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1.
São Paulo; s.n; s.n; 2022. 129 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1392257

ABSTRACT

O objetivo deste estudo foi desenvolver uma formulação de bebida láctea bubalina probiótica adicionada de polpa de morango, comparando os efeitos do uso do leite de búfala e de vaca na elaboração dos produtos e verificando a possibilidade de suplementação com triptofano nos produtos lácteos probióticos. Como primeira etapa do trabalho, bebidas lácteas probióticas foram elaboradas a partir de leite bubalino e bovino, fermentadas com Streptococcus thermophilus TA040, Lactobacillus bulgaricus LB340 e Lactobacillus acidophilus La5, e formuladas com 0, 25 e 50% de soro em sua formulação. As bebidas foram avaliadas quanto à cinética de fermentação das culturas láticas utilizadas, ao teor de proteína, gordura e sólidos totais não gordurosos, pós-acidificação, viabilidade das culturas fermentadoras e sua capacidade de sobrevivência ao estresse gastrointestinal in vitro. As bebidas lácteas bubalinas apresentaram resultados superiores as bebidas bovinas. O uso do leite de búfala na elaboração das bebidas lácteas promoveu benefícios quanto as culturas láticas presentes nos produtos, exercendo efeito protetivo e influindo na preservação da viabilidade das bactérias ao longo do armazenamento refrigerado e durante a simulação do estresse gastrointestinal in vitro. As bebidas lácteas elaboradas com 25% apresentaram os resultados mais próximos aos obtidos pelos produtos controle, sem adição de soro, sendo selecionadas para a segunda parte do estudo. Nesta etapa, as formulações de bebida láctea com 25% de soro, foram acrescidas de um preparado com polpa de morango e bebidas sem adição da fruta, utilizadas como controle. As bebidas lácteas bubalinas frutadas, apresentaram menor teor de gordura e melhores características reológicas, com maior viscosidade e consistência do que os produtos controle, sem afetar a pós-acidificação, o perfil de ácido graxo, assim como, a viabilidade e a resistência às condições de estresse gastrointestinal in vitro das culturas fermentadoras. A avaliação da possibilidade de suplementar lácteos probióticos com triptofano foi realizada em conjunto com a Universidade de Milão. Para isso, iogurtes probióticos receberam adição de triptofano antes ou após a fermentação, sendo avaliados com relação ao perfil de pós-acidificação, quantidade de triptofano nos produtos, número de células viáveis por plaqueamento e citometria de fluxo ao longo do armazenamento a 25° e 4°C. Complementarmente, a influência da presença do triptofano no crescimento e produção de compostos antimicrobianos pelas culturas láticas, também foi avaliada. A adição de triptofano após a fermentação dos iogurtes, que foram armazenados sob refrigeração (4°C), além de não afetar a pós-acidificação dos produtos, apresentou benefícios quanto a viabilidade L. acidophilus, redução do dano e aumento do número de células vivas, promovendo teor maior do aminoácido nos iogurtes. A presença do triptofano nos meios de cultivo, também influenciou de forma positiva o crescimento de S. thermophilus e L. acidophilus, melhorando o desenvolvimento das bactérias durante a fermentação e influindo em uma maior atividade antilistérica por parte do S. thermophilus. Diante da influência positiva da aplicação do leite de búfala na elaboração das bebidas lácteas, assim como, a adição do triptofano em iogurtes probióticos, a suplementação do aminoácido em bebidas lácteas bubalinas frutadas permitiria a obtenção de um produto funcional, onde seus benefícios estariam relacionados tanto ao consumo do probiótico presente no produto quanto a complementação de triptofano na dieta do consumidor


The aim of this study was to develop a formulation of probiotic buffalo dairy beverage added with strawberry pulp, comparing the effects of using buffalo and cow's milk in the preparation of products and verifying the possibility of tryptophan supplementation in probiotic dairy products. As a first stage of the work, probiotic dairy beverages were made from buffalo and bovine milk, fermented with Streptococcus thermophiles TA040, Lactobacillus bulgaricus LB340 and Lactobacillus acidophilus La5, and formulated with 0, 25 and 50% whey in their formulation. The beverages were evaluated for the fermentation kinetics of the used lactic cultures, the levels of protein, fat and total no fat solids, post-acidification, fermenting cultures viability and their ability to survive gastrointestinal stress in vitro. Buffalo milk use in dairy beverages production promoted benefits regarding the lactic cultures present in the products, exerting a protective effect and influencing the viability preservation of bacteria during the cold storage and simulation of gastrointestinal stress in vitro. Dairy beverages made with 25% whey addition showed results similar to those obtained by the control products, without whey addition, being selected for the second part of the study. In this part, the dairy beverages formulations with 25% whey, were added with a preparation were added with a strawberry pulp preparation and dairy beverages without added fruit, used as a control. Fruity bubaline dairy beverages had lower fat content and better rheological characteristics, with higher viscosity and consistency than control products, without affecting post-acidification, fatty acid profile, as well as viability and resistance to in vitro gastrointestinal condition of fermented cultures. The possibility of supplementing probiotic dairy products with tryptophan was evaluated in partnership with the University of Milan. For this, probiotic yogurts received the addition of tryptophan before or after fermentation, being evaluated in relation to the post-acidification profile, tryptophan amount in the products, viable cell number per plating and flow cytometry during storage at 25°C and 4°C. In addition, the influence of the tryptophan presence on the growth and production of antimicrobial compounds by lactic cultures was also evaluated. The addition of tryptophan after the yogurt fermentation, which were stored under refrigeration (4°C), in addition to not affecting the post-acidification of the products, showed benefits to the viability of L. acidophilus, reduced the damage and increased the number of cells promoting higher amino acid content in yogurts. Tryptophan presence in the culture media also positively influenced the growth of S. thermophiles and L. acidophilus, improving the development of bacteria during fermentation and influencing better antilisteric activity in the part of S. thermophiles. In view of the buffalo milk positive influence observed after the application in dairy beverage preparation, as well as the addition of tryptophan in probiotic yoghurts, amino acid supplementation in fruity buffalo dairy beverages would allow to obtain a functional product, where its benefits would be related both to the consumption of the probiotic present in the product as to the supplementation of tryptophan in the consumer's diet


