clinmedКлиническая медицинаClinical Medicine (Russian Journal)0023-21492412-1339ООО «Медицинское информационное агентство»10.30629/0023-2149-2024-102-8-602-609clinmed-925Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESИспользование хитозана различного происхождения в медицинеUse of chitosan of various origins in medicinehttps://orcid.org/0000-0002-3446-5362КоптеваЛ. А.KoptevaL. A.

Коптева Любовь Андреевна — врач-ординатор-онколог 

Тула

Lyubov A. Kopteva — resident oncologist 

Tula 

koptevatula@gmail.comhttps://orcid.org/0000-0003-0566-1476ОбъедковЕ. Г.ObiedkovE. G.

Объедков Евгений Геннадьевич — канд. мед. наук, ассистент кафедры хирургических болезней №1

Курск

Evgeny G. Obiedkov — Candidate of Medical Sciences, Assistant of the Department of Surgical Diseases No. 1

Kursk

https://orcid.org/0000-0003-3835-0594МишинаЕ. С.MishinaE. S.

Мишина Екатерина Сергеевна — канд. мед. наук, зав. лабораторией морфологии и клеточных технологий НИИ Экспериментальной медицины, доцент кафедры гистологии, эмбриологии, цитологии 

Курск

Ekaterina S. Mishina — Candidate of Medical Sciences, Head of the Laboratory of Morphology and Cell Technologies of the Research Institute of Experimental Medicine, Associate Professor of the Department of Histology, Embryology, Cytology 

Kursk 

https://orcid.org/0000-0001-7540-5748ИвановИ. С.IvanovI. S.

Иванов Илья Сергеевич — д-р мед. наук, профессор, зав. кафедрой хирургических болезней №1 

Курск

Ilya S. Ivanov — Doctor of Medical Sciences, Professor, Head of the Department of Surgical Diseases No. 1 

Kursk 

https://orcid.org/0009-0006-7408-5985ТерентьевА. К.TerentyevA. K.

Терентьев Андрей Константинович — врач-стоматолог-хирург, лечебно-профилактическое отделение №7 

Тула

Andrey K. Terentyev — dentist-surgeon , medical and preventive department No. 7

Tula

https://orcid.org/0000-0003-2072-5511ОбъедковаН. Ю.ObiedkovaN. Yu.

Объедкова Наталья Юрьевна — ассистент кафедры поликлинической терапии и общей врачебной практики 

Курск

Natalia Y. Obiedkova — Assistant of the Department of Polyclinic Therapy and General Medical Practice 

Kursk

ФГБОУ ВО «Тульский государственный университет» Медицинский институтРоссияTula State University Medical InstituteRussian FederationФГБОУ ВО «Курский государственный медицинский университет» Минздрава РоссииРоссияKursk State Medical UniversityRussian FederationГБУЗ «Тульская областная стоматологическая поликлиника»РоссияTula Regional Dental PolyclinicRussian Federation2024110120251028602609Copyright © Коптева Л.А., Объедков Е.Г., Мишина Е.С., Иванов И.С., Терентьев А.К., Объедкова Н.Ю., 20252025Коптева Л.А., Объедков Е.Г., Мишина Е.С., Иванов И.С., Терентьев А.К., Объедкова Н.Ю.Kopteva L.A., Obiedkov E.G., Mishina E.S., Ivanov I.S., Terentyev A.K., Obiedkova N.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.clinmedjournal.com/jour/article/view/925

Хитозан широко используется во всех сферах деятельности человека. Его получают из животных, насекомых и растений, в составе которых есть хитин, за счет химической очистки последнего. Наиболее востребовано сырье животного происхождения, а наиболее перспективно — из насекомых. Основные положения. Хитозан широко применяется в медицине: в нутрициологии, хирургии, гематологии, стоматологии и онкологии. Он обладает биосовместимостью, биорезорбируемостью, нетоксичностью, гемостатичностью, пластичностью, адгезивностью, имеетантибактериальные свойства. За счет возможности изменять химическую формулу хитозана, его молекулярнуюмассу и заряд, комбинировать его с различными веществами можно найти новые области применения этого вещества, более дешевые пути его добычи. Детоксикационные, сорбционные, гиполипидемические свойства хитозана востребованы в нутрициологии и гастроэнтерологии. Влияние хитозана на различные фазы регенерации, антикоагулянтные свойства используются в хирургии. Остеоиндуктивные эффекты соединений хитозана применяются в стоматологии и травматологии. Гемостатические и антибактериальные, противопухолевые и радиопротективные свойства хитозана являются основными научными направлениями в неотложной хирургии и онкологии соответственно. Заключение. Широкое применение хитозана во всех сферах деятельности человека, особенно в медицине, делает его востребованным и перспективным веществом. Для того, чтобы расширить производство различных веществ на основе хитозана, необходимо найти новые более дешевые средства для получения хитозана из хитина, наладить маршрутизацию от начального сырья до конечного вещества, разработать российские независимые аналоги лекарственных форм хитозана.

Chitosan is widely used in all areas of human activity. It is obtained from animals, insects, and plants containing chitin through chemical purification. Animal-derived raw materials are most in demand, while insect-derived sources are the most promising. Main Provisions. Chitosan is extensively used in medicine: in nutrition, surgery, hematology, dentistry, and oncology. It exhibits biocompatibility, bioresorbability, non-toxicity, hemostatic properties, plasticity, adhesive qualities, and has antibacterial properties. By altering the chemical formula of chitosan, its molecular weight and charge, and combining it with various substances, new application areas and more economical extraction methods can be found. Detoxifying, sorptive, and hypolipidemic properties are sought after in nutrition and gastroenterology. The effects of chitosan on various phases of regeneration, as well as its anticoagulant properties, are utilized in surgery. Chitosan’s osteoinductive efects are applied in dentistry and traumatology, while its hemostatic, antibacterial, antitumor, and radioprotective properties are key research directions in emergency surgery and oncology, respectively. Conclusion. The widespread application of chitosan in all areas of human activity, especially in medicine, makes it a sought-after and promising substance. To expand the production of various chitosan-based substances, it is essential to find new, cheaper methods for extracting chitosan from chitin, streamline the routes from raw materials to final products, and develop independent Russian equivalents of chitosan drug forms.

