4): 415-21, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19764609

RESUMO

This article describes the optimal conditions for the enzymatic hydrolysis of chitosan and its chemically-modified derivatives using the preparation extracted from the king crab hepatopancrease possessing pronounced hydrolythic activity. The following preparations were used: chitosan with a molecular weight of 100 kDa and an acetylation level of 0.15, carboxymethyl chitosan 200 kDa witih an extent of replacement of 0.23, and N-succinyl chitosan 390 kDa with an extent of replacement of 0.8. Low molecular-weight samples of chitosan and of its modified derivatives were obtained with the yields of 85, 55, and 80%, respectively. The conditions of the hydrolysis were as follows: an enzyme: substrate ratio of 1:200, 37 degrees C, and 20 h duration of hydrolysis.


Assuntos
Anomuros/química , Quitosana/química , Quitosana/isolamento & purificação , Animais , Anomuros/enzimologia , Quitosana/análogos & derivados , Hepatopâncreas/química , Hepatopâncreas/enzimologia , Hidrólise , Peso Molecular
18.
Eksp Klin Gastroenterol ; (5): 42-6, 2009.
Artigo em Russo | MEDLINE | ID: mdl-20205328

RESUMO

Digestive/absorptive function of small intestine was determined using loading tests in postcholecystectomy patients. Disturbances of both uptaking/excretory liver function and biochemical composition of hepatic bile in patients with early and late terms after cholecystectomy were studied. Interactions between the disturbances in hepatobiliary system and the small intestine as well as their influence on the pathogenesis of PCES were estimated.


Assuntos
Bile/metabolismo , Colecistectomia , Absorção Intestinal , Enteropatias , Fígado/metabolismo , Fígado/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Enteropatias/metabolismo , Enteropatias/patologia , Enteropatias/fisiopatologia , Masculino , Síndrome
19.
Patol Fiziol Eksp Ter ; (3): 20-3, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18946908

RESUMO

We studied anticoagulant activity in vitro and in vivo of sulfate depolymerisation galactomannan guar with the following characteristics: Man:Gal 1.64, molecular mass 127 kDa, sulfation degree 1.46. We found the ability of galactomannan-HSO3Na (GM) to increase the time of blood coagulation in the test aPTT with an increase of its concentration and to decrease velocity of chromogenic substrate on the factor Xa hydrolysis. Specific antithrombin and anti-factor Xa activities of GM were 35.8 +/- 1.8 IU/mg and 6.6 +/- 0.5 IU/mg, respectively. In biospecific electrophoresis complexes arise between GM and protamine sulfate. Intravenous injection of GM to rats prolonged plasma coagulation time in the aPTT test with dose reduction from 1 to 3 mg/kg. In rat thrombosis model a dose of 3 Mg/kg produced a 100% inhibition of blood clot.


Assuntos
Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Fator Xa/metabolismo , Mananas/farmacologia , Trombose/tratamento farmacológico , Animais , Modelos Animais de Doenças , Galactose/análogos & derivados , Hidrólise , Masculino , Ratos , Ratos Wistar , Trombose/metabolismo
20.
Prikl Biokhim Mikrobiol ; 44(5): 606-14, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18822784

RESUMO

The possibility of obtaining monosaccharide derivatives of low-molecular-weight chitosan with the use of the Maillard reaction was studied. Chitosan derivatives (molecular weight, 24 and 5 kDa) obtained with glucosamine, N-acetyl galactosamine, galactose, and mannose with a substitution degree of 4-14% and a yield of 60-80% were obtained. Some physicochemical and biological properties of these derivatives were studied. We showed that monosaccharide derivatives of low-molecular-weight chitosan exhibited antibacterial activity. Chitosan at a concentration of 0.01% caused 100% death of bacteria B. subtilis and E. coil. The strongest antibacterial effect was exhibited by 24-kDa derivatives: only 0.02-0.08% of cells survived. These derivatives were two orders of magnitude more effective than the 5-kDa chitosan modified with galactose.


Assuntos
Antibacterianos/química , Antibacterianos/isolamento & purificação , Quitosana/química , Hexoses/química , Hexoses/isolamento & purificação , Antibacterianos/farmacologia , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/crescimento & desenvolvimento , Hexoses/farmacologia , Peso Molecular
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