Subject(s)
Beverages/adverse effects , Milk/adverse effects , Tryptophan/classification , Yogurt , In Vitro Techniques/methods , Buffaloes , Cell Count/instrumentation , Chemistry, Pharmaceutical , Probiotics/classification , Streptococcus thermophilus/metabolism , Lactobacillus delbrueckii/metabolism , Growth and Development , Flow Cytometry/methods , Whey/adverse effects , Fruit , Amino Acids/antagonists & inhibitors , Lactobacillus acidophilus/metabolism
2.
Braz. J. Pharm. Sci. (Online) ; 58: e20012, 2022. tab, graf
Article in English | LILACS | ID: biblio-1394034

ABSTRACT

Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 µg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines


Subject(s)
Perindopril , Oxidative Coupling , Spectrophotometry/methods , Angiotensins/administration & dosage , Pharmaceutical Preparations , Chemistry, Pharmaceutical/classification , Heart Failure
3.
Chinese Journal of Biotechnology ; (12): 1248-1256, 2022.
Article in Chinese | WPRIM | ID: wpr-927779

ABSTRACT

Natural medicinal chemistry is one of the important courses for students in pharmacy majors. Its experimental teaching focuses on fostering comprehensive experimental skills and innovative abilities of undergraduates. Liaoning University has explored ways to promote the experimental teaching of natural drug chemistry based on the graduate employment and practical teaching experience in the past decade. These explorations include three aspects, such as synchronizing experimental teaching with theoretical teaching, fostering students' awareness of experimental safety, and improving experimental teaching methods in natural drug chemistry experiments. The practices showed that the reform has achieved a good effect. A teaching system that can achieve the three expected aspects has been established, which improved the teaching effect and quality of natural medicinal chemistry experimental courses for undergraduates. Furthermore, these explorations may facilitate fostering pharmacy specialists who can meet the opportunities of developing Chinese medicine and natural drug research and meet the requirements of employment.


Subject(s)
Chemistry, Pharmaceutical/education , Humans , Students , Universities
4.
Rev. Pesqui. Fisioter ; 11(1): 11-31, Fev. 2021. ilus
Article in English, Portuguese | LILACS | ID: biblio-1252814

ABSTRACT

INTRODUÇÃO: Existem várias escalas para avaliar as percepções subjetivas e os componentes individuais em indivíduos com osteoartrite (OA) de joelho. Até o momento, não há escalas disponíveis conhecidas para medir o equilíbrio combinado entre mobilidade, AVD e QV em OA de joelho com base na Classificação Internacional de Funcionalidade, Incapacidade e Saúde (CIF). OBJETIVO: Gerar itens e domínios relacionados aos problemas enfrentados pelos indivíduos com OA de joelhos e validar o conteúdo por especialistas. MÉTODOS: Os domínios e itens foram gerados através de pesquisa bibliográfica extensa (ELS) para extrair itens relacionados a equilíbrio, mobilidade, ADL e QV em indivíduos com OA em joelhos baseados na CIF e através de entrevista aprofundada direta (EAD) em 13 pessoas com OA de joelhos e três especialistas. A validação de conteúdo dos domínios e itens gerados foi validada por 10 especialistas por meio da pesquisa Delphi online. O índice mínimo de validação de conteúdo em nível de item (I-CVI) de 0,80 foi considerado para validar os itens identificados e o índice de validação de conteúdo em nível de escala geral (S-CVI) de 0,90 foi fixado para validar os itens gerados para uso no processo de desenvolvimento da escala. RESULTADOS: Os 117 itens gerados por EAD na ELS foram inicialmente agrupados em 18 domínios. A validação de conteúdo pelo método Delphi resultou em uma diminuição para 56 itens agrupados em 14 domínios com SCVI de 0, 93. CONCLUSÃO: O conjunto abrangente de itens de deficiência, limitação de atividade e restrição de participação para indivíduos com OA de joelhos nos domínios propostos foi desenvolvido e o conteúdo validado. Esses itens são recomendados para uso no desenvolvimento de uma nova escala abrangente de índice de osteoartrite do joelho (CKOAI).


INTRODUCTION: There are several scales to evaluate subjective perceptions and individual components in individuals with knee osteoarthritis (IKOA). Till date, no scale is available to measure the combined balance, mobility, ADL and QoL in IKOA based on the International Classification of Functioning, Disability and Health (ICF). OBJECTIVE: The purpose of the study was to generate items and domains related to problems faced by IKOA and to validate the content by experts. METHODS: The domains and items were generated through extensive literature search (ELS) to extract items related to symptoms, balance, mobility, ADL and QoL in IKOA based on the International Classification of Functioning, Disability and Health (ICF) and through in-depth direct interview (IDDI) from 13 IKOA and three experts. The content validation of domains and items generated were validated by 10 experts through online Delphi survey. Minimum itemlevel content validation index (I-CVI) of 0.80 was considered to validate the identified items and the overall scale-level content validation index (S-CVI) of 0.90 was fixed to validate the generated items to use in scale development process. RESULTS: 117 items generated by IDDI and ELS were grouped under 18 domains initially. Content validation by Delphi method resulted in reduction with 56 item pool being grouped under the 14 domains with SCVI is 0.93. CONCLUSION: The comprehensive impairment, activity limitation and participation restriction item pool for IKOA under the proposed domains, have been developed and content validated. These items are recommended for their use in development of new comprehensive knee osteoarthritis index scale (CKOAI).


Subject(s)
Osteoarthritis , Chemistry, Pharmaceutical , Knee
5.
São Paulo; s.n; s.n; 2021. 123 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-1380006