хитозанхитинхирургияонкологиястоматологияchitosanchitinsurgeryoncologydentistryReferencesПетрович Ю.А., Григорьянц Л.А., Гурин А.Н., Гурин Н.А. Хитозан: структура и свойства. Использование в медицине. Стоматология. 2008;87(4):72–78.Petrovich Yu.A., Grigor’yants L.A., Gurin A.N., Gurin N.A. Chitosan: structure and properties. Use in medicine. Stomatologiya. 2008;87(4):72–78. (In Russian)].Быкова В., Немцов В.С. Сырьевые источники и способы получения хитина и хитозана. Хитин и хитозан. Получение, свойства и применение. Под ред. К.Г. Скрябина, Г.А. Вихревой, В.П. Варламова. Москва. Изд. «Наука», 2006;7–23.Bykova V., Nemtsov V.S. Raw sources and methods of obtaining chitin and chitosan. Chitin and chitosan. Receipt, properties and application. Edited by K.G. Scriabin, G.A. Vikhreva, V.P. Varlamov. Moscow. Publishing house «Nauka». 2006;7–23. (In Russian)].RodwellMurray R.K., Granner D.K., Mayes P.A., Victor W. Harper’s Biochemistry 25th ed. Stamford, 2000;927.RodwellMurray R.K., Granner D.K., Mayes P.A., Victor W. Harper’s Biochemistry 25th ed. Stamford, 2000;927.Grishin A.A., Zorina N.V., Lutsky V.I. Chitin and chitozan: chemistry, biological activity, application. University Bulletin. Applied Chemistry and Biotechnology. Irkutsk. 2014;7(1):29–34.Grishin A.A., Zorina N.V., Lutsky V.I. Chitin and chitozan: chemistry, biological activity, application. University Bulletin. Applied Chemistry and Biotechnology. Irkutsk. 2014;7(1):29–34.Mukatova M.D., Kirichko N.A., Romanenkova E.N. Qualitative characteristics of chitin and chitosan obtained from the shell of waste containing crayfish waste. Vestnik MGTU. Murmansk, 2015;18(4):641–646.Mukatova M.D., Kirichko N.A., Romanenkova E.N. Qualitative characteristics of chitin and chitosan obtained from the shell of waste containing crayfi sh waste. Vestnik MGTU. Murmansk, 2015;18(4):641–646.Kargin V.S., Pyatigorskaya N.V., Brkich G.E. Various properties of chitosan and the possibility of its use in the medical field. Interuniversity Scientific Congress “Higher School: Scientific Research”. Moscow. 2020:72–78.Kargin V.S., Pyatigorskaya N.V., Brkich G.E. Various properties of chitosan and the possibility of its use in the medical fi eld. Interuniversity Scientifi c Congress “Higher School: Scientifi c Research”. Moscow. 2020:72–78.Horst M.N., Walker A.N., Klar E. The pathway of crustacean chitin synthesis, the Crustacean Integument: Morphology and Biochemistry. Eds. Horst M.N., Free man J.A. CRC: Boca Raton, USA. 1993:113–149.Horst M.N., Walker A.N., Klar E. The pathway of crustacean chitin synthesis, the Crustacean Integument: Morphology and Biochemistry. Eds. Horst M.N., Free man J.A. CRC: Boca Raton, USA. 1993:113–149.Немцев С.В. Комплексная технология хитина и хитозана из панциря ракообразных. Москва: ВНИРО, 2006;134.Nemtsev S.V. Complex technology of chitin and chitosan from the shell of crustaceans. Moscow: VNIRO, 2006;134. (In Russian)].Немцев С.В., Зуева О.Ю., Хисматуллин М.Р., Албулов А.И., Варламов В.П. Получение хитина и хитозана из медоносных пчел. Прикладная биохимия и микробиология. 2006;40:46‒50.Nemtsev S.V., Zuyeva O.Yu., Khismatullin M.R., Albulov A.I., Varlamov V.P. Prikladnaya biokhimiya i mikrobiologiya. 2006; 40:46‒50. (In Russian)].Tereshina, V.M., Memorskaya, A.S., Feofilova, E.P., Nemtsev, D.V., Kozlov, V.M. Isolation of polysaccharide complexes from mycelial fungi and determination of their deacetylation degree. Microbiology. 1997;66:84‒89.Tereshina, V.M., Memorskaya, A.S., Feofi lova, E.P., Nemtsev, D.V., Kozlov, V.M. Isolation of polysaccharide complexes from mycelial fungi and determination of their deacetylation degree. Microbiology. 1997;66:84‒89.Ruiz Herrera J., Gonzalez Prieto J.M., Ruiz Medrano R. Evolution and phylogenetic relationships of chitin synthases from yeasts and fungi. FEMS Yeast Research. 2002;1:247–256. DOI: 10.1111/j.1567-1364.2002.tb00042.xRuiz Herrera J., Gonzalez Prieto J.M., Ruiz Medrano R. Evolution and phylogenetic relationships of chitin synthases from yeasts and fungi. FEMS Yeast Research. 2002;1:247–256. DOI: 10.1111/j.1567-1364.2002.tb00042.xTsigos I., Nathalie Z., Aggeliki M., Alain D., Bouriotis V. Mode of action of chitin deacetylase from Mucor rouxii on N-acetylchitooligosaccharides. European Journal of Biochemistry. 1999;261:1–9. DOI: 10.1046/j.1432-1327.1999.00311.xTsigos I., Nathalie Z., Aggeliki M., Alain D., Bouriotis V. Mode of action of chitin deacetylase from Mucor rouxii on N acetylchitooligosaccharides. European Journal of Biochemistry. 1999;261:1–9. DOI: 10.1046/j.1432-1327.1999.00311.xФеофилова Е.П. Ключевая роль хитина в образовании клеточной стенки грибов, Хитин и хитозан. Получение, свойства и применение. Под ред. Скрябина К.Г., Вихоревой Г.А., Варламова В.П. Москва. Наука. 2002;79–99.Feofilova Ye.P. The key role of chitin in the formation of the cell wall of fungi. Chitin and chitosan. obtaining, properties and application. Skryabin K.G., Vikhoreva G.A., Varlamov V.P., editors. Moscow. Nauka. 2002;79–99. (In Russian)]Феофилова Е.П. Хитин грибов: распространение, биосинтез, физикохимические свойства и перспектива использования. Хитин и хитозан. Получение, свойства и применение. Под ред. Скрябина К.Г., Вихоревой Г.А., Варламова В.П. М. Наука. 