Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite

Detalhes bibliográficos
Ano de defesa: 2006
Autor(a) principal: Cunha, Pablyana Leila Rodrigues da
Orientador(a): Feitosa, Judith Pessoa de Andrade
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/2279
Resumo: The viscosupplementation is a therapeutic technique used in the osteoarthritis treatment, in which the sinovial fluid (lubricant of the ligaments) is replaced by viscoelastic solutions derived from hyaluronic acid with rheological properties better than the starting material. This treatment is expensive and commercially, only hialuronic acid is used. The research of other polysaccharides such as the guar gum and chitin, for the application on viscosupplementation, increases the possibility of substituting the hyaluronic acid with other from more abundant sources and more viable. The guar gum (GGNP) was purified through various methods with the aim to reduce contaminants, such as polysaccharides (but not galactomannan) and most importantly, proteins. The method with best efficiency in the reduction of these contaminants was the physic+Fehling method, resulting in a guar (GGFISFEH) with 96% of galactomannan and 0% of proteins. The commercial gum (GGNP) and the purified (GGFISFEH) were crosslinked with glutaraldehyde to originate fluids hydrogel of high viscosity. The increase in viscosity of the polysaccharides with the increase of the crosslinking reaction time is gradual and can be interrupted at the moment a hydrogel fluid is obtained through dialysis against water. The hydrogels obtained have viscosity forty times (GelGGNP) and eight hundred times (GelGGFISFEH) than the initial viscosities of the gums. The purified guar gum (GGFISFEH) was modified through oxidative reaction with a TEMPO reagent and through a sulfatation reaction, with the aim of introducing carboxylated and sulphate groups, making their structure similar to the one from the hyaluronic acid and the chondroitin sulfate. The reactions were efficient in the modification, resulting in degree of substitution (DS) of 0.36 for the oxidated gum (GGOXID) and 0.60 for the sulfated gum(GGSULF). 13C and 1H NMR analyses indicated that the sulfatation occurred in C6 of galactose and the oxidation on C6 of mannose The chitin was carboxylated to form a water soluble polyeletrolite and with a group of acetyl glucosamine similar to the hyaluronic acid. This reaction was tested in various conditions, resulting in different DS. The best yield was of 92% with a DS of 0.53. The pharmacological tests were conducted on rats Wistar. The effect, per si, in the articulate cavity of GGNP and GFISFEH, both in solution and gel was also studied. The GGNP caused incapacitation and dosage-dependant cell influx, an effect not demonstrated by GGFISFEH. The articular incapacitation was greater with the administration of GelGGNP. It was also evaluated the therapeutic effect of GGFISFEH in solution and gel, and Hilano G-F20 in osteoarthritis induced by the transection of the anterior cruciate ligament. The inhibition of the articular incapacitation obtained through gel or through the guar solution were entirely similar to the results obtained with the Hilano G-F20. The guar gum presents potential as a viscosuplemented agent.
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spelling Cunha, Pablyana Leila Rodrigues daFeitosa, Judith Pessoa de Andrade2012-03-12T17:14:25Z2012-03-12T17:14:25Z2006CUNHA, P. L. R. Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite 2006. Tese (Doutorado em Química Orgânica e Inorgânica) – Universidade Federal do Ceará, Fortaleza, 2006.http://www.repositorio.ufc.br/handle/riufc/2279The viscosupplementation is a therapeutic technique used in the osteoarthritis treatment, in which the sinovial fluid (lubricant of the ligaments) is replaced by viscoelastic solutions derived from hyaluronic acid with rheological properties better than the starting material. This treatment is expensive and commercially, only hialuronic acid is used. The research of other polysaccharides such as the guar gum and chitin, for the application on viscosupplementation, increases the possibility of substituting the hyaluronic acid with other from more abundant sources and more viable. The guar gum (GGNP) was purified through various methods with the aim to reduce contaminants, such as polysaccharides (but not galactomannan) and most importantly, proteins. The method with best efficiency in the reduction of these contaminants was the physic+Fehling method, resulting in a guar (GGFISFEH) with 96% of galactomannan and 0% of proteins. The commercial gum (GGNP) and the purified (GGFISFEH) were crosslinked with glutaraldehyde to originate fluids hydrogel of high viscosity. The increase in viscosity of the polysaccharides with the increase of the crosslinking reaction time is gradual and can be interrupted at the moment a hydrogel fluid is obtained through dialysis against water. The hydrogels obtained have viscosity forty times (GelGGNP) and eight hundred times (GelGGFISFEH) than the initial viscosities of the gums. The purified guar gum (GGFISFEH) was modified through oxidative reaction with a TEMPO reagent and through a sulfatation reaction, with the aim of introducing carboxylated and sulphate groups, making their structure similar to the one from the hyaluronic acid and the chondroitin sulfate. The reactions were efficient in the modification, resulting in degree of substitution (DS) of 0.36 for the oxidated gum (GGOXID) and 0.60 for the sulfated gum(GGSULF). 