ABSTRACT

Diante das exigências crescentes das agências regulatórias do mundo todo quanto à redução/eliminação de ácidos graxos trans nos alimentos industrializados, bem como da conscientização do consumidor sobre a relação entre alimentação e saúde, o desenvolvimento de alternativas mais saudáveis aos óleos parcialmente hidrogenados e a outras fontes lipídicas com alto grau de saturaçã o se faz necessário. O oleogel, um sistema composto por um óleo preso em uma rede tridimensional formada por um agente estruturante, se apresenta como uma solução promissora. Dentre os diversos agentes estruturantes, as ceras vegetais se destacam por sua excelente capacidade de gelificação de óleos. Contudo, apresentam uma desvantagem sob o aspecto sensorial, pois podem conferir cerosidade e sabor residual desagradável aos alimentos. Com o objetivo de viabilizar o uso das ceras como agentes estruturantes em oleogéis face ao seu excelente desempenho tecnológico, este projeto propõe o estudo e a aplicação de oleogéis à base de óleo de soja (SBO) estruturado com ceras de farelo de arroz (RBW) a 2 e 4 % (m/m) ou carnaúba (CBW) a 3 e 6% (m/m), isoladamente. As matérias-primas foram caracterizadas e o comportamento de gelificação de cada cera foi avaliado por análises de textura por penetração de cone, estabilidade à perda de óleo por centrifugação, energia coesiva por parâmetro de solubilidade de Hansen (HSP) e comportamento de cristalização e fusão por calorimetria exploratória diferencial (DSC). Os resultados mostraram que ambas as ceras são capazes de formar oleogéis estruturalmente estáveis, contudo, o oleogel com 2% de RBW apresentou maior firmeza a 20 °C (190,4 gf/cm2) do que o oleogel com 6% de CBW a 5 °C (186,1 gf/cm2). Ao final de 5 dias, a capacidade de retenção de óleo do oleogel preparado com RBW foi de 100% às concentrações de 2 e 4% (m/m), contra 61 e 99,3% do oleogel elaborado com CBW às concentrações de 3 e 6% (m/m), respectivamente. Esses resultados podem ser explicados pela diferença entre as energias coesivas, ou seja, do grau de interação molecular entre o solvente e o soluto de cada oleogel. De acordo com os resultados de distância, que prevê se o gel formado será forte, fraco ou se não haverá formação de gel, o soluto CBW apresentou menor interação com o óleo (3,3 MPa1/2) do que o soluto RBW (3,7 MPa1/2). Os oleogéis foram aplicados como ingredientes em diferentes formulações de cream cheese, que foram analisados quanto a diferentes parâmetros de textura e esses resultados foram comparados a uma referência comercial. Nenhuma das amostras produzidas obteve resultados de textura estatisticamente iguais aos do cream cheese comercial (CC), o que pode ser explicado pelas diferenças de formulação e processamento dos produtos. Face aos resultados para textura e estabilidade à perda de óleo dos oleogéis de RBW, este agente estruturante apresenta ria maior potencial de aplicação, porém o oleogel CBW6 obteve alta capacidade de retenção de óleo (99,3%) e quando aplicado na formulação de cream cheese (CCBW6) apresentou resultados de firmeza e espalhabilidade mais próximos da amostra de referência, feita com gordura do leite (CMF)


Given the growing demands of regulatory agencies around the world regarding the reduction/elimination of trans fatty acids in processed foods, as well as consumer awareness about the relationship between food and health, the development of healthier alternatives to partially hydrogenated oils and others lipid sources with a high degree of saturation are necessary. Oleogel, a system composed of an oil trapped in a three-dimensional network formed by a structuring agent, presents itself as a promising solution. Among the various structuring agents, vegetable waxes stand out for their excellent oil gelling capacity. However, they have a sensory disadvantage, as they can give waxy and unpleasant aftertaste to foods. Aiming at enabling the use of waxes as structuring agents in oleogels in view of their excellent technological performance, this study proposes the evaluation and application of oleogels based on soybean oil (SBO) structured with rice bran wax (RBW) at 2 and 4% (m/m) or carnauba (CBW) at 3 and 6% (m/m). The raw materials were characterized and the gelling behavior of each wax was evaluated by analysis of texture by cone penetration, stability to oil loss by centrifugation, cohesive energy by Hansen solubility parameter (HSP) and crystallization and melting behavior. by differential scanning calorimetry (DSC). The results showed that both waxes are able to form structurally stable oleogels, however, oleogel with 2% RBW showed greater firmness at 20 °C (190.4 gf/cm2) than oleogel with 6% CBW at 5° C (186.1 gf/cm2). At the end of 5 days, the oil retention capacity of oleogel prepared with RBW was 100% at concentrations of 2 and 4% (m/m), against 61 and 99.3% of oleogel prepared with CBW at concentrations of 3 and 6% (m/m), respectively. These results can be explained by the difference between the cohesive energies, that is, the degree of molecular interaction between the solvent and the solute of each oleogel. According to the distance results, which predicts if the formed gel will be strong, weak or if there will be no gel formation, the CBW solute showed less interaction with the oil (3.3 MPa1/2) than the RBW solute (3 ,7 MPa1/2). Oleogels were applied as ingredients in different cream cheese formulations, which were analyzed for different texture parameters and these results were compared to a commercial reference. None of the samples produced had texture results statistically equal to those of commercial cream cheese (CC), which can be explained by the differences in formulation and processing of the products. Given the results for texture and oil binding capacity of RBW oleogels, this structuring agent would present greater application potential, but CBW6 oleogel obtained high oil biding capacity (99.3%) and when applied in cream cheese formulation (CCBW6) showed firmness and spreadability results closer to the reference sample, made with milk fat (CMF)


Subject(s)
Chemistry, Pharmaceutical , Industrialized Foods , Food/adverse effects , Vegetables , Waxes/pharmacology , Soybean Oil/classification , Calorimetry/methods , Calorimetry, Differential Scanning/methods
6.
J. Health Biol. Sci. (Online) ; 9(1): 1-4, 2021. ilus, tab
Article in English | LILACS | ID: biblio-1352545

ABSTRACT

Introduction: Mucormycosis is an infection caused by the ubiquitous saprophyte fungi with rapid and aggressive progression, especially in immunocompromised patients. Case report: A 57-year-old woman diagnosed with rhino-orbital mucormycosis presented with decreased renal function after treatment with amphotericin B deoxycholate which was discontinued. Renal function improved after amphotericin B lipid-complex, being also treated with itraconazole, and otorhinolaryngological surgery. Conclusion: The use of Amphotericin B deoxycholate may result in adverse effects. In this situation, Amphotericin B lipid formulation is usually the drug of choice.


Introdução: A mucormicose é uma infecção causada por fungos saprófitos com progressão rápida e agressiva, principalmente em pacientes imunocomprometidos. Relato de caso: Uma paciente de 57 anos, do sexo feminine, com diagnóstico de mucormicose rinorbital apresentou diminuição da função renal após tratamento com anfotericina B desoxicolato que foi descontinuada. A função renal foi recuperada após troca da terapia por anfotericina B complexo lipídico, sendo tratada também com itraconazol e cirurgia otorrinolaringológica. Conclusão: O uso de anfotericina B desoxicolato pode resultar em efeitos adversos. Nestas situações a formulação lipídica da anfotericina B é geralmente a droga de escolha.