2002;100–111.Feofilova Ye.P. Chitin of fungi: distribution, biosynthesis, physico-chemical properties and prospects of use. Chitin and chitosan. Obtaining, properties and application. Skryabin K.G., Vikhoreva G.A., Varlamov V.P., editors. Moscow. Nauka, 2002;100– 111. (In Russian)].Mysyakina I.S., Bokareva D.A., Usov A.I., Feofilova E.P. Differences in the carbohydrate composition between the yeastlike and mycelial cells of Mucor hiemalis. Microbiology. 2012;81:405‒408. DOI: 10.1134/S0026261712040133Mysyakina I.S., Bokareva D.A., Usov A.I., Feofi lova E.P. Diff erences in the carbohydrate composition between the yeastlike and mycelial cells of Mucor hiemalis. Microbiology. 2012;81:405‒408. DOI: 10.1134/S0026261712040133Karimi K., Zamani A. Mucor indicus: biology and industrial application perspectives: a review. Biotechnology Advances. 2013;31:466–481. DOI: 10.1016/j.biotechadv.2013.01.009Karimi K., Zamani A. Mucor indicus: biology and industrial application perspectives: a review. Biotechnology Advances. 2013;31:466– 481. DOI: 10.1016/j.biotechadv.2013.01.009Варламов В.П. Хитин/хитозан и его производные: фундаментальные и прикладные аспекты. Под ред. В.П. Варламова, А.В. Ильина, Б.Ц. Шагдарова. Успехи биологической химии. Москва. 2020;60:317–368.Varlamov V.P. Chitin/chitosan and its derivatives: fundamental and applied aspects. V.P. Varlamova, A.V. Il’ina, B.TS. Shagdarova, editors. Advances in biological chemistry. Moscow. 2020;60:317–368. (In Russian)]/Осовская И.И. Дополнительные главы технологии полимерных материалов. Физико-химические свойства хитина, хитозана и волокон на их основе: учеб. пособие. Под ред. И.И. Осовской. Санкт-Петербург. ВШТЭ СПбГУПТД; 2021:80. ISBN 987-5-91646-263-0.Osovskaya I.I. Additional chapters of polymer materials technology. Physico-chemical properties of chitin, chitosan and fi bers based on them: study manual. Osovskaya I.I., editors. Saint-Petersburg. VSHT·E SPBGUPTD. 2021:80. ISBN 987-5-91646-263-0 (In Russian)].Солдатова С.Ю. Разработка технологии получения хитозана из панцирьсодержащего сырья. Вестник Нижневартовского государственного университета. 2015;1:48–56.Soldatova S.Y. Development of technology for obtaining chitosan from shell-containing raw materials. Vestnik Nizhnevartovskogo gosudarstvennogo universiteta. 2015;1:48–56. (In Russian)].Быков В.П., Сныткин И.И., Быкова В.М., Кривошеина Л.И., Недосекова Т.М., Новиков А.В., Панов К.Н., Фурман Д.И. Всероссийский научно-исследовательский институт рыбного хозяйства и океанографии, патентообладатели. Способ получения хитозана из ракообразных. Российская Федерация Патент RU 2116733. 10 июля 1998 г.Bykov V.P., Snytkin I.I., Bykova V.M., Krivosheina L.I., Nedosekova T.M., Novikov A.V., Panov K.N., Furman D.I. All-Russian Scientifi c Research Institute of Fisheries and Oceanography, assignees. Russian Federation patent RU 2116733. 1998 Jul 10. (In Russian)].Федосов П.А. Хитозан как полимер будущего и перспективы его применения в медицине. Электронный научный журнал «Аpriori». Cерия: естественные и технические науки». Воронеж, 2014;4:1–7. URL: https://cyberleninka.ru/article/n/hitozan-kak-polimer-buduschegoi-perspektivy-ego-primeneniya-v-meditsine/viewerFedosov P.A. Chitosan as a polymer of the future and prospects of its application in medicine. “Electronic scientifi c journal «Аpriori». Series: Natural and technical sciences”. Voronezh. 2014;4:1–7 (In Russian)]. [Electronic resource]. URL: https://cyberleninka.ru/article/n/hitozan-kak-polimer-buduschegoi-perspektivy-ego-primeneniya-v-meditsine/viewer (accessed 17.10.2023).Козырева Е.В., Абрамов А.Ю., Шиповская А.Б. Особенности физикохимических свойств растворов хитозана. Известия Саратовского университета. Новая серия. Серия: Химия. Биология. Экология. 2011;11(2):25–31.Kozyreva YE.V., Abramov A.Yu., Shipovskaya A.B. Features of physico-chemical properties of chitosan solution. News of Saratov University. A new series. Series: Chemistry. Biology. Ecology. 2011;11(2):25–31 (In Russian)].Никитенко П., Хрустицкая Л. Хитозан — полимер будущего. Наука и инновация. 2013;9(127):14–17.Nikitenko P., Khrustitskaya L. Chitosan — polymer of the future. Nauka i innovatsiya. 2013;9(127):14–17 (In Russian)].Сливкин Д.А., Лапенко В.Л., Сафонова О.А., Суслина С.Н., Беленова А.С. Хитозан для фармации и медицины. Вестник Воронежского государственного университета. Серия: Химия. Биология. Фармация. 2011;2:214–232.Slivkin D., Lapenko V.L., Safonova O.A., Suslina S.N., Belenova A.S. Chitosan for pharmacy and medicine. Bulletin of the Voronezh State University. Series: Chemistry. Biology. Pharmacy. 2011;2:214–232 (In Russian)].Албулов А.И., Фролова М.А., Буханцев А.В., Быкова В.М., Немцев С.В. Хитозансодержащие биологически активные добавки к пище в рационализации питания населения. Рыбпром: технологии и оборудование для переработки водных биоресурсов. 2010;2:25–28.Albulov A.I., Frolova M.A., Buhantsev A.V., Bykova V.M., Nemtsev S.V. Chitosan-containing biologically active food additives in rationalizing the nutrition of the population. Rybprom: technologies and equipment for processing aquatic biological resources. 2010;2:25–28 (In Russian)].Гладышев Д.Ю. Строение и фракционный состав карбоксиметилового эфира хитозана. Высокомолекулярные соединения. 1990;32Б(7):503–505.Gladyshev D.YU. Structure and fractional composition of chitosan carboxymethyl ether. Vysokomolekulyarn·yye soyedineniya. 1990;32В(7):503–505 (In Russian)].