13C and 1H NMR analyses indicated that the sulfatation occurred in C6 of galactose and the oxidation on C6 of mannose The chitin was carboxylated to form a water soluble polyeletrolite and with a group of acetyl glucosamine similar to the hyaluronic acid. This reaction was tested in various conditions, resulting in different DS. The best yield was of 92% with a DS of 0.53. The pharmacological tests were conducted on rats Wistar. The effect, per si, in the articulate cavity of GGNP and GFISFEH, both in solution and gel was also studied. The GGNP caused incapacitation and dosage-dependant cell influx, an effect not demonstrated by GGFISFEH. The articular incapacitation was greater with the administration of GelGGNP. It was also evaluated the therapeutic effect of GGFISFEH in solution and gel, and Hilano G-F20 in osteoarthritis induced by the transection of the anterior cruciate ligament. The inhibition of the articular incapacitation obtained through gel or through the guar solution were entirely similar to the results obtained with the Hilano G-F20. The guar gum presents potential as a viscosuplemented agent.A viscossuplementação é uma técnica terapêutica utilizada no tratamento de osteoartrite, a qual busca substituir o líquido sinovial (lubrificante das articulações) por soluções viscoelásticas de derivados do ácido hialurônico com propriedades reológicas melhores que a deste líquido. Este tratamento é caro e comercialmente só se utilizada o ácido hialurônico. O estudo de outros polissacarídeos, tais como a goma guar e a quitina, para aplicação em viscossuplementação, aumenta a possibilidade de substituir o ácido hialurônico por outros de fontes mais abundantes e viáveis. A goma guar (GGNP) foi purificada por vários métodos com a finalidade de reduzir contaminantes, como polissacarídeos (que não galactomanana) e principalmente proteínas. O método de maior eficiência na redução destes contaminantes foi o método físico+Fehling, resultando em uma guar (GGFISFEH) com 96% de galactomanana e 0% de proteínas. A goma comercial (GGNP) e a purificada (GGFISFEH) foram reticuladas com glutaraldeído para originar hidrogéis fluidos de alta viscosidade. O aumento da viscosidade do polissacarídeo com o tempo de reação de reticulação é gradativo e pode ser interrompido no momento em que se obtém um hidrogel fluido, por diálise contra água. Os hidrogéis obtidos tem viscosidade quarenta vezes (GelGGNP) e oitocentas vezes (GelGGFISFEH) a viscosidade das soluções iniciais das gomas. A goma guar purificada (GGFISFEH) foi modificada por reação de oxidação com reagente TEMPO e por reação de sulfatação, com a finalidade de introduzir grupos carboxilato e sulfato, assemelhando a estrutura desta ao ácido hialurônico e ao condroitim sulfato. As reações foram eficientes na modificação, resultando em grau de substituição (GS) de 0,36 para a goma oxidada (GGOXID) e 0,60 para a sulfatada (GGSULF). Análises de RMN de 13C e 1H indicam que a sulfatação ocorreu no C6 da galactose e a oxidação no C6 da manose. A quitina foi carboximetilada para originar um polieletrólito solúvel em água e com grupo acetil glicosamina semelhante ao do ácido hialurônico. Esta reação foi testada em várias condições reacionais, resultando em GS diferentes. O melhor rendimento foi de 92% com um GS de 0,53. Os testes farmacológicos foram realizados em ratos Wistar. Avaliou-se o efeito per si na cavidade articular de GGNP e GGFISFEH, ambas em solução e gel. A GGNP causou incapacitação e influxo celular dosedependente, efeito não demonstrado por GGFISFEH. A incapacitação articular foi maior com a administração do GelGGNP. Avaliou-se também, o efeito terapêutico da GGFISFEH em solução e gel, e Hilano G-F20 em osteoartrite induzida pelo modelo de transecção do ligamento cruzado anterior. A inibição da incapacitação articular obtida pelo gel ou pela solução de guar foram absolutamente semelhantes ao resultado obtido com o Hilano G-F 20. A goma guar apresenta potencial como agente viscossuplementador.PolissacarídeoOsteoartriteViscossuplementaçãoQuímicaDesenvolvimento de polissacarídeos com ação terapêutica em osteoartriteDevelopment of polysaccharides with therapeutic action in osteoarthristis.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/2279/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52ORIGINAL2006_Te_Pab_Cunha.pdf2006_Te_Pab_Cunha.pdfapplication/pdf5485794http://repositorio.ufc.br/bitstream/riufc/2279/1/2006_Te_Pab_Cunha.pdffd48af2a2681eaaffc79166fdd7ef860MD51riufc/22792020-06-24 11:28:18.974oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-06-24T14:28:18Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
dc.title.en.pt_BR.fl_str_mv Development of polysaccharides with therapeutic action in osteoarthristis.
title Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
spellingShingle Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
Cunha, Pablyana Leila Rodrigues da
Polissacarídeo
Osteoartrite
Viscossuplementação
Química
title_short Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
title_full Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
title_fullStr Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
title_full_unstemmed Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
title_sort Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite
author Cunha, Pablyana Leila Rodrigues da
author_facet Cunha, Pablyana Leila Rodrigues da
author_role author
dc.contributor.author.fl_str_mv Cunha, Pablyana Leila Rodrigues da
dc.contributor.advisor1.fl_str_mv Feitosa, Judith Pessoa de Andrade
contributor_str_mv Feitosa, Judith Pessoa de Andrade
dc.subject.por.fl_str_mv Polissacarídeo
Osteoartrite
Viscossuplementação
Química
topic Polissacarídeo
Osteoartrite
Viscossuplementação
Química
description The viscosupplementation is a therapeutic technique used in the osteoarthritis treatment, in which the sinovial fluid (lubricant of the ligaments) is replaced by viscoelastic solutions derived from hyaluronic acid with rheological properties better than the starting material. This treatment is expensive and commercially, only hialuronic acid is used. The research of other polysaccharides such as the guar gum and chitin, for the application on viscosupplementation, increases the possibility of substituting the hyaluronic acid with other from more abundant sources and more viable. The guar gum (GGNP) was purified through various methods with the aim to reduce contaminants, such as polysaccharides (but not galactomannan) and most importantly, proteins. The method with best efficiency in the reduction of these contaminants was the physic+Fehling method, resulting in a guar (GGFISFEH) with 96% of galactomannan and 0% of proteins. The commercial gum (GGNP) and the purified (GGFISFEH) were crosslinked with glutaraldehyde to originate fluids hydrogel of high viscosity. The increase in viscosity of the polysaccharides with the increase of the crosslinking reaction time is gradual and can be interrupted at the moment a hydrogel fluid is obtained through dialysis against water. The hydrogels obtained have viscosity forty times (GelGGNP) and eight hundred times (GelGGFISFEH) than the initial viscosities of the gums. The purified guar gum (GGFISFEH) was modified through oxidative reaction with a TEMPO reagent and through a sulfatation reaction, with the aim of introducing carboxylated and sulphate groups, making their structure similar to the one from the hyaluronic acid and the chondroitin sulfate. The reactions were efficient in the modification, resulting in degree of substitution (DS) of 0.36 for the oxidated gum (GGOXID) and 0.60 for the sulfated gum(GGSULF). 13C and 1H NMR analyses indicated that the sulfatation occurred in C6 of galactose and the oxidation on C6 of mannose The chitin was carboxylated to form a water soluble polyeletrolite and with a group of acetyl glucosamine similar to the hyaluronic acid. This reaction was tested in various conditions, resulting in different DS. The best yield was of 92% with a DS of 0.53. The pharmacological tests were conducted on rats Wistar. The effect, per si, in the articulate cavity of GGNP and GFISFEH, both in solution and gel was also studied. The GGNP caused incapacitation and dosage-dependant cell influx, an effect not demonstrated by GGFISFEH. The articular incapacitation was greater with the administration of GelGGNP. It was also evaluated the therapeutic effect of GGFISFEH in solution and gel, and Hilano G-F20 in osteoarthritis induced by the transection of the anterior cruciate ligament. The inhibition of the articular incapacitation obtained through gel or through the guar solution were entirely similar to the results obtained with the Hilano G-F20. The guar gum presents potential as a viscosuplemented agent.
publishDate 2006
dc.date.issued.fl_str_mv 2006
dc.date.accessioned.fl_str_mv 2012-03-12T17:14:25Z
dc.date.available.fl_str_mv 2012-03-12T17:14:25Z
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dc.identifier.citation.fl_str_mv CUNHA, P. L. R. Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite 2006. Tese (Doutorado em Química Orgânica e Inorgânica) – Universidade Federal do Ceará, Fortaleza, 2006.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/2279
identifier_str_mv CUNHA, P. L. R. Desenvolvimento de polissacarídeos com ação terapêutica em osteoartrite 2006. Tese (Doutorado em Química Orgânica e Inorgânica) – Universidade Federal do Ceará, Fortaleza, 2006.
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