Subject(s)
Amphotericin B , Mucormycosis , Therapeutics , Pharmaceutical Preparations , Chemistry, Pharmaceutical , Drug-Related Side Effects and Adverse Reactions , Renal Insufficiency , Infections , Lipids
7.
São Paulo; s.n; s.n; 2020. 79 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1292618

ABSTRACT

A crescente rejeição às gorduras saturadas e trans em decorrência de sua associação com doenças cardiovasculares, entre outras desordens metabólicas de diversas naturezas, tem impulsionado o desenvolvimento de alternativas às gorduras tradicionalmente utilizadas nos processamentos de alimentos. Contudo, o grande desafio reside em conferir funcionalidade tecnológica a lipídios ricos em ácidos graxos insaturados, sendo os oleogéis uma abordagem viável e promissora. Os oleogéis são sistemas constituídos por uma base lipídica composta por óleo no estado líquido estruturada por uma rede tridimensional de moléculas com solubilidade limitada em óleos, chamadas de agentes estruturantes. Estudos recentes relataram a influência do tipo de óleo no processo de formação da rede tridimensional de agentes estruturantes e concluíram que o tamanho da cadeia, a polaridade e a viscosidade do óleo podem afetar grandemente a estrutura do oleogel. Diante disto, o objetivo deste estudo é investigar a influência do tipo de óleo em sua estruturação por cera de candelilla, relacionando as propriedades físicas dos oleogéis formados com diversas características físico-químicas dos óleos que os compõem. Para avaliar esta influência, foram selecionadas bases lipídicas de diferentes composições, como triacilgliceróis de cadeia média (MCT), óleo de girassol alto oleico (HOSO), óleo de girassol (SFO), óleo de linhaça (LSO) e os óleos unicelulares ARASCO e DHASCO, para serem estruturados com cera de candelilla nas concentrações de 1,5, 3,0 e 6,0%. De acordo com as correlações de Pearson estabelecidas, houve uma correlação muito forte (r2 =0,948) entre a firmeza e o conteúdo de ácidos graxos saturados dos óleos, o que pode estar relacionado a uma co-cristalização entre a cera e os ácidos graxos saturados, formando uma estrutura mais firme. Uma correlação forte também foi estabelecida entre o tamanho médio das cadeias de ácidos graxos dos óleos, definido pelo índice de saponificação, e a firmeza dos oleogéis (r2 =0,864). A densidade dos óleos também apresentou correlação forte com a firmeza dos oleogéis (r2 =0,858), assim como a viscosidade apresentou uma forte correlação negativa (r2 = -0,818), o que indica que os óleos mais densos e menos viscosos produzem oleogéis mais firmes. Tanto a cera de candelilla pura quanto os oleogéis apresentaram forma polimórfica ß', que equivale à subcélula ortorrômbica, que demonstra que os diferentes óleos não modificaram a microestrutura da rede de cera de candelilla. Os diferentes tipos de óleo exerceram influência sobre o comportamento de fusão dos oleogéis, fator que permitiu associá-lo a um maior conteúdo de gordura sólida a 20 °C e a um maior teor de triacilgliceróis trissaturados, como nos óleos DHASCO e ARASCO. O grau de insaturação dos óleos influenciou o empacotamento da rede estrutural dos oleogéis, o que foi revelado pela menor perda de óleo nos oleogéis com cadeias mais longas, se comparados ao MCT. Por fim, este trabalho contribuiu com a expansão do conhecimento dos sistemas chamados oleogéis, sugerindo que trabalhos futuros pautem as escolhas de matéria-prima para formulação dos oleogéis nas propriedades de seus componentes. Desta forma, maiores avanços poderão ser alcançados nas pesquisas de sistemas coloidais e consequentemente no desenvolvimento de sistemas de alta qualidade nutricional e, ao mesmo tempo, funcionalidade tecnológica adequada


The growing rejection of saturated and trans fats as a result of their association with cardiovascular diseases, among other metabolic disorders of various kinds, has driven the development of alternative systems to substitute fats traditionally used in food processing. However, the big challenge lies in providing technological functionality to lipids rich in unsaturated fatty acids, with oleogels being a viable and promising approach. Oleogels are systems made up of a lipid base composed of oil in a liquid state structured by a threedimensional network of molecules with limited solubility in oils, called oleogelators. Recent studies have reported the influence of the oil type in the formation process of the threedimensional network of oleogelators and concluded that the fatty acid chain length, the polarity and the viscosity of the oil can greatly affect the structure of the oleogel. In view of this, the objective of this study is to investigate the influence of the oil type in its structuring by candelilla wax, relating the physical properties of the formed oleogels with several physicochemical characteristics of the oils that compose them. To evaluate this influence, lipid bases of different compositions were selected, such as medium chain triglycerides (MCT), high oleic sunflower oil (HOSO), sunflower oil (SFO), linseed oil (LSO) and ARASCO and DHASCO single-cell oils, to be structured with candelilla wax in concentrations of 1.5, 3.0 and 6.0% (w/w). According to the Pearson correlations established, there was a very strong correlation (r2 = 0.948) between the firmness and the saturated fatty acid content of the oils, which may be related to a co-crystallization between the wax and the saturated fatty acids, forming a firmer structure. A strong correlation was also established between the average size of the fatty acid chains of the oils, defined by the saponification value, and the oleogel firmness (r2 = 0.864). The density of the oils also showed a strong correlation with the firmness of the oleogels (r2 = 0.858), as well as the viscosity, which showed a strong negative correlation (r2 = -0.818), indicating that oils with higher density and lower viscosity produce firmer oleogels. Both pure candelilla wax and oleogels presented the ß' polymorphic form, which is equivalent to the orthorhombic subcell, demonstrating that the different oils did not modify the microstructure of the candelilla wax network. The different types of oil influenced the melting behavior of oleogels, a factor that allowed it to be associated with a higher solid fat content at 20 °C and a higher content of trisaturated triacylglycerols, as in DHASCO and ARASCO oils. The degree of unsaturation of the oils influenced the packaging of the structural network of oleogels, which was revealed by the higher oil binding capacity in oleogels with longer chains, compared to MCT. Finally, this work contributed to the expansion of knowledge of oleogel systems, suggesting that future work will guide the choices of raw material for formulating oleogels in the properties of their components. Thus, greater advances can be achieved in the research of colloidal systems and, consequently, in the development of high nutritional quality systems allied to adequate technological functionality


Subject(s)
Oils/administration & dosage , Rhizophoraceae/adverse effects , Trans Fatty Acids , Fats/chemistry , Waxes , Chemistry, Pharmaceutical/classification , Product Packaging/instrumentation , Fats , Food/adverse effects
8.
Braz. J. Pharm. Sci. (Online) ; 56: e18502, 2020. tab, graf
Article in English | LILACS | ID: biblio-1249161

ABSTRACT

Considering the importance of an adequate composition of the formulation in the development of stable, safe and effective cosmetic products, experimental design techniques are tools that can optimize the formulation development process. The objective of this study was to develop topical formulations using the Box-Behnken design with response surface methodology and evaluate its physical, sensory and moisturizing properties. The experimental design used in the first step allowed to identify and to quantify the influence of raw materials, as well as the interaction between them. In the second step, the analysis identified the influence of soy lecithin, the phytantriol and capric acid triglyceride and caprylic on the consistency index, stickiness and greasiness and skin hydration. Cetearyl alcohol, dicetyl phosphate and cetyl phosphate 10EO and acrylates/C10-30 alkylacrylate crosspolymer showed effects in rheological parameters. The addition of soy lecithin had significant effects in terms of consistency index, stickiness, oiliness and immediate moisturizing effects. Phytantriol showed effects on increasing consistency index and oiliness sensation. Thus, the experimental design was shown to be an effective tool for research and development of cosmetics, since it allowed the assessment of the individual and interaction effects of raw materials in the responses: rheological parameters, sensory and clinical efficacy.