Камская В.Е. Хитозан: структура, свойства и использование. Научное обозрение. Биологические науки. 2016;6:36–42. URL: https://science-biology.ru/ru/article/view?id=1020Kamskaya V.E. Chitosan: structure, properties and use // Nauchnoye obozreniye. Biologicheskiye nauki. 2016;6:36–42. (In Russian)]. [Ele ctronic resource]. URL: https://science-biology.ru/ru/article/view?id=1020 (accessed: 11.10.2023).Большаков И.Н., Насибов С.М., Куклин Е.Ю. Использование хитозана и его продуктов при воспалительных заболеваниях желудочно-кишечного тракта. Хитин и хитозан. Получение, свойства и применение. Под ред. К.Г. Скрябина, Г.А. Вихревой, В.П. Варламова. Москва. Изд. «Наука», 2006:7–23.Bol’shakov I.N., Nasibov S.M., Kuklin E.Yu. The use of chitosan and its pro ducts in infl ammatory diseases of the gastrointestinal tract. Chitin and chitosan. Receipt, properties and application. Edited by K.G. Scriabin, G.A. Vikhreva, V.P. Varlamov. Moscow: Publishing House «Nauka». 2006:7–23 (In Russian)].Tarsi R., Muzzarelli R., Guzman C., Pruzzo C. Inhibition of Streptococus mutans. Adsorption of hydroxyapatite by low-molecular weight chitosans. J. Dent. Research. 1997;76(2):665–672. DOI: 10.1177/00220345970760020701Tarsi R., Muzzarelli R., Guzman C., Pruzzo C. Inhibition of Streptococus mutans. Adsorption of hydroxyapatite by low-molecular weight chitosans. J. Dent. Research. 1997;76(2):665–672. DOI: 10.1177/00220345970760020701Аbilova G., Makhayeva, D., Irmukhametova, G., Khutoryanskiy, V. Chitosan based hydrogels and their use in medicine. Chemical Bulletin of Kazakh National University. 2020;97(2):16–28. DOI: 10.15328/cb1100Аbilova G., Makhayeva, D., Irmukhametova, G., Khutoryanskiy, V. Chitosan based hydrogels and their use in medicine. Chemical Bulletin of Kazakh National University. 2020;97(2):16–28. DOI: 10.15328/cb1100Tyliszczak B., Drabczyk A., Kudłacik-Kramarczyk S., Bia likWąs K., Kijkowska R., Sobczak-Kupiec A. Preparation and cytotoxicity of chitosan-based hydrogels modified with silver nanoparticles. Colloids and Surfaces B: Biointerfaces. 2017;160:325–330. DOI: 10.1016/j.colsurfb.2017.09.044Tyliszczak B., Drabczyk A., Kudłacik-Kramarczyk S., Bia likWąs K., Kijkowska R., Sobczak-Kupiec A. Preparation and cytotoxicity of chitosan-based hydrogels modifi ed with silver nanoparticles. Colloids and Surfaces B: Biointerfaces. 2017;160:325–330. DOI: 10.1016/j.colsurfb.2017.09.044Deepachitra R., Pujitha Lakshmi R., Sivaranjani K., Helan Chandra J., Sastry T.P. Nanoparticles embedded biomaterials in wound treatment: A review. Journal of Chemical and Pharmaceutical Sciences. 2015;8(2):324–329.Deepachitra R., Pujitha Lakshmi R., Sivaranjani K., Helan Chandra J., Sastry T.P. Nanoparticles embedded biomaterials in wound treatment: A review. Journal of Chemical and Pharmaceutical Sciences. 2015;8(2):324–329.Горшенин Д.С., Жернов Ю.В., Кривцов Г.Г., Хаитов М.Р. Применение хитозана и его производных в иммунотерапии злокачественных новообразований. Иммунология. 2020;41(5): 470-478. DOI: 10.33029/0206-4952-2020-41-5-470-478Gorshenin D.S., Zhernov Yu.V., Krivtsov G.G., Khaitov M.R. The use of chitosan and its derivatives in immunotherapy of malignant neoplasms. Immunologiya. 2020;41(5): 470-478. (In Russian)]. DOI: 10.33029/0206-4952-2020-41-5-470-478Sun B., Yu S., Zhao D., Guo S., Wang X., Zhao K. Polysaccharides as vaccine adjuvants. Vaccine. 2018;36(35):5226–34. DOI: 10.1016/j.vaccine.2018.07.040Sun B., Yu S., Zhao D., Guo S., Wang X., Zhao K. Polysaccharides as vaccine adjuvants. Vaccine. 2018;36(35):5226–34. DOI: 10.1016/j.vaccine.2018.07.040Vasconcelos D.P., de Torre-Minguela C., Gomez A.I. 3D chitosan scaffolds impair NLRP3 inflammasome response in macrophages. Acta Biomater. 2019;91:123–34. DOI: 10.1016/j.actbio.2019.04.035Vasconcelos D.P., de Torre-Minguela C., Gomez A.I. 3D chitosan scaff olds impair NLRP3 infl ammasome response in macrophages. Acta Biomater. 2019;91:123–34. DOI: 10.1016/j.actbio.2019.04.035Fong D., Gregoire-Gelinas P., Cheng A.P. Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages. Biomaterials. 2017;129:127–38. DOI: 10.1016/j.biomaterials.2017.03.022Fong D., Gregoire-Gelinas P., Cheng A.P. Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the infl ammasome in macrophages. Biomaterials. 2017;129:127–38. DOI: 10.1016/j.biomaterials.2017.03.022Pogorielov M. V., Sikora V.Z. Chitosan as a Hemostatic Agent: Current State. European Journal of Medicine. Series B. 2015;1(2):24–33. DOI: 10.13187/ejm.s.b.2015.2.24Pogorielov M. V., Sikora V.Z. Chitosan as a Hemostatic Agent: Current State. European Journal of Medicine. Series B. 2015;1(2):24– 33. DOI: 10.13187/ejm.s.b.2015.2.24Huang Y., Feng L., Zhang Y., He L., Wang C., Xu J., Wu J., Kirk T.B., Guo R., Xue W. Hemostasis mechanism and applications of N-alkylated chitosan sponge. Polymers for Advanced Technologies. 2017;9(28):1107–1114. DOI: 10.3390/md16080273Huang Y., Feng L., Zhang Y., He L., Wang C., Xu J., Wu J., Kirk T.B., Guo R., Xue W. Hemostasis mechanism and applications of N-alkylated chitosan sponge. Polymers for Advanced Technologies. 2017;9(28):1107–1114. DOI: 10.3390/md16080273Будко Е.В., Черникова Д.А., Ямпольский Л.М., Яцюк В.Я. Местные гемостатические средства и пути их совершенствования. Российский медикобиологический вестник имени академика И.П. Павлова. 