Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação
Autor(a) principal: | |
---|---|
Data de Publicação: | 2008 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/3871 |
Resumo: | Clavulanic acid is a potent inhibitor of many β-lactamase enzymes producing bacteria, which attribute bacterial resistant against cephalosporins and penicillins. The combination of CA with amoxicillin is the most successful example, that clavulanic acid have the ability to enhance the effectives of β-lactam antibiotic, which was β-lactamase sensitive, allowing the use of amoxicillin in treatment of a lot of diseases. Clavulanic acid is obtained by a fermentation method from various microorganisms belonging to many Streptomyces strains such as Streptomyces clavuligerus. CA itself is an unstable hygroscopic oil which is not used for the preparation of pharmaceutical compounds, for this suitable salts are more appropriated. Among these compounds potassium clavulante is the most stable compound which is normally used for pharmaceutical preparations. In the present work a precipitation of potassium clavulanate starting from the clavulanic acid present in the fermentation broth (cultivated at DEQ-UFSCar) was proposed. Therefore were necessary preliminary studies such as the characterization, monitoramment, standardization of CA (Clavulin®) and improvement of the previously purification steps employed before precipitation step. The directly precipitation (R0) which occurred the reaction of CA with potassium 2-ethyl hexanoate resulting in the potassium clavulante and the precipitation with an intermediate step which occurred an previously reaction of CA with the t-octylamine (R1) allowing a formation of a amine salt of CA (stable intermediate) that afterward it was reacted with the potassium 2-ethyl hexanoate for the formation of potassium clavulanate (R2) were evaluated. The studied reactions were optimized through by response surface methodology (experimental design) in order to permit maximize the yield and to evaluate the stability of the potassium clavulanate precipitated. The results obtained were excellent and demonstrated that the reaction of precipitation employed is very appropriate to be used as the final stage of the process of AC purification from fermentation broth, allowing to obtain a raised yield of the potassium clavulanate associated to a high purity. |
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Hirata, Daniela BattagliaHokka, Carlos Osamuhttp://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4787343E6http://lattes.cnpq.br/5292381247624407c9df7857-118f-4045-853f-69c75ba582942016-06-02T19:55:24Z2009-10-262016-06-02T19:55:24Z2008-08-29HIRATA, Daniela Battaglia. Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação. 2008. 195 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2008.https://repositorio.ufscar.br/handle/ufscar/3871Clavulanic acid is a potent inhibitor of many β-lactamase enzymes producing bacteria, which attribute bacterial resistant against cephalosporins and penicillins. The combination of CA with amoxicillin is the most successful example, that clavulanic acid have the ability to enhance the effectives of β-lactam antibiotic, which was β-lactamase sensitive, allowing the use of amoxicillin in treatment of a lot of diseases. Clavulanic acid is obtained by a fermentation method from various microorganisms belonging to many Streptomyces strains such as Streptomyces clavuligerus. CA itself is an unstable hygroscopic oil which is not used for the preparation of pharmaceutical compounds, for this suitable salts are more appropriated. Among these compounds potassium clavulante is the most stable compound which is normally used for pharmaceutical preparations. In the present work a precipitation of potassium clavulanate starting from the clavulanic acid present in the fermentation broth (cultivated at DEQ-UFSCar) was proposed. Therefore were necessary preliminary studies such as the characterization, monitoramment, standardization of CA (Clavulin®) and improvement of the previously purification steps employed before precipitation step. The directly precipitation (R0) which occurred the reaction of CA with potassium 2-ethyl hexanoate resulting in the potassium clavulante and the precipitation with an intermediate step which occurred an previously reaction of CA with the t-octylamine (R1) allowing a formation of a amine salt of CA (stable intermediate) that afterward it was reacted with the potassium 2-ethyl hexanoate for the formation of potassium clavulanate (R2) were evaluated. The studied reactions were optimized through by response surface methodology (experimental design) in order to permit maximize the yield and to evaluate the stability of the potassium clavulanate precipitated. The results obtained were excellent and demonstrated that the reaction of precipitation employed is very appropriate to be used as the final stage of the process of AC purification from fermentation broth, allowing to obtain a raised yield of the potassium clavulanate associated to a high purity.O ácido clavulânico (AC) é um potente inibidor de certas β-lactamases produzidas por bactérias resistentes às penicilinas e cefalosporinas. A combinação do AC com a amoxicilina é o exemplo de maior sucesso do uso de um antibiótico β-lactâmico sensível a β- lactamase juntamente com um inibidor desta enzima, permitindo assim que a amoxicilina continue sendo efetiva no tratamento de muitas doenças. É produzido via fermentação por linhagens do Streptomyces e dentre estas se encontra o Streptomyces clavuligerus. O ácido clavulânico é um óleo altamente instável e higroscópico, não sendo viável a sua utilização em medicamentos nessa forma, mas sim na sua forma de sal, mais especificamente a de clavulanato de potássio, na qual apresenta maior estabilidade. Assim no presente trabalho foi proposto a precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação, cultivado no DEQ-UFSCar. Para tanto foram necessários estudos preliminares como a caracterização, monitoramento e padronização do AC (Clavulin®) e também o melhoramento das etapas de purificação empregadas anteriormente a etapa da precipitação. Foram avaliadas a reação direta (R0), na qual ocorreu a precipitação do AC com o 2-etilexanoato de potássio, e a reação indireta, com a passagem por um intermediário estável, na qual ocorreu a precipitação do AC com a t-octilamina (R1), formando um sal de amina do