Subject(s)
Skin , Chemistry, Pharmaceutical/instrumentation , Emulsions/analysis , Cosmetic Technology , Process Optimization/methods , Research Design , Acids/administration & dosage , Acrylates/adverse effects , Treatment Outcome , Cosmetics/analysis , Cosmetic Stability , Methods
9.
Arch. endocrinol. metab. (Online) ; 63(6): 601-607, Nov.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1055017

ABSTRACT

ABSTRACT Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7


Subject(s)
Humans , Child , Adult , Human Growth Hormone/administration & dosage , Growth Disorders/drug therapy , Drug Administration Schedule , Drug Design , Chemistry, Pharmaceutical , Human Growth Hormone/pharmacokinetics , Human Growth Hormone/chemistry , Delayed-Action Preparations
10.
Article in Chinese | WPRIM | ID: wpr-773719

ABSTRACT

The contents of terrestroside B and terrestrosin K in Tribuli Fructus with different degree of stir-frying were determined by high performance liquid chromatography with evaporative light-scattering detector( HPLC-ELSD). The results showed that the contents of terrestroside B and terrestrosin K were increased at first and then decreased,and both of them had the highest content at the best time of heating. The results of simulated processing of Tribulus Terrestris saponins showed that when the processing time kept constant,the contents of terrestroside B and terrestrosin K were decreased gradually with the increase of processing temperature from 180 ℃ to240 ℃. At a certain temperature,the content of terrestrosin K was increased first and then decreased with the prolongation of processing time,and reached the highest level at 5 min. However,the content of terrestroside B was increased first and then decreased with the increase of processing time only at 180 ℃,and reached the highest level at 10 min. When the processing temperature was controlled at200,220 and 240 ℃ respectively,the content of terrestroside B was decreased gradually with the increase of processing time. The simulated processing products of tribuluside A,terrestroside B and terrestrosin K were qualitatively characterized by ultra-performance liquid chromatography-time of flight mass spectrometry( UPLC-TOF/MS). It was proved that tribuluside A and terrestrosin Ⅰ containing C-22-OH were dehydroxylated in the processing of Tribuli Fructus and transformed respectively into terrestroside B and terrestrosin K containing C-20-C-22 double bond. As a result,the contents of terrestroside B and terrestrosin K were increased. The sugar chains at C-3 and C-26 positions of terrestroside B and terrestrosin K could be deglycosylated and converted into monosaccharide chain saponins and short sugar chain saponins,so the contents of terrestroside B and terrestrosin K were reduced. The study provides reference for further revealing the processing principle of Tribuli Fructus.


Subject(s)
Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Fruit , Chemistry , Saponins , Tandem Mass Spectrometry , Tribulus , Chemistry
11.
Article in Chinese | WPRIM | ID: wpr-773718

ABSTRACT

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.


Subject(s)
Chemistry, Pharmaceutical , Curcumin , Chemistry , Drug Stability , Methylcellulose , Chemistry , Polymers , Solubility
12.
Article in Chinese | WPRIM | ID: wpr-773257

ABSTRACT

To establish and validate the design space of the Digeda-4 flavored decoction( DGD-4D) extraction process by using the quality by design( Qb D) concept. With DGD-4D decoction pieces as a model drug,with the transfer rate of aesculin,picroside I,picroside Ⅱ,geniposide and the yield of extract as critical quality attributes( CQAs),the single factor experiment design was used to determine the level of each factor; the Plackett-Burman experiment design was used to select the critical process parameters( CPPs);and the Box-Behnken experiment design was used to optimize the extraction process. The design space of the DGD-4D extraction process was established,and finally,four experimental points were selected to verify the established model. The single factor experiment determined the levels of each factor,including soaking time 60 min and 30 min,water adding volume 12 times and 8 times,extraction time 90 min and 30 min,number of extraction times 3 times and 1 time,as well as extraction temperature 100 ℃ and 90 ℃.By Plackett-Burman experimental design,the DGD-4D water addition,extraction time and number of extraction times were determined to be CPPs. The Box-Behnken experimental variance analysis showed that P of the regression model was less than 0. 01 and the misstated value was more than 0. 01,indicating that the model had good predictive ability,and the operation space of CPPs in the DGD-4D extraction process was determined as follows: the amount of water addition was 10-12 times; extraction time 50-80 min; and number of extraction times was 3 times. The design space of DGD-4D extraction process based on the concept of Qb D is conducive to improving the stability of product quality and laying a foundation for the future development of DGD-4D.


Subject(s)
Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Chemistry , Research Design
13.
HU rev ; 45(3): 254-260, 2019.
Article in Portuguese | LILACS | ID: biblio-1049302

ABSTRACT

Introdução: Dentre os corantes de fontes naturais disponíveis no mercado, os mais comuns são aquelas capazes de conferir as cores vermelha, roxa, laranja e amarela, sendo a coloração azul relativamente escassa. A espécie Ravenala madagascariensis, também conhecida como árvore dos viajantes, é uma planta oriunda da Ilha de Madagascar, África do Sul, característica por sementes recobertas por arilos fibrosos de coloração azul intensa. Objetivo: Descrever uma metodologia capaz de extrair e incorporar os corantes azuis presentes nos arilos em uma formulação dermocosmética estável. Metodologia: Foi realizado screening com distintos líquidos extratores para a obtenção do extrato dos arilos. O extrato em ciclometicone foi incorporado em preparações cosméticas empregando-se as bases Polawax® e Cold cream. Após a avaliação dos aspectos sensoriais, a formulação preparada com Polawax foi direcionada para avaliação de estabilidade acelerada (15 dias) de acordo com o protocolo definido pela ANVISA. Resultados: O melhor processo extrativo foi obtido pela utilização do ciclometicone, que é um excipiente compatível com o preparo de formulações cosméticas. O produto contendo 1% do extrato dos arilos em ciclometicone, incorporado à base Polawax, foi avaliado em relação às variáveis aspecto, cor (azul), odor, sensação ao tato e pH (5,5) e não apresentou alterações no ensaio de estabilidade acelerado. Conclusão: Com a metodologia apresentada, foi possível extrair e preparar uma formulação dermocosmética estável com nova proposta de corante azul, aplicável como excipiente para formulações.