2019;27(2):274-285. DOI: 10.23888/PAVLOVJ2019272274-285Budko Ye.V., Chernikova D.A., Yampol’skiy L.M., Yatsyuk V.YA. Local hemostatic agents and ways to improve them. Rossiyskiy medikobiologicheskiy vestnik imeni akademika I.P. Pavlova. 2019;27(2):274-285 (In Russian)]. DOI: 10.23888/PAVLOVJ2019272274-285Феськов А.Э., Соколов А.С., Солошенко С.В. Новый гемостатический бинт на основе естественного биополимера хитозана. Харьковская медицинская академия постдипломного образования. Медицина неотложных состояний. 2017;2(81):95–98.Fes’kov A.E., Sokolov A.S., Soloshenko S.V. A new hemostatic bandage based on the natural biopolymer chitosan. Kharkiv Medical Academy of Postgraduate Education. Meditsina neotlozhnykh sostoyaniy. 2017;2(81):95–98 (In Russian)].Ляпина Л.А., Григорьева М.Е., Ляпин Г.Ю., Оберган Т.Ю., Шубина Т.А. Агрегационные эффекты хитозана в крови. Norwegian Journal of development of the International Science. 2021;61:13–16Lyapina L.A., Grigoryeva M.E., Lyapin G.Yu., Obergan T.Yu., Shubina T.A. Aggregation eff ects of chitosan in the blood. Norwegian Journal of development of the International Science. 2021;61:13–16 (In Russian)].Липатов В.А., Бордунова М.А., Панов А.А., Денисов А.А. К вопросу классификации местных кровоостанавливающих средств. Innova. 2022;4(29):38–41.Lipatov V.A., Bordunova M.A., Panov A.A., Denisov A.A. On the issue of classifi cation of local hemostatic agents. Innova. 2022;4(29):38–41 (In Russian)].Sudheesh Kumar P.T., Lakshmanan V.K., Anilkumar T.V., Ramya C., Reshmi P. Flexible and microporous chitosan hydrogel/ nano ZnO composite bandages for wound dressing: In vitro and in vivo evaluation. ACS Applied Materials and Interfaces. 2012;4(5):2618–2629. DOI: 10.1021/am300292vSudheesh Kumar P.T., Lakshmanan V.K., Anilkumar T.V., Ramya C., Reshmi P. Flexible and microporous chitosan hydrogel/ nano ZnO composite bandages for wound dressing: In vitro and in vivo evaluation. ACS Applied Materials and Interfaces. 2012;4(5):2618–2629. DOI: 10.1021/am300292vHu Z., Zhang D.-Y., Lu S.-T., Li P.-W., Li S.-D. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Marine Drugs. 2018;8(16):273. DOI: 10.3390/md16080273Hu Z., Zhang D.-Y., Lu S.-T., Li P.-W., Li S.-D. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Marine Drugs. 2018;8(16):273. DOI: 10.3390/md16080273Kumar S.M.P. Local hemostatic agents in the management of bleeding in oral surgery. Asian Journal Pharmaceutical and Medical Research. 2016;9 (3):35–41.Kumar S.M.P. Local hemostatic agents in the management of bleeding in oral surgery. Asian Journal Pharmaceutical and Medical Research. 2016;9 (3):35–41.Будко Е.В., Черникова Д.А., Ямпольский Л.М., Яцюк В.Я. Местные гемостатические средства и пути их совершенствования. Российский медико-биологический вестник имени академика И.П. Павлова. 2019;27(2):274–285. DOI: 10.23888/PAVLOVJ2019272274-285Budko E.V., Chernikova D.A., Yampolsky L.M., Yatsyuk V.Ya. Local hemostatic agents and ways of their improvement. Rossiyskiy mediko-biologicheskiy vestnik imeni akademika I.P. Pavlova. 2019;27(2): 274– 285. (In Russian)]. DOI: 10.23888/PAVLOVJ2019272274-285Li Q., Lu F., Zhou G., Yu K., Lu B., Xiao Y., Dai F., Wu D., Lan G. Silver Inlaid with Gold Nanoparticle/Chitosan Wound Dressing Enhances Antibacterial Activity and Porosity, and Promotes Wound Healing. Biomacromolecules. 2017;11(18):3766–3775. DOI: 10.1021/acs.biomac.7b01180Li Q., Lu F., Zhou G., Yu K., Lu B., Xiao Y., Dai F., Wu D., Lan G. Silver Inlaid with Gold Nanoparticle/Chitosan Wound Dressing Enhances Antibacterial Activity and Porosity, and Promotes Wound Healing. Biomacromolecules. 2017;11(18):3766–3775. DOI: 10.1021/acs.biomac.7b01180Fan L., Yang H., Yang J., Peng M., Hu J. Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings. Carbohydrate Polymers. 2016;146:427–434. DOI: 10.1016/j.carbpol.2016.03.002Fan L., Yang H., Yang J., Peng M., Hu J. Preparation and characterization of chitosan/gelatin/PVA hydrogel for wound dressings. Carbohydrate Polymers. 2016;146:427–434. DOI: 10.1016/j.carbpol.2016.03.002Hu Z., Zhang D.-Y., Lu S.-T., Li P.-W., Li S.-D. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Marine Drugs. 2018;8(16):273. DOI: 10.3390/md16080273Hu Z., Zhang D.-Y., Lu S.-T., Li P.-W., Li S.-D. Chitosan-Based Composite Materials for Prospective Hemostatic Applications. Marine Drugs. 2018;8(16):273. DOI: 10.3390/md16080273Siemer S., Lahme S., Altziebler S., Machtens S., Strohmaier W., Wechsel H.-W., Goebell P., Schmeller N., Oberneder R., Stolzenburg J.-U., Becker H., Lüftenegger W., Tetens V., Poppel H. Efficacy and Safety of TachoSil® as Haemostatic Treatment versus Standard Suturing in Kidney Tumour Resection: A Randomised Prospective Study. European Urology. 2007;4(52):1156–1163. DOI: 10.1016/j.eururo.2007.04.027Siemer S., Lahme S., Altziebler S., Machtens S., Strohmaier W., Wechsel H.-W., Goebell P., Schmeller N., Oberneder R., Stolzenburg J.-U., Becker H., Lüftenegger W., Tetens V., Poppel H. Effi cacy and Safety of TachoSil® as Haemostatic Treatment versus Standard Suturing in Kidney Tumour Resection: A Randomised Prospective Study. European Urology. 