AC (intermediário estável) que posteriormente foi reagido com o 2-etilexanoato de potássio para a formação de clavulanato de potássio (R2). As reações estudadas foram otimizadas através da análise por superfície de resposta (planejamento fatorial) de forma a maximizar o rendimento além de avaliar a estabilidade do clavulanato de potássio precipitado. Foram obtidos excelentes resultados que demonstraram que a reação de precipitação empregada é adequada para ser utilizada como a etapa final do processo de purificação do AC proveniente do caldo de fermentação, permitindo a obtenção do clavulanato de potássio com bom rendimento associado a uma pureza elevada.application/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Engenharia Química - PPGEQUFSCarBRPrecipitaçãoÁcido clavulânicoClavulanato de potássioAminaCristalizaçãoENGENHARIAS::ENGENHARIA QUIMICAPrecipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentaçãoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-1-1618b744e-45bb-477d-8c08-82d7196af797info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL2034.pdfapplication/pdf8108586https://repositorio.ufscar.br/bitstream/ufscar/3871/1/2034.pdfd4e20d9750cebd7ff8374a74f5005c00MD51THUMBNAIL2034.pdf.jpg2034.pdf.jpgIM Thumbnailimage/jpeg6782https://repositorio.ufscar.br/bitstream/ufscar/3871/2/2034.pdf.jpg58f6347b435185c101f0a2f72fcb3bd9MD52ufscar/38712023-09-18 18:30:58.036oai:repositorio.ufscar.br:ufscar/3871Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:30:58Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
title |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
spellingShingle |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação Hirata, Daniela Battaglia Precipitação Ácido clavulânico Clavulanato de potássio Amina Cristalização ENGENHARIAS::ENGENHARIA QUIMICA |
title_short |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
title_full |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
title_fullStr |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
title_full_unstemmed |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
title_sort |
Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação |
author |
Hirata, Daniela Battaglia |
author_facet |
Hirata, Daniela Battaglia |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/5292381247624407 |
dc.contributor.author.fl_str_mv |
Hirata, Daniela Battaglia |
dc.contributor.advisor1.fl_str_mv |
Hokka, Carlos Osamu |
dc.contributor.advisor1Lattes.fl_str_mv |
http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4787343E6 |
dc.contributor.authorID.fl_str_mv |
c9df7857-118f-4045-853f-69c75ba58294 |
contributor_str_mv |
Hokka, Carlos Osamu |
dc.subject.por.fl_str_mv |
Precipitação Ácido clavulânico Clavulanato de potássio Amina Cristalização |
topic |
Precipitação Ácido clavulânico Clavulanato de potássio Amina Cristalização ENGENHARIAS::ENGENHARIA QUIMICA |
dc.subject.cnpq.fl_str_mv |
ENGENHARIAS::ENGENHARIA QUIMICA |
description |
Clavulanic acid is a potent inhibitor of many β-lactamase enzymes producing bacteria, which attribute bacterial resistant against cephalosporins and penicillins. The combination of CA with amoxicillin is the most successful example, that clavulanic acid have the ability to enhance the effectives of β-lactam antibiotic, which was β-lactamase sensitive, allowing the use of amoxicillin in treatment of a lot of diseases. Clavulanic acid is obtained by a fermentation method from various microorganisms belonging to many Streptomyces strains such as Streptomyces clavuligerus. CA itself is an unstable hygroscopic oil which is not used for the preparation of pharmaceutical compounds, for this suitable salts are more appropriated. Among these compounds potassium clavulante is the most stable compound which is normally used for pharmaceutical preparations. In the present work a precipitation of potassium clavulanate starting from the clavulanic acid present in the fermentation broth (cultivated at DEQ-UFSCar) was proposed. Therefore were necessary preliminary studies such as the characterization, monitoramment, standardization of CA (Clavulin®) and improvement of the previously purification steps employed before precipitation step. The directly precipitation (R0) which occurred the reaction of CA with potassium 2-ethyl hexanoate resulting in the potassium clavulante and the precipitation with an intermediate step which occurred an previously reaction of CA with the t-octylamine (R1) allowing a formation of a amine salt of CA (stable intermediate) that afterward it was reacted with the potassium 2-ethyl hexanoate for the formation of potassium clavulanate (R2) were evaluated. The studied reactions were optimized through by response surface methodology (experimental design) in order to permit maximize the yield and to evaluate the stability of the potassium clavulanate precipitated. The results obtained were excellent and demonstrated that the reaction of precipitation employed is very appropriate to be used as the final stage of the process of AC purification from fermentation broth, allowing to obtain a raised yield of the potassium clavulanate associated to a high purity. |
publishDate |
2008 |
dc.date.issued.fl_str_mv |
2008-08-29 |
dc.date.available.fl_str_mv |
2009-10-26 2016-06-02T19:55:24Z |
dc.date.accessioned.fl_str_mv |
2016-06-02T19:55:24Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
HIRATA, Daniela Battaglia. Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação. 2008. 195 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2008. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/3871 |
identifier_str_mv |
HIRATA, Daniela Battaglia. Precipitação do clavulanato de potássio a partir do ácido clavulânico presente no caldo de fermentação. 2008. 195 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2008. |
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https://repositorio.ufscar.br/handle/ufscar/3871 |
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por |
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Universidade Federal de São Carlos |
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Programa de Pós-Graduação em Engenharia Química - PPGEQ |
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UFSCar |
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BR |
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Universidade Federal de São Carlos |
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