Introduction: Among the dyes from natural sources available in the market, the most common are those capable of giving the colors red, purple, orange and yellow, being the blue coloration relatively scarce. The Ravenala madagascariensis species, also known as the traveler's tree, is a plant from Madagascar Island, South Africa, characterized by seeds covered by intense blue colored fibrous aryls. Objective: To describe a methodology capable of extracting and incorporating the blue dyes present in aryls in a stable dermocosmetic formulation. Methodology:Screening with different extracting liquids was performed to obtain the extract of the arils. The cyclomethicone extract was incorporated into cosmetic preparations using the Polawax® and Cold cream bases. After evaluation of sensory aspects, the formulation prepared with Polawax was directed to accelerated stability evaluation (15 days) according to the protocol defined by ANVISA. Results: The best extraction process was obtained by the use of cyclomethicone, which is an excipient compatible with the preparation of cosmetic formulations. The product containing 1% of the cyclomethicone aryl extract, incorporated into the Polawax base, was evaluated in relation to the variables appearance, color (blue), odor, touch sensation and pH (5.5) and showed no changes in the stability test accelerated. Conclusion:With the methodology presented, it was possible to extract and prepare a stable dermocosmetic formulation with new blue dye proposal, applicable as an excipient for formulations.


Subject(s)
Plants , Chemistry, Pharmaceutical , Color , Cosmetics , Guidelines as Topic , Coloring Agents , Brazilian Health Surveillance Agency , Cosmetic Coloring Agents
14.
Braz. J. Pharm. Sci. (Online) ; 54(4): e17361, 2018. tab, graf
Article in English | LILACS | ID: biblio-1001561

ABSTRACT

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.


Subject(s)
Tretinoin/analysis , Breast Neoplasms/drug therapy , Pharmaceutical Preparations/analysis , Chemistry, Pharmaceutical , Hyaluronic Acid
15.
São Paulo; s.n; s.n; 2018. 90 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-906084

ABSTRACT

A tuberculose (TB) é uma das maiores causas de morte por infecção no mundo, sendo que, em 2015, registraram-se 10,4 milhões de novos casos. O agente etiológico da doença, o Mycobacterium tuberculosis (Mtb), apresenta altos níveis de resistência frente aos quimioterápicos disponíveis para o tratamento da TB. Além disso, a terapia atual da doença explora poucos alvos essenciais ao Mtb. Neste sentido, explorar novos alvos, essenciais ao crescimento e sobrevivência da micobactéria é de grande interesse e poderia gerar fármacos mais efetivos, eficazes contra cepas resistentes e a forma latente da TB. Para este fim, o presente trabalho propôs o desenvolvimento de inibidores da enzima fosfopanteteína adenililtransferase (PPAT), a qual possui caráter regulatório na via de biossíntese da Coenzima A (CoA) da micobactéria. Inicialmente, propuseram-se 50 estruturas de potenciais inibidores da PPAT de M. tuberculosis (MtPPAT), baseando-se na estrutura de seu substrato, a fosfopanteteína, e na estrutura do sítio ativo da enzima. Em seguida, propuseram-se outros 28 ligantes. A fim de se prever as potenciais complementaridades entre os 78 inibidores propostos e o sítio ativo da MtPPAT, empregou-se a estratégia de docking. Posteriormente, realizaram-se cálculos semi-empíricos, com os complexos dos ligantes que se mostraram mais interessantes nas simulações de docking, a fim de se obter informações sobre a entalpia de interação dos ligantes com o sítio ativo da MtPPAT. A partir dos resultados obtidos nos estudos computacionais, selecionaram-se os inibidores que se mostraram mais promissores. A síntese destes ligantes e a de seus fragmentos foi realizada. Avaliaram-se a atividade microbiológica in vitro, bem como a citotoxicidade dos ligantes sintetizados. Alguns dos compostos sintetizados apresentaram atividade frente às cepas sensíveis e resistentes do Mtb na casa de micromolar. Todos os compostos ativos não foram considerados citotóxicos. A fim de validar o planejamento e o alvo dos possíveis inibidores, verificando a atividade inibitória desses frente à enzima MtPPAT, realizou-se a produção e purificação da enzima. Por fim, realizaram-se ensaios de inibição enzimática frente à MtPPAT, os quais permitiram a identificação dos primeiros inibidores da enzima já descritos, com atividade na casa de micromolar, validando-se o alvo em questão


Tuberculosis is one of the major causes of death by infection worldwide. In 2015, 10.4 thousand new cases of the disease were registered. The tuberculosis' causing agent Mycobacterium tuberculosis presents high levels of resistance for the available chemotherapy. Thereof, exploit new M. tuberculosis targets is of utmost importance to overcome drug resistant tuberculosis. In this sense, the enzyme phosphopantetheine adenylyltransferase (PPAT) generates scientific interest since it displays a regulatory role in the M. tuberculosis coenzyme A (CoA) biosynthesis. Therefore, the purpose of the present study was the development of M. tuberculosis PPAT (MtPPAT) inhibitors. Initially, 50 potentially MtPPAT inhibitors were designed based on MtPPAT's substrate and the enzyme's active site. After preliminary results, more 28 compounds were designed. Docking simulations were performed with the 78 compounds synthesized, leading to the prediction of the interaction between the proposed inhibitors and MtPPAT active site. Latelly, semi-empirical calculations were performed with the most promising compounds. These calculations were carried out to obtain information about the enthalpy interactions between compounds and MtPPAT active site. Computational studies led to the selection of the most promising inhibitors. Those compounds and some of their fragments were synthesized, purified, and characterized. The synthesized compounds had their in vitro microbiological activity and cytotoxicity evaluated. Some of the synthesized compounds showed activity against the Mtb sensitive and resistant strains in micromolar range. Besides that, the active compounds were not considered cytotoxic. To validate the potential inhibitors' design and evaluate their capacity to inhibit MtPPAT, the enzyme was produced and purified. MtPPAT inhibitory assays were performed, leading to the first inhibitors of the enzyme, with activity in micromolar range, validating the target