2007;4(52):1156–1163. DOI: 10.1016/j.eururo.2007.04.027Zhang J., Xue S., Zhu X., Zhao Y., Chen Y., Tong J., Shi X., Du Y., Zhong Z., Ye Q. Emerging chitin nanogels/rectorite nanocomposites for safe and effective hemorrhage control. Journal of Materials Chemistry B. 2019;33(7):5096–5103. DOI: 10.1039/c9tb01019jZhang J., Xue S., Zhu X., Zhao Y., Chen Y., Tong J., Shi X., Du Y., Zhong Z., Ye Q. Emerging chitin nanogels/rectorite nanocomposites for safe and eff ective hemorrhage control. Journal of Materials Chemistry B. 2019;33(7):5096–5103. DOI: 10.1039/c9tb01019jSun X., Tang Z., Pan M., Wang Z., Yang H., Liu H. Chitosan/kaolin composite porous microspheres with high hemostatic efficacy. Carbohydrate Polymers. 2017;177:135–143. DOI: 10.1016/j.carbpol.2017.08.131Sun X., Tang Z., Pan M., Wang Z., Yang H., Liu H. Chitosan/kaolin composite porous microspheres with high hemostatic effi cacy. Carbohydrate Polymers. 2017;177:135–143. DOI: 10.1016/j.carbpol.2017.08.131Gudmund Skjå k-Braek, Thorleif Anthonsen, Paul Sandford. Chitin and chitosan. Sources, chemistry, biochemistry, physical properties and applications. London, New York, 1989:835.Gudmund Skjå k-Braek, Thorleif Anthonsen, Paul Sandford. Chitin and chitosan. Sources, chemistry, biochemistry, physical properties and applications. London, New York, 1989:835.Xi Lu., Prudhommeaux F., Meunier A., Sedel L., Guillemin G. Effect of chitosan on rat knee cartilages. Biomaterials. 1999;20:1937–1944. DOI: 10.1016/s0142-9612(99)00097-6Xi Lu., Prudhommeaux F., Meunier A., Sedel L., Guillemin G. Eff ect of chitosan on rat knee cartilages. Biomaterials. 1999;20:1937–1944. DOI: 10.1016/s0142-9612(99)00097-6Suh I.K.F., Matthew H. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials. 2000;21:2589–2598. DOI: 10.1016/s0142-9612(00)00126-5Suh I.K.F., Matthew H. Application of chitosan- based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials. 2000;21:2589–2598. DOI: 10.1016/s0142-9612(00)00126-5Anisha B.S., Biswas R., Chennazhi K.P., Jayakumar R. Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds. International Journal of Biological Macromolecules. 2013;62:310–320. DOI: 10.1016/j.ijbiomac.2013.09.011Anisha B.S., Biswas R., Chennazhi K.P., Jayakumar R. Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds. International Journal of Biological Macromolecules. 2013;62:310–320. DOI: 10.1016/j.ijbiomac.2013.09.011Ishihara M., Ono K., Sato M., Nakanishi K., Saito Y., Yura H., Matsui T., Hattori H., Fujita M., Kikuchi M., Kurita A. Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel. Wound Repair and Regeneration. 2001;9(6):513–521. DOI: 10.1046/j.1524-475x.2001.00513.xIshihara M., Ono K., Sato M., Nakanishi K., Saito Y., Yura H., Matsui T., Hattori H., Fujita M., Kikuchi M., Kurita A. Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel. Wound Repair and Regeneration. 2001;9(6):513–521. DOI: 10.1046/j.1524-475x.2001.00513.xObara K., Ishihara M., Ishizuka T., Fujita M., Ozeki Y., Maehara T., Saito Y., Yura H., Matsui T., Hattori H., Kikuchi M., Kurita A. Photocrosslinkable chitosan hydrogel containing fibroblast growth factor-2 stimulates wound healing in healing-impaired db/db mice. Biomaterials. 2003;24(20):3437–3444. DOI: 10.1016/s0142-9612(03)00220-5Obara K., Ishihara M., Ishizuka T., Fujita M., Ozeki Y., Maehara T., Saito Y., Yura H., Matsui T., Hattori H., Kikuchi M., Kurita A. Photocrosslinkable chitosan hydrogel containing fi broblast growth factor-2 stimulates wound healing in healing-impaired db/db mice. Biomaterials. 2003;24(20):3437–3444. DOI: 10.1016/s0142-9612(03)00220-5Caló E., Barros J.M.S.D., Fernández-Gutiérrez M., San Román J., Ballamy L., Khutoryanskiy V. V. Antimicrobial hydrogels based on autoclaved poly (vinyl alcohol) and poly (methyl vinyl ether-alt-maleic anhydride) mixtures for wound care applications. RSC Advances. 2016;6(60):55211–55219. DOI: 10.1039/C6RA08234CCaló E., Barros J.M.S.D., Fernández-Gutiérrez M., San Román J., Ballamy L., Khutoryanskiy V. V. Antimicrobial hydrogels based on autoclaved poly (vinyl alcohol) and poly (methyl vinyl ether-alt-maleic anhydride) mixtures for wound care applications. RSC Advances. 2016;6(60):55211–55219. DOI: 10.1039/C6RA08234CЯхкинд М.И., Таранцева К.Р. Наносистемы для доставки лекарств из носа в мозг. Известия ПГПУ им. В.Г. Белинского. 2012;29:293–300.Yakhkind M.I., Tarantseva K.R. Nanosystems for drug delivery from the nose to the brain. Izvestiya PGPU im. V.G. Belinskogo. 2012;29:293–300 (In Russian)].Muzzarelli R., Biagini G., Pugnaloni A., Filippini O., Baldassarre V., Castaldini С., Rizzoli С. Reconstruction of paradontal tissue with chitosan. Biomaterials. 1989;10(11):598–603. DOI: 10.1016/0142-9612(89)90113-0Muzzarelli R., Biagini G., Pugnaloni A., Filippini O., Baldassarre V., Castaldini С., Rizzoli С. Reconstruction of paradontal tissue with chitosan. Biomaterials. 1989;10(11):598–603. DOI: 10.1016/0142-9612(89)90113-0Костеша Н.Я. Противолучевая активность препаратов хитозана с растительными экстрактами. Под ред. Н.Я. Костеша. Библиотека ВНИРО. 2006:1–3.Kostesha N.Ya. Anti-radiation activity of chitosan preparations with plant extracts. N.Ya. Kostesha, editors. Biblioteka VNIRO. 2006:1–3. (In Russian)]. [Electronic resource]. URL: http://hdl.handle.net/123456789/2461Bumgardner J.D., Wiser R., Elder S.H., Jouett R. Contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium. J. Biomater. Sci. Polym. Ed. 2003;14:1401–1409. DOI: 10.1163/156856203322599734Bumgardner J.D., Wiser R., Elder S.H., Jouett R. Contact angle, protein adsorption and osteoblast precursor cell attachment to chitosan coatings bonded to titanium. J. Biomater. Sci. Polym. Ed. 2003;14:1401–1409. DOI: 10.1163/156856203322599734Bumgardner J.D., Wiser R., Gerard P.D., Bergin P., Chestnutt B., Marini M., Ramsey V., Elder St.H., Gilbert J.A. Chitosan: potential use as a bioactive coating for orthopaedic and craniofacial/dental implants. J. Biomater. Sci. Polym Ed. 2003;14:423–438. DOI: 10.1163/156856203766652048Bumgardner J.D., Wiser R., Gerard P.D., Bergin P., Chestnutt B., Marini M., Ramsey V., Elder St.H., Gilbert J.A. Chitosan: potential use as a bioactive coating for orthopaedic and craniofacial/dental implants. J. Biomater. Sci. Polym Ed. 2003;14:423–438. DOI: 10.1163/156856203766652048Wang J., de Boer J., de Groot K. Preparation and characterization of electrodeposited calcium phosphate/chitosan coating on Ti6Al4V plates. J. Dent. Res. 2004;83:296–301. DOI: 10.1177/154405910408300405Wang J., de Boer J., de Groot K. Preparation and characterization of electrodeposited calcium phosphate/chitosan coating on Ti6Al4V plates. J. Dent. Res. 2004;83:296–301. DOI: 10.1177/154405910408300405Wang X., Ma J., Wang Y., He B. Bone repair in radii and tibias of rabbits with phosphorylated chitosan reinforced calcium phosphate cements. Biomaterials. 2002;23:4167–4176. DOI: 10.1016/S0142-9612(02)00153-9Wang X., Ma J., Wang Y., He B. Bone repair in radii and tibias of rabbits with phosphorylated chitosan reinforced calcium phosphate cements. Biomaterials. 2002;23:4167–4176. DOI: 10.1016/S0142-9612(02)00153-9Muzzarelli R., Biagini G., Bellardini M., Simonelli L., Castaldini C. and Fratto G. Osteoconduction exerted by methylpyrrolidinone chitosan used in dental surgery. Biomaterials. 1993;14(1):39–43. DOI: 10.1016/0142-9612(93)90073-BMuzzarelli R., Biagini G., Bellardini M., Simonelli L., Castaldini C. and Fratto G. Osteoconduction exerted by methylpyrrolidinone chitosan used in dental surgery. Biomaterials. 1993;14(1):39–43. DOI: 10.1016/0142-9612(93)90073-BCho B.C., Park J.W., Baik B.S., Kwon I.Ch., Kim I.S. The role of hyaluronic acid, chitosan, and calcium sulfate and their combined effect on early bony consolidation in distraction osteogenesis of a canine model. J. Craniofac. Surg. 2002;13:783–793. DOI: 10.1097/00001665-200211000-00014Cho B.C., Park J.W., Baik B.S., Kwon I.Ch., Kim I.S. The role of hyaluronic acid, chitosan, and calcium sulfate and their combined eff ect on early bony consolidation in distraction osteogenesis of a canine model. J. Craniofac. Surg. 2002;13:783–793. DOI: 10.1097/00001665-200211000-00014Kim S.B., Kim Y.J., Yoon T.L., Park S.A. The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. Biomaterials. 2004;25:5715–23. DOI: 10.1016/j.biomaterials.2004.01.022Kim S.B., Kim Y.J., Yoon T.L., Park S.A. The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. Biomaterials. 2004;25:5715–23. DOI: 10.1016/j.biomaterials.2004.01.022Kawakami T., Antoh M., Hasegawa H., Yamagishi T., Ito M., Eda S. Experimental study on osteoconductive properties of a chitosan-bonded hydroxyapatite self-hardening paste. Biomaterials. 1992;13:759–763. DOI: 10.1016/0142-9612(92)90014-fKawakami T., Antoh M., Hasegawa H., Yamagishi T., Ito M., Eda S. Experimental study on osteoconductive properties of a chitosan-bonded hydroxyapatite self-hardening paste. Biomaterials. 1992;13:759–763. DOI: 10.1016/0142-9612(92)90014-fXu H.H., Quinn J.B., Takagi S., Chow L.C. Synergistic reinforcement of in situ hardening calcium phosphate composite scaffold for bone tissue engineering. Biomaterials. 2004;25:1029–1037. DOI: 10.1016/s0142-9612(03)00608-2Xu H.H., Quinn J.B., Takagi S., Chow L.C. Synergistic reinforcement of in situ hardening calcium phosphate composite scaff old for bone tissue engineering. Biomaterials. 2004;25:1029–1037. DOI: 10.1016/s0142-9612(03)00608-2Ito M. In vitro properties of a chitosan-bonded hydroxyapatite bone-filling paste. Biomaterials. 1991;12(1):41–45. DOI: 10.1016/0142-9612(91)90130-3Ito M. In vitro properties of a chitosan-bonded hydroxyapatite bone-fi lling paste. Biomaterials. 1991;12(1):41–45. DOI: 10.1016/0142-9612(91)90130-3Murugan R., Ramakrishna R. Bioresorbable composite bone paste using polysaccharide based nanohydroxyapatite. Biomaterials. 2004;25:3829–3835. DOI: 10.1016/j.biomaterials.2003.10.016Murugan R., Ramakrishna R. Bioresorbable composite bone paste using polysaccharide based nanohydroxyapatite. Biomaterials. 2004;25:3829–3835. DOI: 10.1016/j.biomaterials.2003.10.016Tarsi R., Muzzarelli R. Guzman C, Pruzzo C. Inhibition of Streptococus mutans. Adsorption of hydroxyapatite by low-molecular weight chitosans. J. Dent. Research. 1997;76(2):665–672. DOI: 10.1177/00220345970760020701Tarsi R., Muzzarelli R. Guzman C, Pruzzo C. Inhibition of Streptococus mutans. Adsorption of hydroxyapatite by low-molecular weight chitosans. J. Dent. Research. 1997;76(2):665–672. DOI: 10.1177/00220345970760020701Anraku M., Fujii T., Furutani N., Kadowaki D., Maruyama T., Otagiri M., Gebicki J.M., Tomida H. Antioxidant effects of a dietary supplement: Reduction of indices of oxidative stress in normal subjects by water soluble chitosan. Food and Chemical Toxicology. 2009;47:104–109. DOI: 10.1016/j.fct.2008.10.015Anraku M., Fujii T., Furutani N., Kadowaki D., Maruyama T., Otagiri M., Gebicki J.M., Tomida H. Antioxidant eff ects of a dietary supplement: Reduction of indices of oxidative stress in normal subjects by water soluble chitosan. Food and Chemical Toxicology. 