Subject(s)
Tuberculosis/prevention & control , Enzyme Inhibitors/analysis , Chemistry, Pharmaceutical/classification , Coenzyme A , Drug Compounding , Drug Discovery , Mycobacterium tuberculosis/metabolism
16.
São Paulo; s.n; s.n; 2018. 139 p. tab, graf, ilus.
Thesis in Portuguese | LILACS | ID: biblio-997679

ABSTRACT

As neoplasias malignas, doenças mundialmente conhecidas como câncer, possuem um dos tratamentos mais onerosos, tóxicos e de baixa seletividade na terapêutica atual. Adicionalmente, o contínuo crescimento da incidência da doença também representa em uma grande problemática. Os produtos de origem natural se apresentam como alternativas para o tratamento de diversas doenças, incluindo o câncer. A capsaicina, produto natural proveniente das pimentas do gênero Capsicum, apresenta propriedades antineoplásicas, portanto, pode ser utilizada como protótipo para obtenção de análogos. Quatro séries foram planejadas e sintetizadas, obtendo-se compostos ureídicos e tioureídicos. A estratégia sintética se baseou na reação da piperonilamina ou vanililamina com isocianatos ou isotiocianatos, ligados a substituintes aromáticos ou alquílicos. Vinte e sete análogos foram sintetizados com rendimentos variando entre 22 a 90 %. Todos os compostos apresentaram aspecto sólido variando a cor de branco a levemente amarelados. Para a caracterização das substâncias obtidas foram utilizados dados de RMN 1H e 13C, ponto de fusão e a determinação de pureza foi realizada mediante HPLC. Todos os compostos foram submetidos a ensaios de avaliação da atividade citotóxica por redução do MTT contra linhagens de células cancerígenas e células sadias. Os compostos RPF652, RPF 512 - 514) apresentaram atividade comparável ou superior ao protótipo com valores de IC50 na faixa de micromolar. Os resultados apontados pela modelagem molecular indicam que descritores eletrônicos como Ehomo e Elumo podem estar associados à atividade do composto, ClogP (3,92) pode favorecer melhor permeabilidade na membrana celular, e o maior número de sítios de acepção de ligação de hidrogênio podem corroborar com a citotoxidade em linhagem A2058. Particularmente, o análogo RPF652 apresentou atividade pronunciada com valores de IC50 de 55, 67, e 87 µM contra as células A2058, SK-MEL 25, e U87, respectivamente, o que representa atividade de superior à capsaicina. Como uma tendência o composto RPF652 causou parada no ciclo de linhagem B-RAF B16F10 não levando a célula à morte. Porém esta linhagem não apresenta mutação no códon V600E. Em contraponto, o análogo RPF652 apresentou maior potência contra linhagem V600EB-RAF A2058 mutada, indicando possível seletividade em linhagens que apresentam a mutação no códon V600E da proteína B-RAF. Ademais, novos esforços devem ser concentrados no análogo RPF652 para melhor elucidação mecanística de sua atividade


Malignant neoplasms have one of the most expensive, non-selective and toxic treatment of present times. This situation, combined with the rising incidence rate, represents a major problem for humanity. The use of natural products can be an alternative for treatment of several diseases, including cancer. Capsaicin is a natural product derived from Capsicum peppers, with reported anticancer activity and can be used as prototype for the design of new molecules with remarkable activity. Capsaicin analogues were designed and synthesized in four series of derivatives, replacing the prototype amide bond with urea and thiourea functions. The synthetic approach builds the urea/ thiourea scaffold using the reaction of piperonyl/ vanilyl amine with alkyl and aryl isocyanides/ isothiocyanides. Twenty-seven new compounds were obtained with yields from 22 to 90 %, and were fully characterized using 1H and 13C NMR, the purity was determined by melting point and HPLC. All of the obtained compounds were evaluated in MTT cytotoxic assays against different cancer cell-lines (B16F10, A2058, SK-MEL 25 and U-87), and compared with healthy human cells (T75). Additionally, the most active compound was submitted to a cell cycle arrest assay. The thiourea derivative RPF652 was the most active compound, and the urea derivatives RPF512, RPF513 and RPF514 showed good micromolar IC50 values. This results, when correlated with several in silico-calculated properties for the obtained molecules, suggests that ClogP, Ehomo, Elumo and the number of hydrogen-bond acception sites may be correlated to the anticancer activity reported. RPF652 especially, showed IC50 values with superior activity and better selectivity index when compared with capsaicin. The cell-cycle assay of RPF652 showed significant arrest in V600E-codon B-RAF non-mutated cell lines (B16F10) without killing it. V600E-codon B-RAF mutated cells A2058, were significantly more sensitive to the compound. These findings may suggest some insights about the mechanism of action and targets of this compounds


Subject(s)
Drug Screening Assays, Antitumor , Capsaicin/analysis , Antineoplastic Agents/classification , Capsicum/classification , Chemistry, Pharmaceutical/instrumentation , Pimenta/adverse effects , Neoplasms/drug therapy
17.
São Paulo; s.n; s.n; 2018. 123 p. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: biblio-998353

ABSTRACT

A tuberculose (TB) é considerada uma das principais doenças infecciosas e apresenta fatores críticos como a relação com o HIV/AIDS, tratamento longo e a resistência a múltiplos fármacos. A enzima di-hidrofolato redutase das micobactérias (mtDHFR) é um alvo pouco explorado e apresenta grande potencial para o desenvolvimento de novos fármacos contra TB. Estudos preliminares obtiveram fragmentos com baixa afinidade à mtDHFR, entretanto com potencial para otimização. Com isso, o fragmento foi usado como protótipo para a proposição de 22 análogos. Os compostos foram planejados utilizando informações sobre ligantes e a estrutura tridimensional de mtDHFR, além do biososterismo como estratégia norteadora. Os ensaios de docking molecular com a mtDHFR revelaram que os análogos propostos tiveram escores interessantes e, além disso, a inserção de substituintes demonstrou favorecer a ligação à enzima, o que corroborou o planejamento. Com isso, sintetizou-se 22 análogos planejados e o protótipo MB872, por meio de protocolos de alquilação, hidrólise e cicloadição 1,3 dipolar para os compostos com anéis triazol e tetrazol. Os compostos foram obtidos com rendimentos de bom a ótimo (60 ~ 90%) e suas estruturas foram elucidadas por RMN 1H e 13C. Os resultados do ensaio de inibição enzimática corroboraram com os dados de docking, uma vez que a presença do grupo carboxílico revelou ser importante para a atividade. Além disso, alguns dos compostos revelaram atividades interessantes, entre 8 a 40 µM, sendo que o mais ativo apresentou IC50 de 7 µM. Ensaios de cinética enzimática com o análogo mais ativo indicou uma inibição não competitiva com o substrato natural da enzima, uma vez que os valores de Km se mantiveram constantes, enquanto Vmax decaiu (0,22 µM e 0,43 - 0,34 ΔFU/min, respectivamente). Os análogos sintetizados foram mandados para ensaio in vitro para avaliar a atividade frente a micobactéria