2009;47:104–109. DOI: 10.1016/j.fct.2008.10.015Chang S.H., Wu C.H., Tsai G.J. Effects of chitosan molecular weight on its antioxidant and antimutagenic properties. Carbohydrate Polymers. 2018;181:1026–1032. DOI: 10.1016/j.carbpol.2017.11.047Chang S.H., Wu C.H., Tsai G.J. Eff ects of chitosan molecular weight on its antioxidant and antimutagenic properties. Carbohydrate Polymers. 2018;181:1026–1032. DOI: 10.1016/j.carbpol.2017.11.047Tomida H., Fujii T., Furutani N., Michihara A., Yasufuku T., Akasaki, K., Maruyama, T., Otagiri, M., Gebicki, J.M., Anraku, M. Antioxidant properties of some different molecular weight chitosans. Carbohydrate Research. 2009;344:1690–1696. DOI: 10.1016/j.carres.2009.05.006Tomida H., Fujii T., Furutani N., Michihara A., Yasufuku T., Akasaki, K., Maruyama, T., Otagiri, M., Gebicki, J.M., Anraku, M. Antioxidant properties of some diff erent molecular weight chitosans. Carbohydrate Research. 2009;344:1690–1696. DOI: 10.1016/j.carres.2009.05.006Zou P., Yang X., Wang J., Li Y., Yu H., Zhang Y., Liu G. Advances in characterisation and biological activities of chitosan and chitosan oligosaccharides. Food Chemistry. 2016;190:1174–1181. DOI: 10.1016/j.foodchem.2015.06.076Zou P., Yang X., Wang J., Li Y., Yu H., Zhang Y., Liu G. Advances in characterisation and biological activities of chitosan and chitosan oligosaccharides. Food Chemistry. 2016;190:1174–1181. DOI: 10.1016/j.foodchem.2015.06.076Xia W., Liu P., Zhang J., Chen J. Biological activities of chitosan and chitooligosaccharides. Food Hydrocolloids. 2011;25:170–179. DOI: 10.1016/j.foodhyd.2010.03.003Xia W., Liu P., Zhang J., Chen J. Biological activities of chitosan and chitooligosaccharides. Food Hydrocolloids. 2011;25:170–179. DOI: 10.1016/j.foodhyd.2010.03.003Liu H.T., Li W.M., Xu G., Li X.Y., Bai X.F., Wei P., Yu C., Du Y.G. Chitosan oligosaccharides attenuate hydrogen peroxideinduced stress injury in human umbilical vein endothelial cells. Pharmacologi cal Research. 2009;59:167–175. DOI: 10.1016/j.phrs.2008.12.001Liu H.T., Li W.M., Xu G., Li X.Y., Bai X.F., Wei P., Yu C., Du Y.G. Chitosan oligosaccharides attenuate hydrogen peroxideinduced stress injury in human umbilical vein endothelial cells. Pharmacologi cal Research. 2009;59:167–175. DOI: 10.1016/j.phrs.2008.12.001Li K., Xing R., Liu S., Li R., Qin Y., Meng X., Li P. Separation of chito oligomers with several degrees of polymerization and study of their antioxidant activity. Carbohydrate Polymers. 2012;88:896–903. DOI: 10.1016/j.carbpol.2012.01.033Li K., Xing R., Liu S., Li R., Qin Y., Meng X., Li P. Separation of chito oligomers with several degrees of polymerization and study of their antioxidant activity. Carbohydrate Polymers. 2012;88:896– 903. DOI: 10.1016/j.carbpol.2012.01.033Hu Q., Luo Y. Polyphenol chitosan conjugates: Synthesis, characterization, and applications. Carbohydrate Polymers. 2016;151:624–639. DOI: 10.1016/j.carbpol.2016.05.109Hu Q., Luo Y. Polyphenol chitosan conjugates: Synthesis, characterization, and applications. Carbohydrate Polymers. 2016;151:624– 639. DOI: 10.1016/j.carbpol.2016.05.109Azuma K., Osaki T., Minami S., Okamoto Y. Anticancer and anti-inflammatory properties of chitin and chitosan oligosaccharides. J. Funct. Biomater. 2015; 6(1):33–49. DOI: 10.3390/jfb6010033Azuma K., Osaki T., Minami S., Okamoto Y. Anticancer and anti-infl ammatory properties of chitin and chitosan oligosaccharides. J. Funct. Biomater. 2015; 6(1):33–49. DOI: 10.3390/jfb6010033Huang R., Mendis E., Rajapakse N., Kim S.-K. Strong electronic charge as an important factor for anticancer activity of chitooligosaccharides (COS). Life Sci. 2006;78(20):2399–2408. DOI: 10.1016/j.lfs.2005.09.039Huang R., Mendis E., Rajapakse N., Kim S.-K. Strong electronic charge as an important factor for anticancer activity of chitooligosaccharides (COS). Life Sci. 2006;78(20):2399–2408. DOI: 10.1016/j.lfs.2005.09.039Xu W., Jiang, C., Kong X., Liang Y., Rong M., Liu W. Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses. Mol. Med. Rep. 2012;6(2):385–390. DOI: 10.3892/mmr.2012.918Xu W., Jiang, C., Kong X., Liang Y., Rong M., Liu W. Chitooligosaccharides and N-acetyl-D-glucosamine stimulate peripheral blood mononuclear cell-mediated antitumor immune responses. Mol. Med. Rep. 2012;6(2):385–390. DOI: 10.3892/mmr.2012.918Janes K.A., Fresneau M.P., Marazuela A. Chitosan nanoparticles as delivery systems for doxorubicin. J. Control Released. 2001;73(2–3):255–267. DOI: 10.1016/s0168-3659(01)00294-2Janes K.A., Fresneau M.P., Marazuela A. Chitosan nanoparticles as delivery systems for doxorubicin. J. Control Released. 2001;73(2– 3):255–267. DOI: 10.1016/s0168-3659(01)00294-2Shanmugsundaram N., Ravichandran P., Reddy P.N., Ramamurty N., Pal S., Rao K.P. Collagen-chitosan polymeric scaffold for the in vitro culture of human epidermoid carcinoma cells. Biomaterials. 2001;2:1943–1951. DOI: 10.1016/s0142-9612(00)00220-9Shanmugsundaram N., Ravichandran P., Reddy P.N., Ramamurty N., Pal S., Rao K.P. Collagen-chitosan polymeric scaff old for the in vitro culture of human epidermoid carcinoma cells. Biomaterials. 2001;2:1943–1951. DOI: 10.1016/s0142-9612(00)00220-9

The authors declare that there are no conflicts of interest present.