Tuberculosis (TB) is an important infectious disease and presents critical factors such as the relationship with HIV / AIDS, long treatment and resistance to multiple drugs. The enzyme dihydrofolate reductase from mycobacteria (mtDHFR) is a poorly explored and presents great potential to be a target for new drugs against TB. Preliminary studies have obtained fragments with low affinity to mtDHFR, but with potential to become lead compounds. Therefore, the fragment was used as a prototype for 22 analogues proposed in this work. The compounds were designed using bioisosterism, information about ligands and the three-dimensional structure of mtDHFR. Molecular docking assays with mtDHFR revealed satisfactory scores for anlogues. Furthermore, the insertion of substituents seemed to increase the affinity with the enzyme. Thereby, twenty two analogues and prototype were synthesized using alkylation, hydrolysiss and 1,3-dipolar cycloaddition methods. The compounds were obtained in good yields (60 ~ 90%) and their structures were elucidated with 1H and 13C NMR spectroscopy. The enzymatic affinity assay corroborates docking results, because the presence of carboxyl group showed to be important for the activity. Furthermore, some of the compounds revealead interesting activities, ranging 8 to 40 µM. The most active showed IC50 of 7 µM and enzyme kinetics assays indicated noncompetitive inhibition with natural enzyme substrate. The synthesized analogs were sent for in vitro assay to assess mycobacteria activity


Subject(s)
Process Optimization , Molecular Docking Simulation/instrumentation , Mycobacterium/classification , Tetrahydrofolate Dehydrogenase/analysis , Tuberculosis/pathology , Chemistry, Pharmaceutical/methods
18.
Article in Chinese | WPRIM | ID: wpr-771735

ABSTRACT

To compare the quality difference between Mahuang Xixin Fuzi decoction(MXF) prepared by traditional decocting method and that prepared by two commonly used decocting methods, and explore the scientific nature of the traditional decocting method. By taking effect-toxic components in MXF as the research object, this article investigated these three different decocting methods from the quantitative determination of effect-toxic components in MXF. By using multivariate statistical analysis methods, three characteristic constituents were identified as kakoul, mesaconitine (MA) and hypaconitine (HA) respectively. As compared with two commonly used decocting methods, MXF decoction prepared by traditional decocting method had the shortest boiling time, but with the lowest dissolution rates of MA and AC and the higher dissolution rates of mono-ester aconitum alkaloids. In addition, the traditional decocting method increased the dissolution of ephedra alkaloid and accelerated the hydrolysis of diester diterpenoid alkaloids. There were differences in the content of effect-toxic components in MXF decoctions prepared by three different decocting methods, which can provide a reference for use of the classical prescriptions.


Subject(s)
Alkaloids , Chemistry , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Reference Standards , Plant Extracts , Chemistry
19.
Article in Chinese | WPRIM | ID: wpr-771707

ABSTRACT

Ginger juice, a commonly used adjuvant for Chinese materia medica, is applied in processing of multiple Chinese herbal decoction pieces. Because of the raw materials and preparation process of ginger juice, it is difficult to be preserved for a long time, and the dosage of ginger juice in the processing can not be determined base on its content of main compositions. Ginger juice from different sources is hard to achieve consistent effect during the processing of traditional Chinese herbal decoction pieces. Based on the previous studies, the freeze drying of ginger juice under different shelf temperatures and vacuum degrees were studied, and the optimized freeze drying condition of ginger juice was determined. The content determination method for 6-gingerol, 8-gingerol, 10-gingerol and 6-shagaol in ginger juice and redissolved ginger juice was established. The content changes of 6-gingerol, 8-gingerol, 10-gingerol, 6-gingerol, 6-shagaol, volatile oil and total phenol were studied through the drying process and 30 days preservation period. The results showed that the freeze drying time of ginger juice was shortened after process optimization; the compositions basically remained unchanged after freeze drying, and there was no significant changes in the total phenol content and gingerol content, but the volatile oil content was significantly decreased(<0.05). Within 30 days, the contents of gingerol, total phenol, and volatile oil were on the decline as a whole. This study has preliminarily proved the feasibility of freeze-drying process of ginger juice as an adjuvant for Chinese medicine processing.


Subject(s)
Adjuvants, Pharmaceutic , Chemistry, Pharmaceutical , Methods , Drugs, Chinese Herbal , Reference Standards , Freeze Drying , Ginger , Chemistry , Materia Medica , Reference Standards
20.
Article in English | WPRIM | ID: wpr-773604

ABSTRACT

Analysis errors can occur in the desorbing process of ginkgo diterpene lactone meglumine injection (GDMI) by a conventional analysis method, due to several factors, such as easily crystallized samples, solvent volatility, time-consuming sample pre-processing, fixed method, and offline analysis. Based on risk management, near-infrared (NIR) and mid-infrared (MIR) spectroscopy techniques were introduced to solve the above problems with the advantage of timely analysis and non-destructive nature towards samples. The objective of the present study was to identify the feasibility of using NIR or MIR spectroscopy techniques to increase the analysis accuracy of samples from the desorbing process of GDMI. Quantitative models of NIR and MIR were established based on partial least square method and the performances were calculated. Compared to NIR model, MIR model showed greater accuracy and applicability for the analysis of the GDMI desorbing solutions. The relative errors of the concentrations of Ginkgolide A (GA) and Ginkgolide B (GB) were 2.40% and 2.89%, respectively, which were less than 5.00%. The research demonstrated the potential of the MIR spectroscopy technique for the rapid and non-destructive quantitative analysis of the concentrations of GA and GB.


Subject(s)
Chemistry, Pharmaceutical , Methods , Reference Standards , Drug Compounding , Reference Standards , Drugs, Chinese Herbal , Chemistry , Reference Standards , Ginkgolides , Chemistry , Reference Standards , Injections , Lactones , Least-Squares Analysis , Meglumine , Chemistry , Reference Standards , Reproducibility of Results , Risk Management , Spectrophotometry, Infrared , Reference Standards
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